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41 pages, 1612 KiB  
Review
Navigating the Landscape of Liquid Biopsy in Colorectal Cancer: Current Insights and Future Directions
by Pina Ziranu, Andrea Pretta, Giorgio Saba, Dario Spanu, Clelia Donisi, Paolo Albino Ferrari, Flaviana Cau, Alessandra Pia D’Agata, Monica Piras, Stefano Mariani, Marco Puzzoni, Valeria Pusceddu, Ferdinando Coghe, Gavino Faa and Mario Scartozzi
Int. J. Mol. Sci. 2025, 26(15), 7619; https://doi.org/10.3390/ijms26157619 (registering DOI) - 6 Aug 2025
Abstract
Liquid biopsy has emerged as a valuable tool for the detection and monitoring of colorectal cancer (CRC), providing minimally invasive insights into tumor biology through circulating biomarkers such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), [...] Read more.
Liquid biopsy has emerged as a valuable tool for the detection and monitoring of colorectal cancer (CRC), providing minimally invasive insights into tumor biology through circulating biomarkers such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Additional biomarkers, including tumor-educated platelets (TEPs) and exosomal RNAs, offer further potential for early detection and prognostic role, although ongoing clinical validation is still needed. This review summarizes the current evidence on the diagnostic, prognostic, and predictive capabilities of liquid biopsy in both metastatic and non-metastatic CRC. In the non-metastatic setting, liquid biopsy is gaining traction in early detection through screening and in identifying minimal residual disease (MRD), potentially guiding adjuvant treatment and reducing overtreatment. In contrast, liquid biopsy is more established in metastatic CRC for monitoring treatment responses, clonal evolution, and mechanisms of resistance. The integration of ctDNA-guided treatment algorithms into clinical practice could optimize therapeutic strategies and minimize unnecessary interventions. Despite promising advances, challenges remain in assay standardization, early-stage sensitivity, and the integration of multi-omic data for comprehensive tumor profiling. Future efforts should focus on enhancing the sensitivity of liquid biopsy platforms, validating emerging biomarkers, and expanding multi-omic approaches to support more targeted and personalized treatment strategies across CRC stages. Full article
(This article belongs to the Special Issue Cancer Biology and Epigenetic Modifications)
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19 pages, 5639 KiB  
Article
Nesting and Hibernation Host Preference of Bamboo Carpenter Bee, Xylocopa (Biluna) tranquebarorum tranquebarorum, and Arthropods Co-Habiting and Re-Using the Bee Nest
by Natsumi Kanzaki, Keito Kobayashi, Keiko Hamaguchi and Yuta Fujimori
Insects 2025, 16(8), 807; https://doi.org/10.3390/insects16080807 - 4 Aug 2025
Viewed by 287
Abstract
The bamboo carpenter bee, Xylocopa (Biluna) tranquebarorum tranquebarorum, is native to continental China and Taiwan, and the species invaded Japan around 2006. The bee utilizes bamboo culm for its nesting and hibernation, thereby causing structural damage to bamboo fencing and [...] Read more.
The bamboo carpenter bee, Xylocopa (Biluna) tranquebarorum tranquebarorum, is native to continental China and Taiwan, and the species invaded Japan around 2006. The bee utilizes bamboo culm for its nesting and hibernation, thereby causing structural damage to bamboo fencing and sting injuries to humans. Serious economic and ecological impacts were not expected in the early stage of its invasion. However, its distribution is rapidly expanding in Japan, and thus, its potential impacts need to be evaluated. Since the basic biology of the bee has not been examined in detail, even in its natural range, we examined the basic biology of X. t. tranquebarorum in its invasive range by evaluating its nesting preference and hibernation in several bamboo species collections in Kyoto, Japan. The field survey revealed that the bee prefers dead bamboo internodes with approximately16–28 mm of external diameter, which is well-congruent with previous studies, and does not have strict preference concerning the bamboo species, though the bee prefers Bambusa multiplex and Phyllostachys spp. in its native range. The hibernating bees in the culm sometimes share their nests with other invertebrates, including Anterhynchium gibbifrons, Dinoderus japonicus, Crematogaster matsumurai, unidentified spiders, shield bugs, and lepidopteran larvae. Within these co-habitants, the former two possibly negatively affect nesting and hibernation of the bees. Full article
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23 pages, 5432 KiB  
Article
Unveiling the Bioactive Potential of the Invasive Jellyfish Phyllorhiza punctata Through Integrative Transcriptomic and Proteomic Analyses
by Tomás Rodrigues, Ricardo Alexandre Barroso, Alexandre Campos, Daniela Almeida, Francisco A. Guardiola, Maria V. Turkina and Agostinho Antunes
Biomolecules 2025, 15(8), 1121; https://doi.org/10.3390/biom15081121 - 4 Aug 2025
Viewed by 224
Abstract
The white-spotted jellyfish, Phyllorhiza punctata, is an invasive species with significant ecological and economic relevance spreading across various regions. While its ecological impact is well-documented, its molecular and biochemical characteristics remain poorly understood. In this study, we integrate proteomic data generated by [...] Read more.
