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26 pages, 5572 KB  
Article
Targeting GPR55 with Cannabidiol Derivatives: A Molecular Docking Approach Toward Novel Neurotherapeutics
by Catalina Mares, Andra-Maria Paun, Maria Mernea, Cristina Matanie and Speranta Avram
Processes 2025, 13(10), 3261; https://doi.org/10.3390/pr13103261 (registering DOI) - 13 Oct 2025
Abstract
This study investigated the interaction between cannabidiol (CBD) derivatives and the GPR55 receptor using a bioinformatics-driven molecular docking approach. GPR55, implicated in central nervous system (CNS) pathologies, represents a promising target for novel therapeutics. Drug-likeness evaluation via SwissADME confirmed that all selected derivatives [...] Read more.
This study investigated the interaction between cannabidiol (CBD) derivatives and the GPR55 receptor using a bioinformatics-driven molecular docking approach. GPR55, implicated in central nervous system (CNS) pathologies, represents a promising target for novel therapeutics. Drug-likeness evaluation via SwissADME confirmed that all selected derivatives complied with Lipinski′s Rule of Five, exhibiting favorable physicochemical properties with molecular weights below 500 Da and acceptable logP values. Molecular docking simulations, performed using AutoDock Vina through PyRx, revealed strong binding affinities, with docking scores ranging from −9.2 to −7.2 kcal/mol, indicating thermodynamically feasible interactions. Visualization and interaction analysis identified a conserved binding pocket involving key residues, including TYR101, PHE102, TYR106, ILE156, PHE169, MET172, TRP177, PRO184, LEU185, LEU270 and MET274. Ligand clustering in this region further supports the presence of a structurally defined binding site. Molecular dynamics simulations of GPR55 in complex with the three top-scoring ligands (3″-HOCBD, THC, and CBL) revealed that all ligands remained stably bound within the cavity over 100 ns, with ligand-specific rearrangements. Predicted oral bioavailability was moderate (0.55), consistent with the need for optimized formulations to enhance systemic absorption. These findings suggest that CBD derivatives may act as potential modulators of GPR55, offering a basis for the development of novel CNS-targeted therapeutics. Full article
(This article belongs to the Section Biological Processes and Systems)
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15 pages, 3412 KB  
Article
Reconstruction Fidelity of Acoustic Holograms Across 0.75–4.0 MHz Excitation Frequencies: A Simulation Study
by Haseeb Khan and Jinwook Kim
Appl. Sci. 2025, 15(20), 10991; https://doi.org/10.3390/app152010991 (registering DOI) - 13 Oct 2025
Abstract
Accurate reconstruction of pressure fields using phase-only acoustic holograms is critical for applications requiring high spatial precision, such as targeted ultrasound therapies. In this study, we investigate the effect of excitation frequency on reconstruction accuracy by performing a controlled sweep from 0.75 to [...] Read more.
Accurate reconstruction of pressure fields using phase-only acoustic holograms is critical for applications requiring high spatial precision, such as targeted ultrasound therapies. In this study, we investigate the effect of excitation frequency on reconstruction accuracy by performing a controlled sweep from 0.75 to 4.0 MHz, while keeping all other parameters such as aperture size, simulation grid, target patterns, and optimization settings constant. To evaluate performance, we employ five quantitative metrics: Mean Squared Error (MSE), Peak Signal-to-Noise Ratio (PSNR), Cross-Correlation, Uniformity, and Efficiency. The results show that reconstruction fidelity improves as frequency increases, particularly in the low-to-mid range, where finer spatial features become resolvable due to the shorter wavelengths. However, beyond a certain point, the gains begin to taper, and in some cases, high frequencies introduce subtle artifacts such as edge ringing or increased variance. Moreover, higher frequencies are associated with increased acoustic attenuation and imposing stricter fabrication demands on holographic elements. These findings suggest that frequency selection in acoustic holography must be application-specific, as both low and high frequencies offer distinct advantages depending on the target characteristics and system constraints. Full article
22 pages, 1482 KB  
Article
Cellular eEF1G Inhibits Porcine Deltacoronavirus Replication by Binding Nsp12 and Disrupting Its Interaction with Viral Genomic RNA
by Weijia Yin, Xinna Ge, Lei Zhou, Xin Guo, Jun Han, Yongning Zhang and Hanchun Yang
Viruses 2025, 17(10), 1369; https://doi.org/10.3390/v17101369 (registering DOI) - 13 Oct 2025
Abstract
Porcine deltacoronavirus (PDCoV) is an emerging pathogen that causes severe, often fatal, diarrhea in suckling piglets and has zoonotic potential. Its nonstructural protein 12 (Nsp12), functioning as the RNA-dependent RNA polymerase (RdRp), is a central component of the viral replication–transcription complex and a [...] Read more.
