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Search Results (544)

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Keywords = single-cell transcriptome sequencing

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22 pages, 563 KB  
Review
Transcriptomic Signatures in IgA Nephropathy: From Renal Tissue to Precision Risk Stratification
by Charlotte Delrue and Marijn M. Speeckaert
Int. J. Mol. Sci. 2025, 26(20), 10055; https://doi.org/10.3390/ijms262010055 - 15 Oct 2025
Abstract
IgA nephropathy (IgAN) is the most prevalent type of primary glomerulonephritis, with heterogeneous clinical outcomes. Conventional prognostic factors, such as proteinuria, eGFR, and Oxford histologic classification, have poor sensitivity and specificity. Recently, transcriptomic profiling has been employed to provide insights into the molecular [...] Read more.
IgA nephropathy (IgAN) is the most prevalent type of primary glomerulonephritis, with heterogeneous clinical outcomes. Conventional prognostic factors, such as proteinuria, eGFR, and Oxford histologic classification, have poor sensitivity and specificity. Recently, transcriptomic profiling has been employed to provide insights into the molecular definition of IgAN and facilitate patient stratification in those at risk of disease progression. In this review, we summarize our current understanding of IgAN derived from bulk RNA sequencing, single-cell transcriptomics, spatial transcriptomics, and gene expression profiling to elucidate the molecular characteristics of IgAN. Bulk transcriptomics of glomerular and tubulointerstitial compartments highlighted consistently upregulated genes (e.g., CCL2, CXCL10, LCN2, HAVCR1, COL1A1) and altered pathways (e.g., NF-κB, TGF-β, JAK/STAT, and complement) that are associated with clinical decline. Single-cell and single-nucleus RNA-sequencing has also identified the value of pathogenic cell types and regulatory networks in mesangial cells, tubular epithelium, and immune infiltrates. Furthermore, noninvasive transcriptomic signatures developed from urine and blood may represent useful real-time surrogates of tissue activity. With the advent of integrated analyses and machine learning approaches, personalized risk models that outperform traditional metrics are now available. While challenges remain, particularly related to standardization, cohort size, and clinical deployment, transcriptomics is likely to revolutionize IgAN by providing early risk predictions and precision therapeutics. Unlike prior reviews, our work provides an integrative synthesis across bulk, single-cell, spatial, and noninvasive transcriptomics, linking molecular signatures directly to clinical translation in risk stratification and precision therapeutics. Full article
(This article belongs to the Special Issue Molecular Pathology and Next-Generation Biomarkers in Nephrology)
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20 pages, 5947 KB  
Article
Integrative Single-Cell and Bulk Transcriptomic Analysis Identifies Macrophage-Related Gene Signatures Predictive of Hepatocellular Carcinoma in Cirrhosis 
by Zhongyuan Zhang, Chuisheng Zeng, Xuetong Yong, Wenping Zhou, Yongfang Xie and Jianzhong Shu
Genes 2025, 16(10), 1213; https://doi.org/10.3390/genes16101213 - 15 Oct 2025
Abstract
Background/Objectives: Liver cirrhosis is a major global health challenge and a key risk factor for hepatocellular carcinoma (HCC), a malignancy with high mortality due to late diagnosis. This study aimed to integrate single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk RNA-seq) [...] Read more.