The white-spotted jellyfish, Phyllorhiza punctata, is an invasive species with significant ecological and economic relevance spreading across various regions. While its ecological impact is well-documented, its molecular and biochemical characteristics remain poorly understood. In this study, we integrate proteomic data generated by LC-MS/MS with publicly available transcriptomic information to characterize P. punctata, analyzing differential protein expression across three distinct tissues: oral arms, mantle, and gonads. A total of 2764 proteins and 25,045 peptides were identified, including several venom components such as jellyfish toxins (JFTs) and phospholipase A2 (PLA2), which were further investigated and compared to toxins from other species. Enrichment analyses revealed clear tissue-specific functions. Additionally, deep learning and machine learning tools identified 274 promising AMP candidates, including the α-helical, β-sheet, and αβ-motif peptides. This dataset provides new insights into the protein composition of P. punctata and highlights strong AMP candidates for further characterization, underscoring the biotechnological potential of underexplored cnidarian species. Full article
(This article belongs to the Special Issue State of the Art and Perspectives in Antimicrobial Peptides)
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29 pages, 1477 KiB  
Review
Bioinformation and Monitoring Technology for Environmental DNA Analysis: A Review
by Hyo Jik Yoon, Joo Hyeong Seo, Seung Hoon Shin, Mohamed A. A. Abdelhamid and Seung Pil Pack
Biosensors 2025, 15(8), 494; https://doi.org/10.3390/bios15080494 - 1 Aug 2025
Viewed by 326
Abstract
Environmental DNA (eDNA) analysis has emerged as a transformative tool in environmental monitoring, enabling non-invasive detection of species and microbial communities across diverse ecosystems. This study systematically reviews the role of bioinformation technology in eDNA analysis, focusing on methodologies and applications across air, [...] Read more.
Environmental DNA (eDNA) analysis has emerged as a transformative tool in environmental monitoring, enabling non-invasive detection of species and microbial communities across diverse ecosystems. This study systematically reviews the role of bioinformation technology in eDNA analysis, focusing on methodologies and applications across air, soil, groundwater, sediment, and aquatic environments. Advances in molecular biology, high-throughput sequencing, bioinformatics tools, and field-deployable detection systems have significantly improved eDNA detection sensitivity, allowing for early identification of invasive species, monitoring ecosystem health, and tracking pollutant degradation processes. Airborne eDNA monitoring has demonstrated potential for assessing microbial shifts due to air pollution and tracking pathogen transmission. In terrestrial environments, eDNA facilitates soil and groundwater pollution assessments and enhances understanding of biodegradation processes. In aquatic ecosystems, eDNA serves as a powerful tool for biodiversity assessment, invasive species monitoring, and wastewater-based epidemiology. Despite its growing applicability, challenges remain, including DNA degradation, contamination risks, and standardization of sampling protocols. Future research should focus on integrating eDNA data with remote sensing, machine learning, and ecological modeling to enhance predictive environmental monitoring frameworks. As technological advancements continue, eDNA-based approaches are poised to revolutionize environmental assessment, conservation strategies, and public health surveillance. Full article
(This article belongs to the Section Environmental Biosensors and Biosensing)
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27 pages, 5245 KiB  
Article
The Good, the Bad, or Both? Unveiling the Molecular Functions of LINC01133 in Tumors
by Leandro Teodoro Júnior and Mari Cleide Sogayar
Non-Coding RNA 2025, 11(4), 58; https://doi.org/10.3390/ncrna11040058 - 30 Jul 2025
Viewed by 296
Abstract
Background/Objectives: Increasing evidence suggests that lncRNAs are core regulators in the field of tumor progression, with context-specific functions in oncogenic tumorigenesis. LINC01133, a lncRNA that has been identified as both an oncogene and a tumor suppressor, remains largely unexplored in terms of its [...] Read more.
