Frontiers in bioscience (Landmark edition)最新文献

{"title":"Gut Microbial Load As a Hidden Driver of Microbiome Diversity and Function.","authors":"Miroslava Žoldáková, Natália Chomová, Gabriel Žoldák","doi":"10.31083/FBL39516","DOIUrl":"https://doi.org/10.31083/FBL39516","url":null,"abstract":"","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"39516"},"PeriodicalIF":3.1,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Humanized Fruit Flies as a Novel Pre-Clinical Test Model for Membrane Drug Transporters.","authors":"Yiwen Wang, Jing Yang, Elke Schaeffeler, Simon U Jaeger, Matthias Schwab, Anne T Nies, Bernard Moussian","doi":"10.31083/FBL42817","DOIUrl":"https://doi.org/10.31083/FBL42817","url":null,"abstract":"<p><strong>Background: </strong>Membrane transport proteins are critical determinants of systemic and intracellular drug levels, thereby contributing substantially to drug response and/or adverse drug reactions. Therefore, the U.S. Food and Drug Administration and the European Medicines Agency, the regulatory authorities for drug approval in the U.S. and Europe, respectively, recommend pre-clinical testing of selected drug transporters during the drug development process to elucidate clinically relevant drug-drug interactions (DDIs). In the current proof-of-principle study, we describe the generation of fruit flies expressing human membrane drug transporters in their salivary glands to enable DDI studies in a time-saving manner and at low costs.</p><p><strong>Methods: </strong>Using the Gal4/upstream activation sequence (UAS) expression system, we established fruit flies expressing human organic cation transporters (hOCTs) 1 and 2 and genetic variants thereof. Both transporters are key drug uptake transporters in humans and are recommended for pre-clinical DDI studies. After injecting fluorescent hOCT substrates, their accumulation in salivary gland cells was observed by confocal laser scanning microscopy.</p><p><strong>Results: </strong>We demonstrate the feasibility of expressing hOCT1 and hOCT2 in the salivary glands of fruit fly embryos and subsequent alteration by clinically relevant genetic variants, corroborating results from mammalian cell experiments. Moreover, we show an OCT-dependent accumulation of the prototypic fluorescent OCT substrates ethidium (Et⁺) and 4-Di-1-ASP (4-(4-(dimethylamino)styryl)-N-methylpyridinium, ASP⁺) in the salivary gland cells and subsequent inhibition by clinically-used OCT drug inhibitors.</p><p><strong>Conclusions: </strong>Based on the handling procedure and the lack of need for Animal Protection Act approval, we propose that the humanized <i>Drosophila melanogaster</i> fruit fly model opens a new avenue for pre-clinical functional transporter studies.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"42817"},"PeriodicalIF":3.1,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GD2-Specific CAR T Cells Demonstrate Potent and Targeted Anti-Tumor Efficacy Against Melanoma <i>In Vitro</i> and <i>In Vivo</i>.","authors":"Julia Philippova, Julia Shevchenko, Alaa Alsalloum, Marina Fisher, Saleh Alrhmoun, Roman Perik-Zavodskii, Olga Perik-Zavodskaia, Julia Lopatnikova, Vasily Kurilin, Marina Volynets, Evgenii Zavjalov, Olga Solovieva, Hiroshi Shiku, Sergey Sennikov","doi":"10.31083/FBL41221","DOIUrl":"https://doi.org/10.31083/FBL41221","url":null,"abstract":"<p><strong>Background: </strong>Disialoganglioside (GD2) is a tumor-associated antigen that is highly expressed in various neuroectodermal cancers, including melanoma. While chimeric antigen receptor (CAR) T-cell immunotherapy has demonstrated remarkable success in treating hematologic neoplasms, the identification of suitable targets remains a major obstacle in translating this approach to solid tumors.</p><p><strong>Methods: </strong>Peripheral blood T lymphocytes from six healthy donors were used to generate GD2-specific CAR T cells via retroviral transduction. The resulting GD2.CAR T cells were characterized by NanoString transcriptome profiling, flow cytometry with hierarchical stochastic neighbor embedding (HSNE) dimensionality reduction, and <i>in vitro</i> cytotoxicity assays against GD2⁺ and GD2^- melanoma cell lines. <i>In vivo</i> experiments were also performed using GD2⁺ xenograft models and a single intratumoral dose of 8 × 10⁶ GD2.CAR T cells.