Background/Objectives: Liver cirrhosis is a major global health challenge and a key risk factor for hepatocellular carcinoma (HCC), a malignancy with high mortality due to late diagnosis. This study aimed to integrate single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk RNA-seq) data, using single-cell data to identify macrophage-associated transcriptomic changes during the progression from cirrhosis to HCC, and using bulk data to validate these findings in independent cohorts, while developing predictive models for early risk assessment. Methods: We integrated single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing datasets derived from liver tissues of cirrhosis and HCC patients. Single-cell data were used to identify macrophage subtypes and their dynamic transcriptional changes, while bulk data provided validation in independent cohorts. Gene expression and network analyses were performed, and candidate genes were used to construct diagnostic models with Lasso regression, Random Forest, and Extreme Gradient Boosting (XGBoost). Model performance was evaluated using receiver operating characteristic curves. Results: We identified eleven macrophage-associated genes, among which KLK11, MARCO, CFP, KRT19, GAS1, SOD3, and CYP2C8 were downregulated in HCC, indicating loss of tumor-suppressive and pro-apoptotic functions, while TOP2A, CENPF, MKI67, and NUPR1 were upregulated, reflecting enhanced cell cycle progression, proliferation, and M2 polarization. These are all associated with the progression from liver cirrhosis to HCC. Based on these findings, we established predictive models using Lasso, Random Forest, and XGBoost, which stratified cirrhotic patients into high- and low-risk groups according to cutoff values using liver tissue transcriptomic data. All three models demonstrated high diagnostic performance. Conclusions: This study highlights the critical role of macrophage-associated transcriptomic remodeling in liver disease progression. The machine learning–based predictive models offer a promising approach for early diagnosis and clinical decision-making in patients with cirrhosis. Full article
(This article belongs to the Section Bioinformatics)
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24 pages, 935 KB  
Review
Cancer-Associated Fibroblasts Arising from Endothelial-to-Mesenchymal Transition: Induction Factors, Functional Roles, and Transcriptomic Evidence
by Junyeol Han, Eung-Gook Kim, Bo Yeon Kim and Nak-Kyun Soung
Biology 2025, 14(10), 1403; https://doi.org/10.3390/biology14101403 - 13 Oct 2025
Viewed by 201
Abstract
Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment (TME) that influence cancer progression via extracellular matrix (ECM) remodeling and secretion of growth factors and cytokines. Endothelial-to-mesenchymal transition (EndMT) is emerging as an important axis among the heterogeneous origins of CAFs. This [...] Read more.
Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment (TME) that influence cancer progression via extracellular matrix (ECM) remodeling and secretion of growth factors and cytokines. Endothelial-to-mesenchymal transition (EndMT) is emerging as an important axis among the heterogeneous origins of CAFs. This review introduces the diverse methods used to induce EndMT in cancer—mouse tumor models, conditioned-medium treatment, co-culture, targeted gene perturbation, ligand stimulation, exosome exposure, irradiation, viral infection, and three-dimensional (3D) culture systems—and summarizes EndMT cell-type evidence uncovered using transcriptomic and proteomic technologies. Hallmark EndMT features include spindle-like morphology, increased motility, impaired angiogenesis and barrier function, decreased endothelial markers (CD31, VE-cadherin), and increased mesenchymal markers (α-SMA, FN1). Reported mechanisms include signaling via TGF-β, cytoskeletal/mechanical stress, reactive oxygen species, osteopontin, PAI-1, IL-1β, GSK-3β, HSP90α, Tie1, TNF-α, HSBP1, and NOTCH. Cancer-induced EndMT affects tumors and surrounding TME—promoting tumor growth and metastasis, expanding cancer stem cell-like cells, driving macrophage differentiation, and redistributing pericytes—and is closely associated with poor survival and therapy resistance. Finally, we indicate each study’s stance: some frame cancer-induced EndMT as a source of CAFs, whereas others, from an endothelial perspective, emphasize barrier weakening and promotion of metastasis. Full article
(This article belongs to the Special Issue Recent Advances in Tumor Microenvironment Biology)
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14 pages, 9220 KB  
Article
RNA-Seq and Single-Cell RNA-Seq Analyses of Tilapia Head Kidney in Response to Streptococcus agalactiae and Aeromonas hydrophila
by Qi Li, Zulin Fang, Zhengshuang Li, Xinxian Wei and Youchuan Wei
Animals 2025, 15(20), 2951; https://doi.org/10.3390/ani15202951 - 11 Oct 2025
Viewed by 185
Abstract
High-throughput sequencing has significantly advanced the exploration of fish immune mechanisms, enabling a more detailed understanding of immune responses and their underlying molecular pathways. In this study, we applied comparative transcriptomics and single-cell RNA sequencing to investigate the immune mechanisms of tilapia in [...] Read more.