Background/Objectives: Increasing evidence suggests that lncRNAs are core regulators in the field of tumor progression, with context-specific functions in oncogenic tumorigenesis. LINC01133, a lncRNA that has been identified as both an oncogene and a tumor suppressor, remains largely unexplored in terms of its molecular mechanisms. The purpose of this study was to conduct an in silico analysis, incorporating literature research on various cancer types, to investigate the structural and functional duality of LINC01133. This analysis aimed to identify pathways influenced by LINC01133 and evaluate its mechanism of action as a potential therapeutic target and diagnostic biomarker. Methods: In silico analyses and a narrative review of the literature were performed to predict conserved structural elements, functional internal loops, and overall conservation of the LINC01133 sequence among different vertebrate organisms, summarizing the empirical evidence regarding its roles as a tumor suppressor and tumor-promoting roles in various types of tumors. Results: LINC01133 harbors the evolutionarily conserved structural regions that might allow for binding to relevant driver signaling pathways, substantiating its specific functionality. Its action extends beyond classical tumor mechanisms, affecting proliferation, migration, invasion, and epigenetic pathways in various types of tumors, as indicated by the in silico results and narrative review of the literature we present here. Clinical outcome associations pointed to its potential as a biomarker. Conclusions: The dual character of LINC01133 in tumor biology further demonstrates its prospective therapeutic value, but complete elucidation of its mechanisms of action requires further investigation. This study establishes LINC01133 as a multifaceted lncRNA, supporting context-specific strategies in targeting its pathways, and calls for expanded research to harness its full potential in oncology. Full article
(This article belongs to the Special Issue Non-coding RNA as Biomarker in Cancer)
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21 pages, 2831 KiB  
Review
IL-20 Subfamily Biological Effects: Mechanistic Insights and Therapeutic Perspectives in Cancer
by Valentina Maggisano, Maria D’Amico, Saveria Aquila, Francesca Giordano, Anna Martina Battaglia, Adele Chimento, Flavia Biamonte, Diego Russo, Vincenzo Pezzi, Stefania Bulotta and Francesca De Amicis
Int. J. Mol. Sci. 2025, 26(15), 7320; https://doi.org/10.3390/ijms26157320 - 29 Jul 2025
Viewed by 175
Abstract
The interleukin-20 (IL-20) cytokine subfamily, a subset of the IL-10 superfamily, includes IL-19, IL-20, IL-22, IL-24, and IL-26. Recently, their involvement in cancer biology has gained attention, particularly due to their impact on the tumor microenvironment (TME). Notably, IL-20 subfamily cytokines can exert [...] Read more.