Porcine deltacoronavirus (PDCoV) is an emerging pathogen that causes severe, often fatal, diarrhea in suckling piglets and has zoonotic potential. Its nonstructural protein 12 (Nsp12), functioning as the RNA-dependent RNA polymerase (RdRp), is a central component of the viral replication–transcription complex and a critical target for host antiviral mechanisms. Here, we identified eukaryotic elongation factor 1 gamma (eEF1G) as a host interactor of PDCoV Nsp12 by immunoprecipitation-coupled mass spectrometry in IPEC-J2 cells. This interaction was confirmed by co-immunoprecipitation, pull-down assays, and confocal microscopy. Functional analyses involving siRNA knockdown and overexpression of eEF1G, combined with viral titration, strand-specific real-time quantitative PCR, and RNA immunoprecipitation assays, demonstrated that eEF1G directly binds to Nsp12. Knockdown of eEF1G significantly enhanced viral replication and increased negative-stranded RNA synthesis, whereas overexpression did not affect viral proliferation. Furthermore, eEF1G was found to bind PDCoV genomic RNA and competitively disrupt the interaction between Nsp12 and viral RNA, thereby impairing RdRp activity. Our results indicate that eEF1G acts as a novel host restriction factor that inhibits PDCoV replication by competing with Nsp12 for genomic RNA binding, ultimately blocking negative-stranded RNA synthesis. This study unveils a new antiviral mechanism and highlights a potential target for developing interventions against PDCoV. Full article
(This article belongs to the Special Issue Porcine Viruses 2025)
17 pages, 1517 KB  
Article
Cytokine Profile and Oxidative Patterns in Murine Models of Disseminated Infection by Mucorales Species
by Hiram Villanueva-Lozano, Martín García-Juárez, Adrián G. Rosas-Taraco, Rogelio de J. Treviño-Rangel and Gloria M. González
Pathogens 2025, 14(10), 1036; https://doi.org/10.3390/pathogens14101036 (registering DOI) - 13 Oct 2025
Abstract
Mucormycosis is a life-threatening infection caused by fungi of the Mucorales order, typically associated with immunocompromised hosts, but increasingly reported in immunocompetent individuals. This study investigated fungal burden, Th1/Th17 inflammatory profiles, and organ-specific dynamics in immunocompetent BALB/c mice intravenously infected with Rhizopus oryzae [...] Read more.
Mucormycosis is a life-threatening infection caused by fungi of the Mucorales order, typically associated with immunocompromised hosts, but increasingly reported in immunocompetent individuals. This study investigated fungal burden, Th1/Th17 inflammatory profiles, and organ-specific dynamics in immunocompetent BALB/c mice intravenously infected with Rhizopus oryzae, Mucor circinelloides, or Rhizomucor pusillus. Colony-forming units were quantified in spleen, liver, and kidney at multiple time points, while serum cytokines and oxidative stress markers were analyzed. The results showed fungal persistence primarily in the spleen, accompanied by species-specific Th1/Th17 responses: R. oryzae induced the highest inflammatory response among all groups, with maximal cytokine production observed on day 7, particularly for IL-17A (352.58 pg/mL). In contrast, M. circinelloides exhibited its peak cytokine levels earlier, reaching the highest TNF-α concentration on day 3 (425.43 pg/mL). Meanwhile, R. pusillus triggered an early but moderate inflammatory response, with a maximum TNF-α value of 372.62 pg/mL detected on day 1, followed by clearance. Correlation analysis highlighted distinct immunological patterns, with IL-10 acting as a negative regulator of inflammation, while TNF-α and IL-17A reflected infection intensity depending on species and timing. The spleen emerged as a key organ coordinating immune responses during systemic infection. These findings reveal that mucormycosis in immunocompetent hosts triggers complex, species-dependent immune dynamics beyond classical immunosuppression, emphasizing the need to consider host–pathogen interactions when developing targeted antifungal strategies. Full article
(This article belongs to the Section Fungal Pathogens)
17 pages, 5090 KB  
Article
An Off-Axis Catadioptric Division of Aperture Optical System for Multi-Channel Infrared Imaging
by Jie Chen, Tong Yang, Hongbo Xie and Lei Yang
Photonics 2025, 12(10), 1008; https://doi.org/10.3390/photonics12101008 (registering DOI) - 13 Oct 2025
Abstract
Multi-channel optical systems can provide more feature information compared to single-channel systems, making them valuable for optical remote sensing, target identification, and other applications. The division of aperture polarization imaging modality allows for the simultaneous imaging of targets in the same field of [...] Read more.