High-throughput sequencing has significantly advanced the exploration of fish immune mechanisms, enabling a more detailed understanding of immune responses and their underlying molecular pathways. In this study, we applied comparative transcriptomics and single-cell RNA sequencing to investigate the immune mechanisms of tilapia in response to different pathogenic bacteria. Our results demonstrated that nonspecific cytotoxic cells (NCCs) and monocytes/macrophages (Mos/Mφs) mounted the most pronounced responses to both Streptococcus agalactiae and Aeromonas hydrophila infections. Moreover, Mos/Mφs exhibited distinct differentiation patterns depending on the bacterial challenge. Collectively, these findings offer new insights into the antibacterial immune strategies of lower vertebrates. Full article
(This article belongs to the Special Issue Fish Diseases and Healthy Farming)
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28 pages, 4762 KB  
Article
Conditional Ablation of PKCλ/ι in CD4+ T Cells Ameliorates Hepatic Fibrosis in Schistosoma japonicum-Infected Mice via T Follicular Helper (Tfh) Cell Suppression Coupled with Increased Follicular Regulatory T (Tfr) and Regulatory B (Breg) Cell Activities
by Congjin Mei, Yingying Yang, Panpan Dong, Julu Lu, Xinyue Zhang, Jingping Li, Lijun Song and Chuanxin Yu
Biomolecules 2025, 15(10), 1430; https://doi.org/10.3390/biom15101430 - 9 Oct 2025
Viewed by 246
Abstract
To further investigate the role of PKCλ/ι in Schistosoma japonicum-induced hepatic fibrosis, we employed a CD4+ T-cell-specific PKCλ/ι conditional knockout (KOSJ) mouse model, with wild-type (WTSJ) mice used as controls. Transcriptomic profiling of hepatic mRNA was used to reveal the immune [...] Read more.
To further investigate the role of PKCλ/ι in Schistosoma japonicum-induced hepatic fibrosis, we employed a CD4+ T-cell-specific PKCλ/ι conditional knockout (KOSJ) mouse model, with wild-type (WTSJ) mice used as controls. Transcriptomic profiling of hepatic mRNA was used to reveal the immune regulatory mechanisms underlying the role of PKCλ/ι in the hepatic fibrosis caused by S. japonicum infection. Flow cytometry, RT–qPCR and ELISA were used to analyze the effects of PKCλ/ι on Tfh and Tfr cells, and single-cell RNA sequencing was used to elucidate the interactions between Tfr and B cells. The results showed that PKCλ/ι deficiency led to altered BCR signaling gene expression, reduced germinal center activity, and decreased anti-SEA antibody levels. Tfh cells and key factors including IL-21, CXCR5, and ICOS were downregulated, while Tfr cells and IL-10+ B cells increased. Additionally, hepatic neutrophils decreased and Treg/Tfr ratios rose, with enhanced IL-10-mediated cellular crosstalk. These findings indicate that PKCλ/ι deficiency attenuates liver fibrosis by inhibiting Tfh differentiation, promoting Tfr function, and activating IL-10-producing Breg cells, suggesting its potential as a therapeutic target. Full article
(This article belongs to the Section Molecular Medicine)
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41 pages, 1020 KB  
Review
Preclinical Diagnosis of Type 1 Diabetes: Reality or Utopia
by Tatyana A. Marakhovskaya, Dmitry V. Tabakov, Olga V. Glushkova, Zoya G. Antysheva, Yaroslava S. Kiseleva, Ekaterina S. Petriaikina, Nickolay A. Bugaev-Makarovskiy, Anna S. Tashchilova, Vasiliy E. Akimov, Julia A. Krupinova, Viktor P. Bogdanov, Tatyana M. Frolova, Victoria S. Shchekina, Ekaterina S. Avsievich, Valerii V. Gorev, Irina G. Rybkina, Ismail M. Osmanov, Irina G. Kolomina, Igor E. Khatkov, Natalia A. Bodunova, Vladimir S. Yudin, Anton A. Keskinov, Sergey M. Yudin, Pavel Y. Volchkov, Dmitry V. Svetlichnyy, Mary Woroncow and Veronika I. Skvortsovaadd Show full author list remove Hide full author list
Biomedicines 2025, 13(10), 2444; https://doi.org/10.3390/biomedicines13102444 - 7 Oct 2025
Viewed by 348
Abstract
Type 1 Diabetes Mellitus (T1D) is an autoimmune disease characterized by the destruction of pancreatic β-cells, predominantly manifesting in childhood or adolescence. The lack of clearly interpretable biological markers in the early stages, combined with the insidious onset of the disease, poses [...] Read more.