The interleukin-20 (IL-20) cytokine subfamily, a subset of the IL-10 superfamily, includes IL-19, IL-20, IL-22, IL-24, and IL-26. Recently, their involvement in cancer biology has gained attention, particularly due to their impact on the tumor microenvironment (TME). Notably, IL-20 subfamily cytokines can exert both pro-tumorigenic and anti-tumorigenic effects, depending on the context. For example, IL-22 promotes tumor growth by enhancing cancer cell proliferation and protecting against apoptosis, whereas IL-24 demonstrates anti-tumor activity by inducing cancer cell death and inhibiting metastasis. Additionally, these cytokines influence macrophage polarization—an essential factor in the immune landscape of tumors—thereby modulating the inflammatory environment and immune evasion strategies. Understanding the dual role of IL-20 subfamily cytokines within the TME and their interactions with cancer cell hallmarks presents a promising avenue for therapeutic development. Interleukin-20 receptor antagonists are being researched for their role in cancer therapy, since they potentially inhibit tumor growth and progression. This review explores the relationship between IL-20 cytokines and key cancer-related processes, including growth and proliferative advantages, angiogenesis, invasion, metastasis, and TME support. Further research is necessary to unravel the specific mechanisms underlying their contributions to tumor progression and to determine their potential for targeted therapeutic strategies. Full article
(This article belongs to the Special Issue Advanced Research on Immune Cells and Cytokines (2nd Edition))
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32 pages, 1740 KiB  
Review
Cancer-Associated Fibroblasts: Immunosuppressive Crosstalk with Tumor-Infiltrating Immune Cells and Implications for Therapeutic Resistance
by Jogendra Singh Pawar, Md. Abdus Salam, Md. Shalman Uddin Dipto, Md. Yusuf Al-Amin, Moushumi Tabassoom Salam, Sagnik Sengupta, Smita Kumari, Lohitha Gujjari and Ganesh Yadagiri
Cancers 2025, 17(15), 2484; https://doi.org/10.3390/cancers17152484 - 28 Jul 2025
Viewed by 521
Abstract
Cancer is no longer considered as an isolated event. Rather, it occurs because of a complex biological drive orchestrating different cell types, growth factors, cytokines, and signaling pathways within the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are the most populous stromal cells within [...] Read more.
Cancer is no longer considered as an isolated event. Rather, it occurs because of a complex biological drive orchestrating different cell types, growth factors, cytokines, and signaling pathways within the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are the most populous stromal cells within the complex ecosystem of TME, with significant heterogeneity and plasticity in origin and functional phenotypes. Very enigmatic cells, CAFs determine the progress and outcomes of tumors through extensive reciprocal signaling with different tumors infiltrating immune cells in the TME. In their biological drive, CAFs release numerous chemical mediators and utilize various signaling pathways to recruit and modulate tumor-infiltrating immune cells. The CAF-induced secretome and exosomes render immune cells ineffective for their antitumor activities. Moreover, by upregulating immune inhibitory checkpoints, CAFs create an immunosuppressive TME that impedes the susceptibility of tumor cells to tumor-infiltrating lymphocytes (TILs). Further, by depositing and remodeling extracellular matrix (ECM), CAFs reshape the TME, which enhances tumor growth, invasion, metastasis, and chemoresistance. Understanding of CAF biology and its crosstalk with tumor-infiltrating immune cells is crucial not only to gain insight in tumorigenesis but to optimize the potential of novel targeted immunotherapies for cancers. The complex relationships between CAFs and tumor-infiltrating immune cells remain unclear and need further study. Herein, in this narrative review we have focused on updates of CAF biology and its interactions with tumor-infiltrating immune cells in generating immunosuppressive TME and resistance to cell death. Full article
(This article belongs to the Section Tumor Microenvironment)
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29 pages, 2815 KiB  
Review
Plasmonic Nanostructures for Exosome Biosensing: Enabling High-Sensitivity Diagnostics
by Seungah Lee, Nayra A. M. Moussa and Seong Ho Kang
Nanomaterials 2025, 15(15), 1153; https://doi.org/10.3390/nano15151153 - 25 Jul 2025
Viewed by 361
Abstract
Exosomes are nanoscale extracellular vesicles (EVs) that carry biomolecular signatures reflective of their parent cells, making them powerful tools for non-invasive diagnostics and therapeutic monitoring. Despite their potential, clinical application is hindered by challenges such as low abundance, heterogeneity, and the complexity of [...] Read more.