Multi-channel optical systems can provide more feature information compared to single-channel systems, making them valuable for optical remote sensing, target identification, and other applications. The division of aperture polarization imaging modality allows for the simultaneous imaging of targets in the same field of view with a single detector. To overcome the limitations of conventional refractive aperture-divided systems for miniaturization, this work proposes an off-axis catadioptric aperture-divided technique for polarization imaging. First, the design method of the off-axis reflective telescope structure is discussed. The relationship between optical parameters such as magnification, surface coefficient, and primary aberration is studied. Second, by establishing the division of the aperture optical model, the method of maximizing the field of view and aperture is determined. Finally, an off-axis catadioptric cooled aperture-divided infrared optical system with a single aperture focal length of 60 mm is shown as a specific design example. Each channel can achieve 100% cold shield efficiency, and the overall length of the telescope module can be decreased significantly. The image quality of each imaging channel is close to the diffraction limit, verifying the effectiveness and feasibility of the method. The proposed off-axis catadioptric aperture-divided design method holds potential applications in simultaneous infrared polarization imaging. Full article
(This article belongs to the Section Optical Interaction Science)
18 pages, 1310 KB  
Article
Plasma with Added Protease Inhibitors Improves Alpha- and Beta-CGRP Measurement Compared to Serum: Towards a Reliable Biomarker for Chronic Migraine
by Lucía de la Guerra-Sasián, Gabriel Gárate, Jorge Madera, Sara Pérez-Pereda, Marta Pascual-Mato, Vicente González-Quintanilla, Julio Pascual and María Muñoz-San Martín
Int. J. Mol. Sci. 2025, 26(20), 9958; https://doi.org/10.3390/ijms26209958 (registering DOI) - 13 Oct 2025
Abstract
The neuropeptide calcitonin gene-related peptide (CGRP), especially a-CGRP, is central in migraine pathophysiology. Although CGRP is a therapeutic target and potential biomarker, inconsistencies in measurement procedures need to be further studied for reliable results. This study aims to analyze factors influencing plasma CGRP [...] Read more.
The neuropeptide calcitonin gene-related peptide (CGRP), especially a-CGRP, is central in migraine pathophysiology. Although CGRP is a therapeutic target and potential biomarker, inconsistencies in measurement procedures need to be further studied for reliable results. This study aims to analyze factors influencing plasma CGRP measurement. Chronic migraine (CM) patients were recruited in our Headache Unit. Blood samples were collected before and during treatment with CGRP monoclonal antibodies, processed and stored. Levels of CGRP were measured with isoform-specific enzyme-linked immunosorbent assay (ELISA) tests. Statistical tests were used to assess concentration changes and group differences. The addition of protease inhibitors (PIs) to plasma samples significantly increased a-CGRP level detection, with a smaller effect on β-CGRP. No correlation was found between the a- and β-CGRP levels in plasma. The plasma-PI samples showed higher CGRP concentrations than in serum. The a-CGRP levels decreased during treatment while the β-CGRP levels remained stable. a-CGRP and age correlated negatively, but no sex-related differences were observed either for a- or β-CGRP. PI improved CGRP detection in plasma. The a-CGRP levels, which were influenced by age, decreased with specific treatment, suggesting its potential role as a biomarker. In contrast, β-CGRP remained stable, suggesting independent regulation of both isoforms. Full article
(This article belongs to the Section Biochemistry)
21 pages, 2459 KB  
Article
Phenolic Derivatives of Astragalus Aitosensis with Selective MAO-B Inhibition and Mitochondrial Protection
by Preslav Enchev, Magdalena Kondeva-Burdina, Emilio Mateev, Iliana Ionkova and Yancho Zarev
Molecules 2025, 30(20), 4069; https://doi.org/10.3390/molecules30204069 (registering DOI) - 13 Oct 2025
Abstract
Astragalus aitosensis, also known as Astracantha arnacantha (M. Bieb.) Podlech subsp. aitosensis (Ivanisch.) Réer & Podlech, a Bulgarian endemic species, was investigated for its phenolic profile and neuroprotective potential. A targeted extraction approach led to the isolation of 14 phytochemicals. According to [...] Read more.
