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16 pages, 2474 KiB  
Article
Structural and Functional Assessment of the Macular Inner Retinal Layers in Multiple Sclerosis Eyes Without History of Optic Neuropathy
by Lucilla Barbano, Lucia Ziccardi, Carmen Dell'Aquila, Mattia D’Andrea, Carolina Gabri Nicoletti, Doriana Landi, Giorgia Mataluni, Antonio Di Renzo, Fabio Buttari, Roberto dell'Omo, Girolama Alessandra Marfia, Diego Centonze and Vincenzo Parisi
J. Clin. Med. 2025, 14(16), 5919; https://doi.org/10.3390/jcm14165919 (registering DOI) - 21 Aug 2025
Abstract
Background: Considering the lack of studies regarding the localized evaluation of the macular inner retina in multiple sclerosis patients without optic neuritis (MSnoON eyes), we investigated the structure and function of retinal ganglion cells (RGCs) located in different macular areas. Methods: [...] Read more.
Background: Considering the lack of studies regarding the localized evaluation of the macular inner retina in multiple sclerosis patients without optic neuritis (MSnoON eyes), we investigated the structure and function of retinal ganglion cells (RGCs) located in different macular areas. Methods: In 24 MSnoON patients (mean age: 45.22 ± 5.57 years; 14 females and 10 males; mean MS disease duration: 11.07 ± 5.88 years) and in 30 age-similar (mean age: 45.09 ± 5.08 years) control subjects, complete ophthalmological examination, optical coherence tomography (OCT) and multifocal photopic negative response (mfPhNR) were performed. The ganglion cell layer thickness (GCL+-T) via OCT and the response amplitude density (RAD) through mfPhNR were measured from localized macular regions, including rings and Early Treatment of Diabetic Retinopathy Study (ETDRS) sectors. Results: When comparing MSnoON data from all tested areas with respect to the controls, macular GCL+-T and mfPhNR RAD mean values were found to be significantly (ANOVA, p < 0.01) reduced. In the MSonON group, considering both rings and sectors, the GCL+-T values were significantly and linearly correlated (Pearson’s test, p < 0.01) to the mfPhNR RAD values. Conclusions: In MS, even in the absence of optic neuritis, potential primary morpho-functional involvement of the inner macular elements can occur. This impairment widely involves all macular areas and sectors. Full article
(This article belongs to the Section Ophthalmology)
14 pages, 4701 KiB  
Article
A QS21+ CpG-Adjuvanted Rabies Virus G Subunit Vaccine Elicits Superior Humoral and Moderate Cellular Immunity
by Han Cao, Hui Li, Wenzhi Liu, Ning Luan, Jingping Hu, Meijun Kong, Jie Song and Cunbao Liu
Vaccines 2025, 13(8), 887; https://doi.org/10.3390/vaccines13080887 (registering DOI) - 21 Aug 2025
Abstract
Background: Rabies remains a fatal zoonotic disease caused by rabies virus (RABV), posing substantial global health challenges. Current vaccine production faces challenges in manufacturing efficiency and cost-effectiveness. The RABV glycoprotein (RABV-G) serves as the key antigen for eliciting protective immunity. Methods: We developed [...] Read more.
Background: Rabies remains a fatal zoonotic disease caused by rabies virus (RABV), posing substantial global health challenges. Current vaccine production faces challenges in manufacturing efficiency and cost-effectiveness. The RABV glycoprotein (RABV-G) serves as the key antigen for eliciting protective immunity. Methods: We developed a novel QS21+CpG-adjuvanted RABV-G subunit vaccine and systematically compared its performance against three control formulations: mRNA vaccine composed of H270P-targeted mutation packaged in lipid nanoparticles (LNP), named LNP-mRNA-G-H270P, commercial inactivated vaccine, and alum-adjuvanted RABV-G subunit vaccine. Results: The result show that the G+QS21+CpG subunit vaccine elicited superior humoral immunity, as evidenced by significantly higher RABV-G-specific IgG titers and virus-neutralizing antibody responses compared to all other groups. The LNP-mRNA-G-H270P vaccine maintained its expected cellular immunity advantage, with the G+QS21+CpG group exhibiting moderately reduced but still significant levels of IFN-γ-secreting splenocytes and levels of IL-2 in the supernatant of spleen cells, as well as IFN-γ-producing CD4+ T cells. Both LNP-mRNA-G-H270P and G+QS21+CpG vaccine groups provided 100% protection against lethal challenge (50LD50 RABV). Conclusions: These findings provide novel vaccine/adjuvant strategies for rabies while elucidating platform-specific immunogenicity patterns, offering critical insights for pathogens requiring balanced humoral/cellular immunity. Full article
(This article belongs to the Section Vaccine Design, Development, and Delivery)
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20 pages, 3581 KiB  
Article
Long-Term Durability and Variant-Specific Modulation of SARS-CoV-2 Humoral and Cellular Immunity over Two Years
by Lilia Matei, Mihaela Chivu-Economescu, Laura Denisa Dragu, Camelia Grancea, Coralia Bleotu, Raluca Hrișcă, Corneliu Petru Popescu, Carmen C. Diaconu and Simona Maria Ruţă
Int. J. Mol. Sci. 2025, 26(16), 8106; https://doi.org/10.3390/ijms26168106 (registering DOI) - 21 Aug 2025
Abstract
There is an increasing need to understand the long-term dynamics and quality of SARS-CoV-2 immune memory—both humoral and cellular—particularly with emerging variants. This study aimed to evaluate immune durability and variant-specific modulation through a longitudinal analysis of individuals with diverse SARS-CoV-2 exposure histories, [...] Read more.