Exosomes are nanoscale extracellular vesicles (EVs) that carry biomolecular signatures reflective of their parent cells, making them powerful tools for non-invasive diagnostics and therapeutic monitoring. Despite their potential, clinical application is hindered by challenges such as low abundance, heterogeneity, and the complexity of biological samples. To address these limitations, plasmonic biosensing technologies—particularly propagating surface plasmon resonance (PSPR), localized surface plasmon resonance (LSPR), and surface-enhanced Raman scattering (SERS)—have been developed to enable label-free, highly sensitive, and multiplexed detection at the single-vesicle level. This review outlines recent advancements in nanoplasmonic platforms for exosome detection and profiling, emphasizing innovations in nanostructure engineering, microfluidic integration, and signal enhancement. Representative applications in oncology, neurology, and immunology are discussed, along with the increasingly critical role of artificial intelligence (AI) in spectral interpretation and diagnostic classification. Key technical and translational challenges—such as assay standardization, substrate reproducibility, and clinical validation—are also addressed. Overall, this review highlights the synergy between exosome biology and plasmonic nanotechnology, offering a path toward real-time, precision diagnostics via sub-femtomolar detection of exosomal miRNAs through next-generation biosensing strategies. Full article
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35 pages, 6030 KiB  
Review
Common Ragweed—Ambrosia artemisiifolia L.: A Review with Special Regards to the Latest Results in Protection Methods, Herbicide Resistance, New Tools and Methods
by Bence Knolmajer, Ildikó Jócsák, János Taller, Sándor Keszthelyi and Gabriella Kazinczi
Agronomy 2025, 15(8), 1765; https://doi.org/10.3390/agronomy15081765 - 23 Jul 2025
Viewed by 435
Abstract
Common ragweed (Ambrosia artemisiifolia L.) has been identified as one of the most harmful invasive weed species in Europe due to its allergenic pollen and competitive growth in diverse habitats. In the first part of this review [Common Ragweed—Ambrosia artemisiifolia L.: [...] Read more.
Common ragweed (Ambrosia artemisiifolia L.) has been identified as one of the most harmful invasive weed species in Europe due to its allergenic pollen and competitive growth in diverse habitats. In the first part of this review [Common Ragweed—Ambrosia artemisiifolia L.: A Review with Special Regards to the Latest Results in Biology and Ecology], its biological characteristics and ecological behavior were described in detail. In the current paper, control strategies are summarized, focusing on integrated weed management adapted to the specific habitat where the species causes damage—arable land, semi-natural vegetation, urban areas, or along linear infrastructures. A range of management methods is reviewed, including agrotechnical, mechanical, physical, thermal, biological, and chemical approaches. Particular attention is given to the spread of herbicide resistance and the need for diversified, habitat-specific interventions. Among biological control options, the potential of Ophraella communa LeSage, a leaf beetle native to North America, is highlighted. Furthermore, innovative technologies such as UAV-assisted weed mapping, site-specific herbicide application, and autonomous weeding robots are discussed as environmentally sustainable tools. The role of legal regulations and pollen monitoring networks—particularly those implemented in Hungary—is also emphasized. By combining traditional and advanced methods within a coordinated framework, effective and ecologically sound ragweed control can be achieved. Full article
(This article belongs to the Section Weed Science and Weed Management)
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20 pages, 1227 KiB  
Article
Interleukin Dynamics and Their Correlation with Tumor Aggressiveness in Colorectal Carcinoma
by Elena-Teodora Tâlvan, Liviuta Budișan, Călin Ilie Mohor, Valentin Grecu, Ioana Berindan-Neagoe, Victor Cristea, George Oprinca and Adrian Cristian
Int. J. Mol. Sci. 2025, 26(14), 7027; https://doi.org/10.3390/ijms26147027 - 21 Jul 2025
Viewed by 543
Abstract
Colorectal cancer (CRC) is a major global health concern, with tumor progression closely influenced by inflammatory mechanisms and cytokine signaling. This study investigates the serum expression levels of interleukins IL-8, IL-17A, and IL-33 in patients with colon cancer, analyzing their association with tumor [...] Read more.