Astragalus aitosensis, also known as Astracantha arnacantha (M. Bieb.) Podlech subsp. aitosensis (Ivanisch.) Réer & Podlech, a Bulgarian endemic species, was investigated for its phenolic profile and neuroprotective potential. A targeted extraction approach led to the isolation of 14 phytochemicals. According to our literature review, none of the isolated chemicals have been reported before for A. aitosensis. Two of them are previously undescribed molecules—an isomer of odoratin and 6-hydroxy-3-(2-hydroxy-4-methoxyphenyl)-7-methoxy-4H-1-benzopyran-4-one—and four of them had not been observed before our study in the genus Astragalus: 3′-methoxydaidzein, fujikinetin, sayanedine, and 6,4′-dimethoxy-7,2′-dihydroxyisoflavone. Five of the phytochemicals—maackiain, cajanin, onogenin, afrormosin, and sayanedine—exhibited selective inhibition of human monoamine oxidase-B (MAO-B), with maackiain reducing activity by 45%, nearing the effect of selegiline. The investigated phytochemicals also showed significant antioxidant and neuroprotective effects in ex vivo models using isolated rat brain synaptosomes, mitochondria, and microsomes, mitigating oxidative stress by preserving glutathione levels and reducing lipid peroxidation. Molecular docking confirmed favorable binding of active phytochemicals, particularly maackiain, within the MAO-B active site. Structure–activity relationship (SAR) analysis highlighted the role of specific substituents and fused-ring systems in MAO-B inhibition. This study expands our knowledge of the phytochemical diversity of A. aitosensis and supports the therapeutic relevance of its phenolic compounds in neurodegenerative disorders such as Parkinson’s disease. Full article
11 pages, 416 KB  
Article
The Clinical and Diagnostic Characterization of 6q24-Related Transient Neonatal Diabetes Mellitus: A Polish Pediatric Cohort Study
by Michał Pietrusiński, Julia Grzybowska-Adamowicz, Tomasz Płoszaj, Sebastian Skoczylas, Maciej Borowiec, Katarzyna Piekarska, Bogda Skowrońska, Małgorzata Wajda-Cuszlag, Artur Mazur and Agnieszka Zmysłowska
Biomedicines 2025, 13(10), 2492; https://doi.org/10.3390/biomedicines13102492 (registering DOI) - 13 Oct 2025
Abstract
Background/Objectives: Transient neonatal diabetes mellitus (TNDM) is a form of neonatal diabetes mellitus (NDM) arising in the first weeks of life and remitting in infancy. Epigenetic aberrations at the imprinted 6q24 locus (overexpression of PLAGL1/HYMAI) are the most common causes [...] Read more.