Type 1 Diabetes Mellitus (T1D) is an autoimmune disease characterized by the destruction of pancreatic β-cells, predominantly manifesting in childhood or adolescence. The lack of clearly interpretable biological markers in the early stages, combined with the insidious onset of the disease, poses significant challenges to early diagnosis and the implementation of preventive strategies. The applicability of classic T1D biomarkers for understanding the mechanisms of the autoimmune process, preclinical diagnostics and treatment efficiency is limited. Despite advances in next-generation sequencing (NGS) technologies, which have enabled large-scale genome-wide association studies (GWASs) and the identification of polygenic risk scores (PRSs) associated with T1D predisposition, as well as progress in bioinformatics approaches for assessing dysregulated gene expression, no universally accepted risk assessment model or definitive predictive biomarker has been established. Until now, the use of new promising biomarkers for T1D diagnostics is limited by insufficient evidence base. However, they have great potential for the development of diagnostic methods on their basis, which has been shown in single or serial large-scale studies. This critical review covers both well-known biomarkers widely used in clinical practice, such as HLA-haplotype, non-HLA SNPs, islet antigen autoantibodies, C-peptide, and the promising ones, such as cytokines, cfDNA, microRNA, T1D-specific immune cells, islet-TCR, and T1D-specific vibrational bands. Additionally, we highlight new approaches that have been gaining popularity and have already demonstrated their potential: GWAS, single-cell transcriptomics, identification of antigen-specific T cells using scRNA-seq, and FTIR spectroscopy. Although some of the biomarkers, in our opinion, are still limited to a research context or are far from being implemented in clinical diagnostics of T1D, they have the greatest potential of being applied in clinical practice. When integrated with the monitoring of the classical autoimmune diabetes markers, they would increase the sensitivity and specificity during diagnostics of early and preclinical stages of the disease. This critical review aims to evaluate the current landscape of classical and emerging biomarkers in autoimmune diabetes, with a focus on those enabling early detection—prior to extensive destruction of pancreatic islets. Another goal of the review is to focus the attention of the scientific community on the gaps in early T1D diagnostics, and to help in the selection of markers, targets, and methods for scientific studies on creating novel diagnostic panels. Full article
(This article belongs to the Section Endocrinology and Metabolism Research)
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20 pages, 7178 KB  
Article
Exploring the Abnormal Characteristics of the Ovaries During the Estrus Period of Kazakh Horses Based on Single-Cell Transcriptome Technology
by Wanlu Ren, Jun Zhou, Jianping Zhu, Jianguang Zhang, Xueguang Zhao and Xinkui Yao
Biology 2025, 14(10), 1351; https://doi.org/10.3390/biology14101351 - 2 Oct 2025
Viewed by 219
Abstract
The ovary is among the earliest organs to undergo age-related degeneration, limiting the reproductive potential of elite horses and constraining the growth of the equine industry. Follicular development during estrus is a key determinant of fertility, yet the molecular mechanisms underlying its decline, [...] Read more.
The ovary is among the earliest organs to undergo age-related degeneration, limiting the reproductive potential of elite horses and constraining the growth of the equine industry. Follicular development during estrus is a key determinant of fertility, yet the molecular mechanisms underlying its decline, particularly at the level of specific ovarian cell types, remain poorly understood in equids. Here, we constructed a single-cell transcriptomic atlas to investigate ovarian changes in Kazakh horses. Using single-cell RNA sequencing (scRNA-seq), we profiled 112,861 cells from follicle-containing and follicle-absent ovaries, identifying nine distinct ovarian cell types and their subtypes, each with distinct gene expression signatures. Functional enrichment analyses revealed cell type-specific engagement in biological pathways, including ECM–receptor interaction, PI3K-Akt signaling, and oxytocin signaling. Gene expression patterns indicated tightly regulated processes of ovarian activation and cell differentiation. Notably, stromal cells exhibited high expression of ROBO2, LOC111770199, and TMTC2, while smooth muscle cells (SMCs) were marked by elevated levels of CCL5, KLRD1, and NKG7. Moreover, cell–cell interaction analyses revealed robust signaling interactions among SMCs, endothelial cells, neurons, and proliferating (cycling) cells. Together, these findings provide a comprehensive single-cell transcriptomic map of normal and abnormal ovarian states during estrus in Kazakh horses, offering novel insights into the cellular mechanisms of follicular development and identifying potential diagnostic biomarkers and therapeutic targets for ovarian quiescence in equids. Full article
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16 pages, 6686 KB  
Article
Integrated Spatial and Single-Cell Transcriptomics Reveals Poor Prognostic Ligand–Receptor Pairs in Glioblastoma
by Makoto Yoshimoto, Kengo Sugihara, Kazuya Tokumura, Shohei Tsuji and Eiichi Hinoi
Cells 2025, 14(19), 1540; https://doi.org/10.3390/cells14191540 - 1 Oct 2025
Viewed by 839
Abstract
Glioblastoma (GBM) is an aggressive and lethal malignant brain tumor. Cell–cell interactions (CCIs) in the tumor microenvironment, mediated by ligand–receptor (LR) pairs, are known to contribute to its poor prognosis. However, the prognostic influence of CCIs on patients with GBM and the spatial [...] Read more.