Colorectal cancer (CRC) is a major global health concern, with tumor progression closely influenced by inflammatory mechanisms and cytokine signaling. This study investigates the serum expression levels of interleukins IL-8, IL-17A, and IL-33 in patients with colon cancer, analyzing their association with tumor grade and depth of invasion. The cohort included 42 patients stratified by tumor differentiation (G1–G3) and various invasion types. ELISA assays revealed that IL-8 levels were highest in well-differentiated tumors and in cases of submucosal and serosal invasion, suggesting a key role in early stage inflammation and angiogenesis. IL-17A and IL-33 levels declined progressively with tumor dedifferentiation and increased invasion depth, indicating immune suppression in advanced stages. Multiple regression analyses highlighted a nonlinear, significant relationship between IL-8 and IL-17A, whereas IL-33 showed no direct correlation with other interleukins. A combined model incorporating IL-8, IL-17A, IL-33, and tumor grade accounted for over 70% of IL-17A variability, underscoring their interactive role in CRC biology. These findings support the potential utility of interleukins as biomarkers and therapeutic targets for stratified CRC management. Full article
(This article belongs to the Special Issue Molecular Diagnosis and Treatment of Colorectal Cancer)
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32 pages, 8017 KiB  
Article
Tumor Organoids Grown in Mixed-Composition Hydrogels Recapitulate the Plasticity of Pancreatic Cancers
by Ioritz Sorzabal-Bellido, Xabier Morales, Iván Cortés-Domínguez, Maider Esparza, Lucía Grande, Pedro Castillo, Silvia Larumbe, María Monteserín, Shruthi Narayanan, Mariano Ponz-Sarvise, Silve Vicent and Carlos Ortiz-de-Solórzano
Gels 2025, 11(7), 562; https://doi.org/10.3390/gels11070562 - 21 Jul 2025
Viewed by 541
Abstract
Pancreatic ductal adenocarcinoma (PDAC) tumors exhibit pronounced phenotypic plasticity, alternating between a treatment-sensitive classical phenotype and a more aggressive basal-like state associated with drug resistance and poor prognosis. The frequent coexistence of these phenotypes complicates patient stratification and the selection of effective therapies. [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) tumors exhibit pronounced phenotypic plasticity, alternating between a treatment-sensitive classical phenotype and a more aggressive basal-like state associated with drug resistance and poor prognosis. The frequent coexistence of these phenotypes complicates patient stratification and the selection of effective therapies. Tumor-derived organoids are valuable tools for drug screening; however, their clinical relevance relies on how accurately they recapitulate the phenotypic and functional characteristics of the original tumors. In this study, we present a quantitative analysis of how hydrogel composition influences the phenotype, tissue remodeling, metabolism, and drug resistance of PDAC organoids. Organoids were cultured within three types of hydrogels: Matrigel, collagen-I, and a mixture of collagen-I and Matrigel. Our results demonstrate that: (i) PDAC organoids grown in Matrigel exhibit a classical phenotype, with metabolic and drug response profiles similar to those of low-physiological two-dimensional cultures; (ii) Organoids grown in collagen-containing hydrogels, particularly those in collagen-Matrigel composites, faithfully recapitulate basal-like tumors, characterized by epithelial-to-mesenchymal transition, tissue remodeling, metabolic activity, and drug resistance; (iii) TGFβ induces an exacerbated, highly invasive basal-like phenotype. Summarizing, our findings highlight the importance of 3D hydrogel composition in modulating PDAC organoid phenotype and behavior and suggest collagen-Matrigel hydrogels as the most suitable matrix for modeling PDAC biology. Full article
(This article belongs to the Special Issue Biobased Gels for Drugs and Cells)
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20 pages, 4705 KiB  
Article
GRK5 as a Novel Therapeutic Target for Immune Evasion in Testicular Cancer: Insights from Multi-Omics Analysis and Immunotherapeutic Validation
by Congcong Xu, Qifeng Zhong, Nengfeng Yu, Xuqiang Zhang, Kefan Yang, Hao Liu, Ming Cai and Yichun Zheng
Biomedicines 2025, 13(7), 1775; https://doi.org/10.3390/biomedicines13071775 - 21 Jul 2025
Viewed by 379
Abstract
Background: Personalized anti-tumor therapy that activates the immune response has demonstrated clinical benefits in various cancers. However, its efficacy against testicular cancer (TC) remains uncertain. This study aims to identify suitable patients for anti-tumor immunotherapy and to uncover potential therapeutic targets in TC [...] Read more.