</p><p><strong>Result: </strong>The GD2.CAR T cell population exhibited a predominantly naive phenotype (CD8⁺CD40L⁺CD69^‒CD107a⁺4-1BB⁺FasL⁺) and effective anti-tumor mechanisms involving the granzyme A/B axis, the Fas/FasL axis, and cytokine release. Transcriptome analysis revealed transduction-related effects on proliferation and a shift towards an effector phenotype during early co-culture with tumor cells, accompanied by upregulation of interferon-gamma (IFN-γ) and cytokine signaling genes. GD2.CAR T cells demonstrated robust cytotoxicity against GD2⁺ melanoma cells <i>in vitro</i>, while significant <i>in vivo</i> tumor control was observed in xenograft models.</p><p><strong>Conclusion: </strong>GD2.CAR T cells demonstrate potent anti-tumor activity against melanoma <i>in vitro</i> and <i>in vivo</i>, highlighting their therapeutic potential and warranting further clinical investigation.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"41221"},"PeriodicalIF":3.1,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Analysis of BMI and Gene Expression Reveals Molecular Interactions Underlying Cancer Progression.","authors":"Jie-Huei Wang, Hui-Chen Lu, Zih-Han Wu, Tzu-Chi Chang","doi":"10.31083/FBL43294","DOIUrl":"https://doi.org/10.31083/FBL43294","url":null,"abstract":"<p><strong>Background: </strong>Obesity is a chronic condition linked to health issues such as diabetes, heart disease, and increased cancer risk. High body mass index (BMI) is associated with cancers such as breast and colorectal cancer due to hormone imbalances and inflammation from excess fat, whereas a low BMI can raise cancer risk by weakening the immune system. Maintaining a normal BMI improves cancer treatment outcomes, but in some cases, higher BMI might offer protective effects-a phenomenon known as the \"obesity paradox\". This study explores how BMI affects gene expression in cancer, using data from The Cancer Genome Atlas (TCGA), aiming to uncover links between BMI and cancer progression while identifying potential treatment targets.</p><p><strong>Methods: </strong>To analyze the data, a two-stage method using overlapping group screening (OGS) was applied. First, gene groups were identified with the \"grpregOverlap\" R package. Then, their interactions were tested using the sequence kernel association test. Significant gene-gene interactions were selected based on statistical measures. In the second stage, predictive models were built using regularized regression techniques such as ridge regression, lasso, and adaptive lasso, with generalized ridge regression used to improve accuracy and stability in handling high-dimensional data.</p><p><strong>Results: </strong>The proposed OGS-based method was tested on simulated and real-world datasets. Results showed that combining OGS with generalized ridge regression and adaptive lasso (OGS_G.ridge_ALasso) gave the best prediction performance, with lower error rates and greater stability compared to other models like support vector regression, k-nearest neighbors, and random forests. In practical applications, gene expression and BMI data from TCGA patients (including bladder, cervical, esophageal and liver cancers) were integrated to identify key genes and interactions related to BMI.</p><p><strong>Conclusions: </strong>Through evaluations on both simulated synthetic datasets and real-world datasets, we demonstrated the effectiveness of the proposed method in terms of predictive accuracy. Additionally, we identified BMI-associated genes and gene-gene interaction biomarkers across different cancer types and presented the corresponding network structures. Based on the key genes and gene interactions identified, we further explored how BMI influences cancer development and prognosis, providing deeper insights into the biological mechanisms underlying these associations.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"43294"},"PeriodicalIF":3.1,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sparc Suppresses Microglial Neuroinflammation and Promotes Axonal Regeneration by Interacting With Uba52.","authors":"Hangyu Ji, Kun Wang, Yili Hu, Yefu Xu, Jiangkai Yu, Chengming Li","doi":"10.31083/FBL42005","DOIUrl":"https://doi.org/10.31083/FBL42005","url":null,"abstract":"<p><strong>Background: </strong>After spinal cord injury (SCI), pro-inflammatory microglia accumulate and impede axonal regeneration. We explored whether secreted protein acidic and rich in cysteine (Sparc) restrains microglial inflammation and fosters neurite outgrowth.