Glioblastoma (GBM) is an aggressive and lethal malignant brain tumor. Cell–cell interactions (CCIs) in the tumor microenvironment, mediated by ligand–receptor (LR) pairs, are known to contribute to its poor prognosis. However, the prognostic influence of CCIs on patients with GBM and the spatial expression profiles of such LR pairs within tumor tissues remain incompletely understood. This study aimed to identify prognostic LR pairs in GBM and their intratumoral localization via multitranscriptomic analysis. The CCIs among GBM cells as well as between GBM and niche cells were comprehensively evaluated using 40,958 cells in single-cell RNA sequencing datasets. They were found to form intercellular networks in GBM by specific LR pairs, which were mainly implicated in extracellular matrix (ECM)-related biological processes. Survival analysis revealed that 13 LR pairs related to ECM biological processes contributed to poor prognosis (p < 0.05, and 95% confidence intervals > 1). Notably, our spatial transcriptomic analysis using three independent GBM cohorts revealed that the identified poor prognostic LR pairs were localized in specific regions within GBM tissues. Although the clinical importance of these LR pairs requires further investigation, our findings suggest potential therapeutic targets for GBM. Full article
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16 pages, 1246 KB  
Article
Single-Cell Transcriptomic Profiling of Longissimus Dorsi and Biceps Femoris Muscles in Kazakh Horses Reveals Cellular Heterogeneity and Myogenic Regulation
by Jianwen Wang, Zexu Li, Luling Li, Ran Wang, Shikun Ma, Yi Su, Dehaxi Shan and Qiuping Huang
Animals 2025, 15(19), 2778; https://doi.org/10.3390/ani15192778 - 23 Sep 2025
Viewed by 313
Abstract
Kazakh horses are renowned for their endurance and adaptability, with distinct muscle groups such as the longissimus dorsi (LD) and biceps femoris (BF) muscles serving specialized functions. However, the molecular mechanisms underlying the functional specialization of these muscles in Kazakh horses remain poorly [...] Read more.
Kazakh horses are renowned for their endurance and adaptability, with distinct muscle groups such as the longissimus dorsi (LD) and biceps femoris (BF) muscles serving specialized functions. However, the molecular mechanisms underlying the functional specialization of these muscles in Kazakh horses remain poorly understood. This study aims to address this gap by utilizing single-cell RNA sequencing (scRNA-seq) to investigate the transcriptomic differences between these muscle groups, with a focus on understanding their molecular adaptations. Our analysis revealed that the BF muscle, specialized for explosive movements, exhibited upregulation of genes associated with anaerobic metabolism, muscle contraction, and oxidative stress response, reflecting its reliance on glycolysis for sustained energy production. In contrast, the LD muscle, primarily responsible for postural support and endurance, showed a metabolic shift toward lipid utilization and energy production. Differential gene expression analysis also revealed distinct enrichment in biological pathways, with LD cells being enriched in pathways related to muscle contraction and calcium signaling, while BF cells were enriched in energy metabolism pathways. These findings provide valuable insights into the molecular adaptations of Kazakh horses’ muscle tissues, highlighting the functional specialization of LD and BF muscles and offering a foundation for future research on improving muscle performance and breeding programs in equines. Full article
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38 pages, 578 KB  
Review
Next-Generation Sequencing: A Review of Its Transformative Impact on Cancer Diagnosis, Treatment, and Resistance Management
by Alexandru Isaic, Nadica Motofelea, Teodora Hoinoiu, Alexandru Catalin Motofelea, Ioan Cristian Leancu, Emanuela Stan, Simona R. Gheorghe, Alina Gabriela Dutu and Andreea Crintea
Diagnostics 2025, 15(19), 2425; https://doi.org/10.3390/diagnostics15192425 - 23 Sep 2025
Viewed by 988
Abstract
Background/Objectives: Next-Generation Sequencing (NGS) has transformed cancer diagnostics and treatment by enabling comprehensive genomic profiling of tumors. This review aims to summarize the current applications of NGS in oncology, highlighting its role in early detection, precision therapy, and disease monitoring. Methods: [...] Read more.