Background: Personalized anti-tumor therapy that activates the immune response has demonstrated clinical benefits in various cancers. However, its efficacy against testicular cancer (TC) remains uncertain. This study aims to identify suitable patients for anti-tumor immunotherapy and to uncover potential therapeutic targets in TC for the development of tailored anti-tumor immunotherapy. Methods: Consensus clustering analysis was conducted to delineate immune subtypes, while weighted gene co-expression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) regression, and support vector machine (SVM) algorithms were employed to evaluate the potential efficacy of anti-tumor immunotherapy. Candidate immunotherapy targets were systematically identified through multi-gene panel analyses and subsequently validated using molecular biology assays. A prioritized target emerging from cellular screening was further evaluated for its capacity to potentiate anti-tumor immunity. The therapeutic efficacy of this candidate was rigorously confirmed through a comprehensive suite of immunological experiments. Results: Following systematic screening of five candidate genes (WNT11, FAM181B, GRK5, FSCN1, and ECHS1), GRK5 emerged as a promising therapeutic target for immunotherapy based on its distinct functional and molecular associations with immune evasion mechanisms. Cellular functional assays revealed that GRK5 knockdown significantly attenuated the malignant phenotype of testicular cancer cells, as evidenced by reduced proliferative capacity and invasive potential. Complementary immunological validation established that specific targeting of GRK5 with the selective antagonist GRK5-IN-2 disrupts immune evasion pathways in testicular cancer, as quantified by T-cell-mediated cytotoxicity. Conclusions: These findings position GRK5 as a critical modulator of tumor-immune escape, warranting further preclinical exploration of GRK5-IN-2 as a candidate immunotherapeutic agent. Full article
(This article belongs to the Section Immunology and Immunotherapy)
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41 pages, 2822 KiB  
Review
Sirtuins in Central Nervous System Tumors—Molecular Mechanisms and Therapeutic Targeting
by Agnieszka Nowacka, Martyna Śniegocka, Maciej Śniegocki and Ewa Aleksandra Ziółkowska
Cells 2025, 14(14), 1113; https://doi.org/10.3390/cells14141113 - 19 Jul 2025
Viewed by 931
Abstract
Sirtuins (SIRTs), a family of NAD+-dependent enzymes, play crucial roles in epigenetic regulation, metabolism, DNA repair, and stress response, making them relevant to glioma biology. This review systematically summarizes the molecular mechanisms and context-specific functions of SIRT1–SIRT7 in central nervous system tumors, with [...] Read more.
Sirtuins (SIRTs), a family of NAD+-dependent enzymes, play crucial roles in epigenetic regulation, metabolism, DNA repair, and stress response, making them relevant to glioma biology. This review systematically summarizes the molecular mechanisms and context-specific functions of SIRT1–SIRT7 in central nervous system tumors, with particular focus on gliomas. SIRT1, SIRT3, SIRT5, and SIRT7 are often overexpressed and promote glioma cell proliferation, stemness, therapy resistance, and metabolic adaptation. Conversely, SIRT2, SIRT4, and SIRT6 generally exhibit tumor-suppressive functions by inducing apoptosis, inhibiting invasion, and counteracting oncogenic signaling. Preclinical studies have identified several sirtuin modulators—both inhibitors and activators—that alter tumor growth, sensitize cells to temozolomide, and regulate pathways such as JAK2/STAT3, NF-κB, and mitochondrial metabolism. Emerging evidence positions sirtuins as promising targets for glioma therapy. Future studies should evaluate sirtuin modulators in clinical trials and explore their potential for patient stratification and combined treatment strategies. Full article
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25 pages, 3050 KiB  
Review
REG3A: A Multifunctional Antioxidant Lectin at the Crossroads of Microbiota Regulation, Inflammation, and Cancer
by Jamila Faivre, Hala Shalhoub, Tung Son Nguyen, Haishen Xie and Nicolas Moniaux
Cancers 2025, 17(14), 2395; https://doi.org/10.3390/cancers17142395 - 19 Jul 2025
Viewed by 509
Abstract
REG3A, a prominent member of the human regenerating islet-derived (REG) lectin family, plays a pivotal and multifaceted role in immune defense, inflammation, and cancer biology. Primarily expressed in gastrointestinal epithelial cells, REG3A reinforces barrier integrity, orchestrates mucosal immune responses, and regulates host–microbiota interactions. [...] Read more.