Background/Objectives: Transient neonatal diabetes mellitus (TNDM) is a form of neonatal diabetes mellitus (NDM) arising in the first weeks of life and remitting in infancy. Epigenetic aberrations at the imprinted 6q24 locus (overexpression of PLAGL1/HYMAI) are the most common causes of TNDM. The aim of this study was a retrospective clinical and genetic analysis of a Polish pediatric cohort, emphasizing the role of methylation-specific MLPA (MS-MLPA) in the diagnosis of TNDM. Methods: We conducted a retrospective analysis of the medical records of 22 patients with diabetes diagnosed at 1 year of age. The molecular studies included an analysis of the NDM gene panel by a targeted NGS and MS-MLPA for the 6q24 imprinting region. Results: 6q24-TNDM was confirmed in five patients, with a median age of diabetes remission of 4 months (IQR: 3–6 months). The MS-MLPA identified paternal UPD6 or isolated maternal hypomethylation of PLAGL1 in three patients, and two had a paternal 6q24 duplication. Conclusions: In our group, changes in the 6q24 region were confirmed in 22.7% of NDM patients, indicating the usefulness of the MS-MLPA technique in the diagnosis and detection of imprinting defects. We acknowledge key limitations, including diagnostic delays and incomplete parental testing, which precluded trio-based confirmation of paternal UPD6 versus epimutation in some cases; future diagnostic workflows should incorporate an early trio-based SNP array or STR confirmation. A methylation analysis should be included early in the NDM genetic diagnosis process to provide genetic counseling and monitor patients for diabetes recurrence. Full article
(This article belongs to the Special Issue Molecular and Cellular Research in Diabetes and Metabolic Diseases)
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29 pages, 1315 KB  
Review
Targeting the Eye: RNA-Based Therapies, Interferences, and Delivery Strategies
by Mohammed S. Abdel-Raziq Hassan, Cheng Zhong, Fatma Hassan and S. Kevin Li
Pharmaceutics 2025, 17(10), 1326; https://doi.org/10.3390/pharmaceutics17101326 - 13 Oct 2025
Abstract
Recent advances in molecular biology have led to the development of RNA-based therapeutics, offering significant promise for treating various eye diseases. Current RNA therapeutics include RNA aptamers, antisense oligonucleotides (ASOs), small interfering RNA (siRNA), and messenger RNA (mRNA) that can target specific genetic [...] Read more.
Recent advances in molecular biology have led to the development of RNA-based therapeutics, offering significant promise for treating various eye diseases. Current RNA therapeutics include RNA aptamers, antisense oligonucleotides (ASOs), small interfering RNA (siRNA), and messenger RNA (mRNA) that can target specific genetic and molecular pathways involved in eye disorders. In addition to their potential in therapy, RNA technologies have also provided tools for mechanistic studies to improve the understanding of eye diseases, expanding the possibilities of RNA-based treatments. Despite the utility of RNA in studying eye disease mechanisms and its potential in disease treatment, only a few RNA-based therapies have been approved for posterior eye diseases. This paper reviews RNA interference and related ocular delivery and posterior eye diseases, focusing on the use of RNA aptamers, siRNA, short hairpin RNA (shRNA), and microRNA (miRNA). Approaches using RNA to advance our understanding of eye diseases and disease treatments, particularly in the posterior segment of the eye, are discussed. It is concluded that RNA therapeutics offer a novel approach to treating a variety of eye diseases by targeting their molecular causes. siRNA, shRNA, miRNA, and ASO can directly silence disease-driving genes, while RNA aptamers bind to specific targets. Although many RNA-based therapies are still in experimental stages, they hold promise for conditions such as age-related macular degeneration (AMD), diabetic macular edema (DME), glaucoma, and inherited retinal disorders. Effective delivery methods and long-term safety are key challenges that need to be addressed for these treatments to become widely available. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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31 pages, 1305 KB  
Review
Artificial Intelligence in Cardiac Electrophysiology: A Clinically Oriented Review with Engineering Primers
by Giovanni Canino, Assunta Di Costanzo, Nadia Salerno, Isabella Leo, Mario Cannataro, Pietro Hiram Guzzi, Pierangelo Veltri, Sabato Sorrentino, Salvatore De Rosa and Daniele Torella
Bioengineering 2025, 12(10), 1102; https://doi.org/10.3390/bioengineering12101102 - 13 Oct 2025
Abstract
Artificial intelligence (AI) is transforming cardiac electrophysiology across the entire care pathway, from arrhythmia detection on 12-lead electrocardiograms (ECGs) and wearables to the guidance of catheter ablation procedures, through to outcome prediction and therapeutic personalization. End-to-end deep learning (DL) models have achieved cardiologist-level [...] Read more.