Background/Objectives: Next-Generation Sequencing (NGS) has transformed cancer diagnostics and treatment by enabling comprehensive genomic profiling of tumors. This review aims to summarize the current applications of NGS in oncology, highlighting its role in early detection, precision therapy, and disease monitoring. Methods: We conducted a comprehensive review of the recent literature, focusing on the application of NGS in cancer care. Results: NGS enables high-resolution genomic profiling, identifying actionable mutations (e.g., EGFR, KRAS, and ALK) and immunotherapy biomarkers (e.g., PD-L1, TMB, and MSI), guiding personalized treatment selection and improving outcomes in advanced malignancies. Liquid biopsy enhances diagnostic accessibility and enables real-time monitoring of minimal residual disease and treatment resistance. Despite these advances, widespread clinical adoption remains constrained by technical limitations (e.g., coverage uniformity and sample quality), economic challenges (high costs and complex reimbursement), and interpretative issues, including the management of variants of uncertain significance (VUSs). Conclusions: NGS is central to precision oncology, enabling molecularly driven cancer care. Integration with artificial intelligence, single-cell sequencing, spatial transcriptomics, multi-omics, and nanotechnology promises to overcome current limitations, advancing personalized treatment strategies. Standardization of workflows, cost reduction, and improved bioinformatics expertise are critical for its full clinical integration. Full article
23 pages, 5765 KB  
Article
Orlistat Confers Neuroprotection in Traumatic Brain Injury by Modulating Microglial Lipid Metabolism
by Chenxuan Yu, Yu Ni, Yuxuan Xiong, Huayu Kang, Zhengqiao Jiang, Yuan Liu, Xincheng Zhang, Yanchao Liu, Kai Zhao, Sheng Wang, Chao Gan and Huaqiu Zhang
Cells 2025, 14(18), 1469; https://doi.org/10.3390/cells14181469 - 19 Sep 2025
Viewed by 478
Abstract
Traumatic brain injury (TBI) represents a major cause of mortality and disability worldwide, particularly affecting young adults and elderly populations. This study investigates the neuroprotective potential of orlistat (ORL), a gastrointestinal lipase inhibitor, in a murine TBI model. Behavioral, histological, and molecular analyses [...] Read more.
Traumatic brain injury (TBI) represents a major cause of mortality and disability worldwide, particularly affecting young adults and elderly populations. This study investigates the neuroprotective potential of orlistat (ORL), a gastrointestinal lipase inhibitor, in a murine TBI model. Behavioral, histological, and molecular analyses demonstrated that ORL significantly attenuated TBI-induced neurological damage. Microglial depletion experiments revealed that ORL’s neuroprotective effects were largely mediated through microglial modulation. In vitro and in vivo studies showed that ORL suppressed microglial activation, phagocytosis, and migration. Single-cell RNA sequencing identified upregulation of lipoprotein lipase (LPL) in a TBI-induced microglial subpopulation. Molecular docking predicted ORL-LPL binding, suggesting direct enzymatic inhibition. Transcriptomic and metabolomic analyses further revealed ORL’s modulation of microglial metabolic pathways and inflammatory responses. Our findings position ORL as a promising repurposed therapeutic for TBI through its novel mechanism of targeting microglial LPL-mediated neuroinflammation. Full article
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17 pages, 7343 KB  
Article
Single-Cell Transcriptome Reveals the Regulatory Role of STAT3 in Diquat-Induced Oxidative Stress in Piglet Hepatocytes
by Yunpeng Li, Jia Li, Hongjin Li, Chu Zhang, Yongqing Zeng, Jin Wang and Wei Chen
Int. J. Mol. Sci. 2025, 26(18), 9161; https://doi.org/10.3390/ijms26189161 - 19 Sep 2025
Viewed by 377
Abstract
Oxidative stress (OS) is known to cause severe liver injury in weaning piglets; however, the cellular and molecular mechanisms underlying this process remain poorly understood. In this study, we employed a diquat (DQ)-induced OS model in weanling piglets and performed single-cell transcriptome sequencing [...] Read more.