</p><p><strong>Methods: </strong>Mouse microglial BV2 cells were polarized to a pro-inflammatory phenotype with lipopolysaccharides (LPSs). <i>Sparc</i> mRNA and protein were quantified by reverse transcription quantitative PCR (RT-qPCR). <i>Sparc</i> was overexpressed via plasmid transfection, then inflammatory cytokines, mitochondrial membrane potential (Δψm), reactive oxygen species (ROS), and oxidative-phosphorylation proteins, including voltage-dependent anion channel 1 (VDAC1), cytochrome c oxidase subunit 1 (COX1), and ATP synthase α subunit (ATP5A), were assayed by Western blot, enzyme-linked immunosorbent assay (ELISA), and flow cytometry. Immunoprecipitation plus mass spectrometry, co-immunoprecipitation, and immunofluorescence confirmed the interaction between Sparc and ubiquitin A-52 residue ribosomal protein fusion product 1 (Uba52). Effects of <i>Sparc</i> overexpression alone or combined with <i>Uba52</i> small interfering RNA (si-<i>Uba52</i>) were compared in LPS-induced BV2 cells. Finally, BV2 cells and a mouse hippocampal neuron (HT-22) were co-cultured in the Transwell chamber, and the changes in proliferation, apoptosis, and III-tubulin content of the latter were detected.</p><p><strong>Results: </strong>In LPS-induced BV2 cells, the tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and ROS levels were elevated, while the IL-10 and transforming growth factor-β (TGF-β) levels, Δψm, and the proteins levels of the VDAC1, COX1, ATP5A, and Sparc decreased. <i>Sparc</i> overexpression reversed these changes. Mechanistically, Sparc bound Uba52 and upregulated its expression; <i>Uba52</i> knockdown abolished the anti-inflammatory and mitochondrial-protective effects of Sparc. In co-culture, <i>Sparc</i> overexpression rescued HT-22 neurons apoptosis and enhanced axonal growth, but the effects were also reversed by <i>Uba52</i> knockdown.</p><p><strong>Conclusions: </strong>Sparc may maintain mitochondrial homeostasis by interacting with Uba52 to inhibit LPS-induced BV2 inflammatory response, thereby promoting neuronal axonal regeneration. This suggests that Sparc may play a potential role in SCI repair.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"42005"},"PeriodicalIF":3.1,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Requirement of Lysosomal Two-Pore Channels for Normal Fertilization and Artificial Oocyte Activation in Mice.","authors":"Tadashi Yamazaki, Md Wasim Bari, Satoshi Kishigami","doi":"10.31083/FBL42710","DOIUrl":"https://doi.org/10.31083/FBL42710","url":null,"abstract":"<p><strong>Background: </strong>Lysosomes serve not only in the degradation of cellular components but also as calcium (Ca²⁺) stores. In this study, we investigated the effects of trans-Ned19, an inhibitor of lysosomal calcium channels known to block two-pore channels (TPCs), on fertilization and oocyte activation in mice.</p><p><strong>Methods: </strong>Pronuclear formation was assessed via Hoechst 33342 staining, cortical granule release was evaluated using <i>Lens culinaris</i> agglutinin-fluorescein isothiocyanate (LCA-FITC) staining, intracellular Ca²⁺ levels were monitored with Cal-520 AM, and sperm motility was analyzed using a sperm motility analysis system (SMAS).</p><p><strong>Results: </strong>In strontium (Sr²⁺)-induced oocyte activation, trans-Ned19 significantly reduced pronuclear formation at 8 h post-activation. Cortical granule release and Ca²⁺ oscillations were also markedly suppressed. In contrast, during <i>in vitro</i> fertilization (IVF), trans-Ned19 treatment significantly decreased the fertilization rate; however, pronuclear formation and cortical granule release remained comparable to controls in fertilized embryos. Notably, when IVF was performed using zona pellucida-free oocytes, the fertilization rate in the trans-Ned19 group was similar to that of the controls. However, a significant increase in polyspermy was observed. Furthermore, trans-Ned19 significantly impaired sperm motility parameters, including straight-line velocity, curvilinear velocity, and average path velocity.</p><p><strong>Conclusions: </strong>These findings suggest that lysosomal TPCs are essential for both normal fertilization and artificial oocyte activation in mice.