Artificial intelligence (AI) is transforming cardiac electrophysiology across the entire care pathway, from arrhythmia detection on 12-lead electrocardiograms (ECGs) and wearables to the guidance of catheter ablation procedures, through to outcome prediction and therapeutic personalization. End-to-end deep learning (DL) models have achieved cardiologist-level performance in rhythm classification and prognostic estimation on standard ECGs, with a reported arrhythmia classification accuracy of ≥95% and an atrial fibrillation detection sensitivity/specificity of ≥96%. The application of AI to wearable devices enables population-scale screening and digital triage pathways. In the electrophysiology (EP) laboratory, AI standardizes the interpretation of intracardiac electrograms (EGMs) and supports target selection, and machine learning (ML)-guided strategies have improved ablation outcomes. In patients with cardiac implantable electronic devices (CIEDs), remote monitoring feeds multiparametric models capable of anticipating heart-failure decompensation and arrhythmic risk. This review outlines the principal modeling paradigms of supervised learning (regression models, support vector machines, neural networks, and random forests) and unsupervised learning (clustering, dimensionality reduction, association rule learning) and examines emerging technologies in electrophysiology (digital twins, physics-informed neural networks, DL for imaging, graph neural networks, and on-device AI). However, major challenges remain for clinical translation, including an external validation rate below 30% and workflow integration below 20%, which represent core obstacles to real-world adoption. A joint clinical engineering roadmap is essential to translate prototypes into reliable, bedside tools. Full article
(This article belongs to the Special Issue Mathematical Models for Medical Diagnosis and Testing)
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43 pages, 2880 KB  
Review
Relevance of AKT and RAS Signaling Pathways for Antibody–Drug Conjugate Immunotherapies in Acute Lymphoblastic Leukemia
by Patrick A. H. Ehm and Christoph Rehbach
Lymphatics 2025, 3(4), 33; https://doi.org/10.3390/lymphatics3040033 (registering DOI) - 13 Oct 2025
Abstract
Acute lymphoblastic leukemia is the most common cause of cancer-related death in children and represents a poor prognosis for patients in high-risk groups. Current treatment protocols are based on intensive polychemotherapy, which is associated with a significant toxicity profile. Due to their higher [...] Read more.
Acute lymphoblastic leukemia is the most common cause of cancer-related death in children and represents a poor prognosis for patients in high-risk groups. Current treatment protocols are based on intensive polychemotherapy, which is associated with a significant toxicity profile. Due to their higher specificity and lower toxicity, immunotherapies based on monoclonal antibodies, in particular antibody–drug conjugates (ADCs), are revolutionizing cancer therapy. However, reports on the potential efficacy of ADC-targeted therapy in ALL and its subgroups are limited. Gene expression data suggest that potentially new ADC antigens are highly abundant in ALL subgroups and represent promising targets for cancer therapy. In addition, the PI3K/AKT and RAS/MAPK signaling pathways are often persistently activated in ALL and recent data showed that active feedback loops following inhibition of these pathways can lead to redundancy of cell surface receptors that can potentially serve as antigens for ADC treatment. Therefore, we provide here an overview of the most interesting receptors of the various ALL subgroups and discuss the influence that feedback loops of the PI3K/AKT and RAS/MAPK signaling pathways may have on increasing protein expression of the aforementioned receptors, which could lead to targeted combination therapy approaches in the future. Full article
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27 pages, 4953 KB  
Article
Genome-Wide Analysis and Functional Correlation of Tomato JAZ Genes Under Tuta absoluta Infestation and Nanoparticle-Induced Defense
by Inzamam Ul Haq, Abdul Basit, Moazam Hyder, Mirza Naveed Shahzad, Asim Abbasi, Yasir Sharif, Muhammad Adeel Ghafar, Xiangyun Cai, Nazih Y. Rebouh and Youming Hou
Insects 2025, 16(10), 1046; https://doi.org/10.3390/insects16101046 - 13 Oct 2025
Abstract
Tomato (Solanum lycopersicum) production is increasingly threatened by Tuta absoluta, a destructive pest that compromises yield and quality. To explore sustainable alternatives to conventional insecticides, we investigated the jasmonate-mediated defense pathway by performing a genome-wide characterization of the JAZ gene [...] Read more.