Oxidative stress (OS) is known to cause severe liver injury in weaning piglets; however, the cellular and molecular mechanisms underlying this process remain poorly understood. In this study, we employed a diquat (DQ)-induced OS model in weanling piglets and performed single-cell transcriptome sequencing of liver tissue to elucidate the key molecular and cellular events involved in OS-induced hepatic damage. First, piglets were treated with 12 mg/kg DQ and the same amount of saline, and the histopathology, biochemical indicators, and single-cell RNA sequencing (scRNA-seq) of piglets were analyzed. Mouse hepatocytes were used to verify the mechanism of differentially expressed genes, including STAT3 knockdown/overexpression, reactive oxygen species (ROS) detection and apoptosis assay. DQ exposure caused significant oxidative damage in the liver of piglets, which was manifested as decreased superoxide dismutase (SOD) activity (p < 0.05), glutathione (GSH) consumption (p < 0.05) and increased malondialdehyde (MDA) (p < 0.05). Cell type-specific responses were revealed by scRNA-seq, with hepatocytes showing the most pronounced transcriptomic alterations (752 genes up-regulated and 918 genes down-regulated). The expression of STAT3 was up-regulated in hepatocytes (p < 0.05) and down-regulated in B cells. The functional enrichment of macrophages involved FOXO/MAPK signaling and OS pathways. In vitro experiments showed that DQ treatment (IC50 = 125.8 μmol/L) led to an increase in ROS content and apoptosis, STAT3 silencing aggravated ROS and apoptosis (p < 0.05), and STAT3 overexpression alleviated ROS and apoptosis (p < 0.05). STAT3 activation increases HO-1 and Bcl-2, while inhibiting Bax and shifting the Bax/Bcl-2 ratio toward cell survival. It has been shown that DQ induces OS and apoptosis in a cell type-dependent manner, in which STAT3 plays a key regulatory role in antioxidant defense and cell survival. Targeting STAT3 may be a therapeutic strategy for DQ-induced hepatotoxicity. Full article
(This article belongs to the Section Molecular Biology)
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28 pages, 3457 KB  
Review
Alveolar Epithelial Cell Dysfunction in Acute Respiratory Distress Syndrome: Mechanistic Insights and Targeted Interventions
by Jing Wang and Jie Chao
Biomedicines 2025, 13(9), 2299; https://doi.org/10.3390/biomedicines13092299 - 19 Sep 2025
Viewed by 971
Abstract
Acute respiratory distress syndrome (ARDS) is a life-threatening condition with high mortality. A central driver in its pathogenesis is alveolar epithelial cell (AEC) dysfunction, which leads to disruption of the epithelial barrier, impaired fluid clearance, and dysregulated inflammatory responses. This review summarizes the [...] Read more.
Acute respiratory distress syndrome (ARDS) is a life-threatening condition with high mortality. A central driver in its pathogenesis is alveolar epithelial cell (AEC) dysfunction, which leads to disruption of the epithelial barrier, impaired fluid clearance, and dysregulated inflammatory responses. This review summarizes the key mechanisms underlying AEC injury, including programmed cell death (apoptosis, pyroptosis, necroptosis, ferroptosis), oxidative stress, mitochondrial dysfunction, epigenetic reprogramming (DNA methylation, histone modifications), metabolic rewiring (succinate accumulation), and spatiotemporal heterogeneity revealed by single-cell sequencing and spatial transcriptomics. Multicellular crosstalk involving epithelial–immune–endothelial networks and the gut-lung axis further shapes disease progression. Building on these mechanistic foundations, we evaluate emerging AEC-targeted interventions such as pharmacologic agents (antioxidants, anti-inflammatories), biologics (mesenchymal stem cells and engineered exosomes), and gene-based approaches (adeno-associated virus and CRISPR-Cas9 systems delivered via smart nanocarriers). Complementary strategies include microbiome modulation through probiotics, short-chain fatty acids, or fecal microbiota transplantation, and biomarker-guided precision medicine (e.g., sRAGE, exosomal miRNAs) to enable promise individualized regimens. We also discuss translational hurdles, including nanotoxicity, mesenchymal stem cell (MSC) heterogeneity, and gene-editing safety, and highlight future opportunities involving AI-driven multi-omics, lung-on-chip platforms, and epithelium-centered regenerative therapies. By integrating mechanistic insights with innovative therapeutic strategies, this review aims to outline a roadmap toward epithelium-targeted, precision-guided therapies for ARDS. Full article
(This article belongs to the Section Cell Biology and Pathology)
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31 pages, 626 KB  
Review
Single-Cell Transcriptomics in Inherited Retinal Dystrophies: Current Findings and Emerging Perspectives
by Linda Nguyen, Catalina A. Vallejos, Pleasantine Mill and Roly Megaw
Genes 2025, 16(9), 1088; https://doi.org/10.3390/genes16091088 - 16 Sep 2025
Viewed by 710
Abstract
Inherited retinal dystrophies (IRDs) represent a diverse group of disorders caused by mutations in genes essential for retinal function and maintenance. Traditional bulk RNA sequencing techniques provide valuable information for deciphering disease pathogenesis but lack the resolution to capture variation among specific cell [...] Read more.