REG3A, a prominent member of the human regenerating islet-derived (REG) lectin family, plays a pivotal and multifaceted role in immune defense, inflammation, and cancer biology. Primarily expressed in gastrointestinal epithelial cells, REG3A reinforces barrier integrity, orchestrates mucosal immune responses, and regulates host–microbiota interactions. It also functions as a potent non-enzymatic antioxidant, protecting tissues from oxidative stress. REG3A expression is tightly regulated by inflammatory stimuli and is robustly induced during immune activation, where it limits microbial invasion, dampens tissue injury, and promotes epithelial repair. Beyond its antimicrobial and immunomodulatory properties, REG3A contributes to the resolution of inflammation and the maintenance of tissue homeostasis. However, its role in cancer is highly context-dependent. In some tumor types, REG3A fosters malignant progression by enhancing cell survival, proliferation, and invasiveness. In others, it acts as a tumor suppressor, inhibiting growth and metastatic potential. These opposing effects are likely dictated by a combination of factors, including the tissue of origin, the composition and dynamics of the tumor microenvironment, and the stage of disease progression. Additionally, the secreted nature of REG3A implies both local and systemic effects, further modulated by organ-specific physiology. Experimental variability may also reflect differences in methodologies, analytical tools, and model systems used. This review synthesizes current knowledge on the pleiotropic functions of REG3A, emphasizing its roles in epithelial defense, immune regulation, redox homeostasis, and oncogenesis. A deeper understanding of REG3A’s pleiotropic effects could open up new therapeutic avenues in both inflammatory disorders and cancer. Full article
(This article belongs to the Special Issue Lectins in Cancer)
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15 pages, 1398 KiB  
Article
Lymphovascular Invasion Is a Predictor of Clinical Outcomes in Bladder Cancer Patients Treated with Radical Cystectomy
by Daniel-Vasile Dulf, Anamaria Larisa Burnar, Patricia-Lorena Dulf, Doina-Ramona Matei, Raluca Maria Hendea, Iulia Andraș, Miruna Grecea, Cătălina Bungărdean, Antonio De Leo, Tudor-Eliade Ciuleanu, Nicolae Crișan and Camelia Alexandra Coada
J. Clin. Med. 2025, 14(14), 5120; https://doi.org/10.3390/jcm14145120 - 18 Jul 2025
Viewed by 344
Abstract
Background/Objectives: Lymphovascular invasion (LVI) has been consistently linked to poor outcomes in patients with bladder cancer (BC), yet its independent prognostic value, especially after adjusting for established pathological features, remains debated. This study aimed to evaluate the prognostic value of LVI in the [...] Read more.
Background/Objectives: Lymphovascular invasion (LVI) has been consistently linked to poor outcomes in patients with bladder cancer (BC), yet its independent prognostic value, especially after adjusting for established pathological features, remains debated. This study aimed to evaluate the prognostic value of LVI in the context of other pathological features of patients undergoing radical cystectomy. Methods: We conducted a retrospective cohort study including 200 patients treated at the Municipal Clinical Hospital in Cluj-Napoca, Romania. Associations between LVI and overall survival (OS) were assessed using univariable and multivariable Cox proportional hazards models, with Kaplan–Meier curves used for visualizing survival distributions. Results: In univariable analysis, increasing age, presence of LVI, advanced pathological tumor stage (pT ≥ 2), and nodal involvement (pN ≥ 1) were significantly associated with worse OS. LVI was a strong predictor of poor survival (HR 3.13; 95% CI: 2.09; 4.69; p < 0.001). However, in multivariable analysis, only tumor stage (HR 4.85; 95% CI: 2.19; 10.77; p < 0.001) and nodal involvement (HR 1.87; 95% CI: 1.13; 3.09; p = 0.015) remained independently associated with OS. In patients with incomplete nodal staging (Nx), LVI was significantly associated with OS (p = 0.028). Conclusions: Our findings reinforce the prognostic relevance of LVI in bladder cancer and support its role as a marker of aggressive tumor biology, highlighting its value in clinical risk assessment, especially in patients with incomplete nodal staging. Routine reporting of LVI in pathology and consideration in treatment planning are warranted. Full article
(This article belongs to the Special Issue Advances and Perspectives in Cancer Diagnostics and Treatment)
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