Tomato (Solanum lycopersicum) production is increasingly threatened by Tuta absoluta, a destructive pest that compromises yield and quality. To explore sustainable alternatives to conventional insecticides, we investigated the jasmonate-mediated defense pathway by performing a genome-wide characterization of the JAZ gene family in S. lycopersicum. A total of 39 SlJAZ genes were identified and mapped to 12 chromosomes. Detailed analysis revealed conserved motifs, diverse exon–intron structures, four major phylogenetic groups, and the presence of multiple MeJA- and stress-responsive cis-elements. Synteny analysis indicated gene duplication events and evolutionary conservation with Arabidopsis and potato. Small RNA predictions suggested that 33 SlJAZ genes are targeted by 69 microRNAs, implying multilayered regulation. Transcriptome analysis under four treatment conditions—mesoporous silica nanoparticles (MSNs) ± pest infestation—revealed 21 differentially expressed SlJAZ genes. SlJAZ1, SlJAZ19, SlJAZ20, and SlJAZ22 were notably upregulated under the combined MSN and pest treatment, with expression patterns validated by qRT-PCR (R2 = 0.92). Phenotypic assessment of leaf damage index, larval survival rate, and number of leaf mines showed reduced pest activity in MSN-treated plants. Regression analysis demonstrated significant negative correlations between expression levels of SlJAZ20, SlJAZ26, and SlJAZ29 and pest-related damage traits. These findings indicate that MSNs function as effective elicitors of JA-responsive defense in tomato and modulate the expression of specific JAZ genes linked to enhanced resistance. The study provides a valuable foundation for integrating nanotechnology with molecular defense strategies to promote sustainable pest management. Full article
(This article belongs to the Special Issue Research on Insect Molecular Biology)
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12 pages, 865 KB  
Article
Genetic Variability in NKG2 Receptors and Their Ligands: Associations with SARS-CoV-2 Infection and COVID-19 Severity
by Jagoda Siemaszko, Katarzyna Grad, Jerzy Świerkot and Katarzyna Bogunia-Kubik
Genes 2025, 16(10), 1193; https://doi.org/10.3390/genes16101193 - 13 Oct 2025
Abstract
Background: The emergence of the COVID-19 pandemic has accelerated research into diverse immune response mechanisms. One key area of interest is the regulation of cytotoxic activity by Natural Killer (NK) cells. These cells rely on a dynamic interplay between activating and inhibitory surface [...] Read more.
Background: The emergence of the COVID-19 pandemic has accelerated research into diverse immune response mechanisms. One key area of interest is the regulation of cytotoxic activity by Natural Killer (NK) cells. These cells rely on a dynamic interplay between activating and inhibitory surface receptors that recognize specific ligands on target cells. Among these, receptors from the NKG2 family are particularly important, as maintaining their proper balance and function is essential for controlling NK cell cytotoxicity. Methods: In this study we employed qPCR to assess the genetic variability using single-nucleotide polymorphisms (SNPs) of NKG2A and NKG2D receptors and their ligands HLA-E and MICA/MICB. NKG2C deletion was determined by PCR-SSP, and serum-soluble levels of HLA-E and MICA/MICB molecules were measured by ELISA and Luminex methods. Results: Genotyping studies revealed that both NKG2A rs7301582 T and HLA-E rs1264457 A (HLA-E*01:01) alleles were predominant among infected individuals (OR = 2.21, p = 0.0258 and OR = 2.84, p = 0.0257, respectively). In contrast to MICB rs1065075 A, the MICA rs1051792 A (129Met) allele was most commonly found in hospitalized patients (OR = 14.95, p = 0.0114). The presence of the NKG2C del variant tended to be associated with an increased risk of SARS-CoV-2 infection (OR = 2.02, p = 0.0694). Moreover, higher concentrations of serum-soluble MICB was detected in infected individuals as compared to the control group (p = 0.008). Conclusions: Genetic variability of NK cell receptors and ligands as well as serum levels of their soluble forms showed associations with the risk of development of COVID-19 and the severity of its symptoms. Full article
(This article belongs to the Section Microbial Genetics and Genomics)
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23 pages, 1059 KB  
Review
Non-Protein-Coding RNA and Acute Kidney Injury: New Developments from Pathogenesis to Potential Biomarker
by Grazia Maria Virzì, Anna Clementi, Monica Zanella and Claudio Ronco
Genes 2025, 16(10), 1194; https://doi.org/10.3390/genes16101194 - 13 Oct 2025
Abstract
Acute Kidney Injury (AKI) is a critical medical condition characterized by a sudden and significant decline in renal function over a short timeframe. Commonly triggered by factors such as sepsis, ischemia–reperfusion injury, or nephrotoxic agents, AKI is linked to substantial rates of morbidity [...] Read more.