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"42710"},"PeriodicalIF":3.1,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antioxidant Cardioprotection in Acute Myocardial Infarction: From Mechanisms to Therapeutic Strategies.","authors":"Eduardo Villa, Luciano Saso, Silvia Chichiarelli, Catalina Rojas-Solé, Víctor Pinilla-González, Juan Carlos Prieto, Abraham I J Gajardo, Ruben Aguayo, Ramón Rodrigo","doi":"10.31083/FBL27678","DOIUrl":"https://doi.org/10.31083/FBL27678","url":null,"abstract":"<p><p>Acute myocardial infarction (AMI) is one of the main causes of mortality worldwide. Currently, the most effective treatment is percutaneous coronary angioplasty (PCA). However, paradoxically, the restoration of blood flow induces myocardial reperfusion injury (MRI), contributing up to 50% of the final infarct size. Oxidative stress, characterized by a burst of reactive oxygen species (ROS) following reperfusion, plays a fundamental role in its pathophysiology, causing inflammation, endothelial dysfunction, and cell death mainly through autophagy, apoptosis, ferroptosis, necroptosis, and pyroptosis. To mitigate these injury mechanisms, numerous antioxidant strategies have been evaluated using both <i>in vitro</i> and <i>in vivo</i> models with promising results, but limited benefit when tested in humans. Several antioxidants have biological properties that counteract ROS-induced damage by acting as ROS scavengers, metal chelators, and antioxidant enzyme enhancers. In this review, we focus on the mechanisms by which oxidative stress induces cell death after AMI and highlight the most promising therapeutic antioxidant agents that could provide comprehensive protection against MRI. A multitarget cardioprotective strategy, combining interventions with strong preclinical evidence, could provide a more effective approach for reducing MRI. Our study aims to bridge the gap between basic and clinical research and explore the potential clinical applications of antioxidants.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"27678"},"PeriodicalIF":3.1,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knockdown of ITGA2 Promotes Pyroptosis in Thyroid Cancer by Regulating the DNA Damage Response.","authors":"Liang Yan, Dongming Hua, Rong Ying, Xiaoshuang Liu, Jun Jiang, Zhaolong Liu, Yu Feng","doi":"10.31083/FBL27946","DOIUrl":"https://doi.org/10.31083/FBL27946","url":null,"abstract":"<p><strong>Background: </strong>The most common endocrine cancer, thyroid carcinoma (TC), has a dismal prognosis when it reaches an advanced stage. Integrin α-2 (<i>ITGA2</i>) has been implicated in cancer progression, influencing both DNA damage and repair mechanisms. However, it is unknown how ITGA2 influences these processes in TC.</p><p><strong>Methods: </strong><i>ITGA2</i> was identified as a key prognostic gene for TC from the Cancer Genome Atlas-thyroid carcinoma (THCA), GSE3678, GSE29265, and GSE33630 datasets. Functional assays were used to evaluate the impact of <i>ITGA2</i> knockdown on cell viability, migration, apoptosis, invasion, pyroptosis (N-terminal fragment of GSDME, GSDME-N), and cytotoxicity (Lactate dehydrogenase, LDH). DNA damage markers (phosphorylated histone H2AX on serine 139 (γ-H2AX), phosphorylated ataxia telangiectasia mutated (p-ATM), phosphorylated checkpoint kinase 2 (p-CHK2)) and the level of Reactive Oxygen Species (ROS) were used to assess oxidative stress. The impact of <i>ITGA2</i> inhibition on Wnt/β-catenin signaling was evaluated, and a mouse xenograft model assessed tumor growth <i>in vivo</i>.</p><p><strong>Results: </strong><i>ITGA2</i> was significantly overexpressed in TC. Knockdown of <i>ITGA2</i> significantly reduced cell viability, migration, and invasion, while promoting pyroptosis by upregulating cleaved-poly(ADP-ribose) polymerase (PARP) and GSDME-N. <i>ITGA2</i> silencing also increased LDH activity, enhanced the expression of DNA damage markers (p-ATM, γ-H2AX, p-CHK2), and increased ROS levels. Furthermore, suppression of <i>ITGA2</i> activity attenuated the Wnt/β-catenin pathway by reducing the levels of MYC proto-oncogene, bHLH transcription factor (C-myc), CD44 molecule (CD44), slug, snail, β-catenin, and wingless-type MMTV integration site family, member 1 (Wnt-1). <i>ITGA2</i> silencing significantly inhibited tumor growth in a mouse model.