Inherited retinal dystrophies (IRDs) represent a diverse group of disorders caused by mutations in genes essential for retinal function and maintenance. Traditional bulk RNA sequencing techniques provide valuable information for deciphering disease pathogenesis but lack the resolution to capture variation among specific cell clusters during disease progression. In contrast, single-cell transcriptomics, including single-cell RNA sequencing (scRNA-seq), enables detailed examination of distinct retinal clusters in both healthy and diseased states, uncovering unique gene expression signatures and early molecular changes preceding photoreceptor cell death in IRDs. These insights not only deepen our understanding of the complex pathogenesis of IRDs but also highlight potential targets for novel therapeutic interventions. In this review, we examine the recent literature on the application of single-cell transcriptomics in IRDs to explore how these techniques enhance our understanding of disease mechanisms and contribute to the identification of new therapeutic targets. Full article
(This article belongs to the Special Issue Genetics in Retinal Diseases—2nd Edition)
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14 pages, 2734 KB  
Article
Dual Therapeutic Impact of AXL Inhibitor AB-329: Chemotherapy Sensitization and Immune Microenvironment Reprogramming in TNBC
by Dileep Reddy Rampa, Jon A. Fuson, Huey Liu, Max Pan, Yujia Qin, Youping Deng, Naoto T. Ueno and Jangsoon Lee
Int. J. Mol. Sci. 2025, 26(18), 8896; https://doi.org/10.3390/ijms26188896 - 12 Sep 2025
Viewed by 497
Abstract
AXL, a receptor tyrosine kinase, has emerged as a promising therapeutic target in triple-negative breast cancer (TNBC) due to its critical roles in tumor progression, metastasis, and immune evasion. In this study, we investigated the antitumor efficacy and immunomodulatory potential of AB-329, a [...] Read more.
AXL, a receptor tyrosine kinase, has emerged as a promising therapeutic target in triple-negative breast cancer (TNBC) due to its critical roles in tumor progression, metastasis, and immune evasion. In this study, we investigated the antitumor efficacy and immunomodulatory potential of AB-329, a selective AXL kinase inhibitor, in preclinical models of TNBC. Transcriptome analysis and single-cell RNA sequencing datasets revealed elevated AXL expression in mesenchymal TNBC subtypes and a negative association with immune cell infiltration. While AB-329 demonstrated moderate antiproliferative effects as a monotherapy, its combination with paclitaxel led to substantially enhanced antiproliferative and anti-metastatic effects compared to gemcitabine, DXd, and SN-38. In murine TNBC allograft models, the combination of AB-329 and paclitaxel significantly reduced tumor growth, and AB-329 increased activated natural killer (NK) cell infiltration in humanized mouse models. Analysis of human breast cancer tissue further confirmed that low AXL expression is associated with a higher presence of NK cells in the tumor. These findings suggest that AB-329 not only augments chemotherapy efficacy but also reshapes the tumor immune microenvironment, supporting its further development as a dual-action therapeutic strategy for AXL-positive TNBC. Full article
(This article belongs to the Special Issue Progress in New Agents to Treat Breast Cancer)
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