Acute Kidney Injury (AKI) is a critical medical condition characterized by a sudden and significant decline in renal function over a short timeframe. Commonly triggered by factors such as sepsis, ischemia–reperfusion injury, or nephrotoxic agents, AKI is linked to substantial rates of morbidity and mortality. In recent years, small non-coding RNAs have gained attention as promising biomarkers for the early diagnosis and potential treatment of AKI. Among them, microRNAs (miRNAs)—short RNA sequences of 21–25 nucleotides that regulate gene expression via sequence-specific binding—stand out due to their remarkable stability in biological fluids such as plasma and urine. Notably, certain miRNAs, including miR-21, miR-30, miR-494, and miR-29, have shown the ability to detect AKI earlier than traditional biomarkers like serum creatinine, offering the potential to enhance clinical decision-making. This narrative review aims to provide a comprehensive overview of the recent findings regarding the involvement of non-coding RNA, in particular microRNAs, in both the early diagnosis and therapeutic strategies for AKI. By highlighting their potential as sensitive biomarkers and novel treatment targets, this review seeks to contribute to advancing clinical approaches that improve patient outcomes. Ultimately, a deeper understanding and utilization of microRNAs could lead to the development of new diagnostic tools and targeted therapies for AKI, helping to prevent progression to chronic kidney disease and reduce associated mortality rates. However, further clinical studies and translational applications are still needed to validate these findings and implement them in patient care. Full article
(This article belongs to the Section RNA)
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22 pages, 2098 KB  
Review
Mammary Gland Microbiota in Benign Breast Diseases
by Nikita I. Ukraincev, Maria I. Kashutina, Larisa I. Kasatkina, Adkhamzhon B. Abduraimov and Yury V. Zhernov
Int. J. Mol. Sci. 2025, 26(20), 9951; https://doi.org/10.3390/ijms26209951 (registering DOI) - 13 Oct 2025
Abstract
The human microbiome is a critical factor in health and disease. While its association with breast cancer (BC) has been increasingly studied, this review provides a dedicated synthesis of the microbiota’s role in benign breast diseases (BBDs)—a common yet microbiologically overlooked spectrum of [...] Read more.
The human microbiome is a critical factor in health and disease. While its association with breast cancer (BC) has been increasingly studied, this review provides a dedicated synthesis of the microbiota’s role in benign breast diseases (BBDs)—a common yet microbiologically overlooked spectrum of conditions. The primary aim of this work is to consolidate the current understanding of the composition, origins, and functional mechanisms of the mammary gland (MG) microbiota specifically in the context of BBD and to evaluate its potential for novel diagnostic and therapeutic targets. We detail the distinct MG microbiota, formed via exogenous (e.g., cutaneous, translocation) and endogenous (e.g., enteromammary, lymphohematogenous) pathways, and its interaction with the host through estrogen metabolism, immunomodulation, and epigenetic modifications. This narrative review reveals unique dysbiotic patterns in BBD, characterized by distinct microbial signatures, such as the enrichment of Corynebacterium kroppenstedtii in granulomatous mastitis and the presence of Staphylococcus aureus in fibroadenomas and lactational mastitis. Furthermore, specific gut microbial profiles are identified in BBD patients, including an increased abundance of genera such as Clostridium and Faecalibacterium, alongside a decrease in Collinsella and Alistipes compared to healthy controls. These specific taxa represent compelling candidates for diagnostic biomarkers. We conclude that microbial dysbiosis is a significant component of BBD pathogenesis. A paradigm shift toward multi-omics approaches and mechanistic studies is now essential to translate these associations into clinical applications. Understanding the BBD-specific microbiome holds the promise of revolutionizing patient care through microbiota-based diagnostics for differentiating benign subtypes and novel, personalized therapeutic strategies aimed at restoring microbial homeostasis. Full article
(This article belongs to the Section Molecular Microbiology)
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