</p><p><strong>Conclusion: </strong><i>ITGA2</i> promotes TC progression by regulating the DNA damage response and inhibiting pyroptosis. Knockdown of <i>ITGA2</i> increases oxidative stress, exacerbates DNA damage, and inhibits the Wnt/β-catenin pathway, indicating it may have potential as a treatment target in TC.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"27946"},"PeriodicalIF":3.1,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Transplantation Therapy: A Novel Approach in the Era of Organelle-Centered Regenerative Medicine.","authors":"Ha Rim Shin, Gaheon Lee, Kyung Hwa Kim","doi":"10.31083/FBL37006","DOIUrl":"https://doi.org/10.31083/FBL37006","url":null,"abstract":"<p><p>Mitochondria play crucial roles in maintaining health and influencing disease progression by acting as central regulators of cellular homeostasis and energy production. Dysfunctions in mitochondrial activity are increasingly recognized as key contributors to various pathologies, ultimately impacting healthspan and disease outcomes. However, traditional treatments often do not restore damaged mitochondria to a healthy state. Mitochondrial transplantation, a cellular organelle-based therapy in which mitochondria are introduced into a recipient, has emerged as a novel concept in next-generation therapeutics that overcomes the limitations of current cell-based treatments. This review highlights the unique properties of mitochondria as therapeutic agents, including their ability to restore cellular functions and treat a wide range of diseases. In this review, we focus on the unique role of mitochondria in the regulation of stem cell functions, including stem cell fate, self-renewal, and differentiation. Various perspectives have been explored to better understand mitochondrial transplantation therapy, which harnesses the capacity of mitochondria as living drugs in regenerative medicine, as an innovative strategy to bridge the gap between cell therapy and organelle-based treatments and overcome current clinical barriers.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"37006"},"PeriodicalIF":3.1,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reviewing the Developing Significance of the Serine Protease PRSS23.","authors":"Hans-Juergen Schulten","doi":"10.31083/FBL27294","DOIUrl":"https://doi.org/10.31083/FBL27294","url":null,"abstract":"<p><p>The serine protease 23 (PRSS23) is a highly conserved member of trypsin-like serine proteases, which are associated with numerous essential processes, including digestion, blood coagulation, fibrinolysis, development, fertilization, apoptosis, and immunity. Original reports on PRSS23 unfolded not earlier than 2006 when a molecular biology study characterized and described PRSS23 as an ovarian protease. Then, in 2012, another important study was published linking PRSS23 with proliferation of breast cancer cells by an estrogen receptor 1 (ESR1)-dependent transcriptional activation of the serine protease. Thereafter, a developmental study in zebrafish reported the implication of PRSS23 in endothelial-to-mesenchymal transition (EndMT) during cardiac valve formation. Although these early studies on PRSS23 have revealed its involvement in some critical or fundamental processes, only in recent years an increasing number of studies have evolved describing the expression and functions of PRSS23 in various normal physiological conditions, diseases, and experimental configurations. Besides breast cancer, PRSS23 has been shown to be involved in different types of malignancies, e.g., in gastric cancer, where drug screening found that the protease inhibitor tipranavir impedes cancer-promoting PRSS23 expression. New innovative techniques such as single cell RNA-sequencing (scRNA-seq) and bioinformatics studies accelerated the discovery of gene expression changes in smaller cell populations, which, e.g., led to the identification of marked <i>PRSS23</i> expression in a myofibroblast-like subpopulation in localized scleroderma. This review compiles major and significant research results that have contributed to our current knowledge of PRSS23 and briefly discusses where prospective studies could add to our understanding of this versatile serine protease.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"27294"},"PeriodicalIF":3.1,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}