There is an increasing need to understand the long-term dynamics and quality of SARS-CoV-2 immune memory—both humoral and cellular—particularly with emerging variants. This study aimed to evaluate immune durability and variant-specific modulation through a longitudinal analysis of individuals with diverse SARS-CoV-2 exposure histories, over two years after infection and/or vaccination. The study involved assessing anti-spike IgG and IgA levels over time and analyzing their relationship with neutralizing activity against both ancestral and Omicron SARS-CoV-2 variants. Persistence of T cell responses was evaluated using intracellular cytokine staining (ICS) and activation-induced marker (AIM) assays. Anti-S IgG levels remained stable over time and increased after each immune stimulation, suggesting cumulative immune memory. Neutralizing capacity correlated strongly with IgG levels, showing long-term stability for pre-Omicron variants, but a moderate decline for Omicron. CD4+ and CD8+ T cell responses persisted across all groups, largely unaffected by Omicron mutations. However, cytokine profiles revealed subtle, variant-dependent changes. These findings underscore the durability of cellular immunity and the comparatively reduced robustness of Omicron-specific humoral responses. Such insights are crucial for understanding long-term protection against evolving SARS-CoV-2 variants and guiding public health strategies. Full article
(This article belongs to the Special Issue COVID-19: Molecular Research and Novel Therapy)
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13 pages, 10589 KiB  
Article
Functional Role of miR-138-5p and miR-200b-3p in Testicular Germ Cell Tumors: Molecular Insights into Seminoma and Teratoma Pathogenesis
by Fatemeh Hooshiar, Hossein Azizi, Mahla Masoudi and Thomas Skutella
Int. J. Mol. Sci. 2025, 26(16), 8107; https://doi.org/10.3390/ijms26168107 (registering DOI) - 21 Aug 2025
Abstract
This study aims to investigate the molecular mechanisms underlying germ cell tumors (GCTs), focusing specifically on seminomas and teratomas. By analyzing gene expression profiles and miRNA interactions, the goal is to identify key regulatory miRNAs and signaling pathways that differentiate these tumor types [...] Read more.
This study aims to investigate the molecular mechanisms underlying germ cell tumors (GCTs), focusing specifically on seminomas and teratomas. By analyzing gene expression profiles and miRNA interactions, the goal is to identify key regulatory miRNAs and signaling pathways that differentiate these tumor types and could serve as important regulators for therapy development. Raw data for seminomas and teratomas were extracted from the GEO database, and gene hubs were identified using STRING and Gephi. Signaling pathways and functional annotations were analyzed using miRPathDB, while miRNA–gene interactions were explored via miRWalk. Hub miRNAs were filtered and confirmed using miRDB. This study highlights significant changes in gene expression diversity between tumor and normal gonadal tissues, providing insights into the molecular dynamics of seminomas and teratomas. Distinctions between seminomas and teratomas were identified, shifting the focus toward miRNAs to discover more precise and novel therapeutic approaches. The hub genes of seminomas and teratomas were identified separately. MiRNAs targeting these hub genes were also determined and confirmed. These miRNAs collectively influence essential oncogenic pathways—confirming hsa-miR-138-5p as a regulator of pathways such as Hippo signaling, transcriptional misregulation in cancer, and microRNA cancer signaling in seminomas, and hsa-miR-200b-3p as a regulator of p53 signaling, T cell receptor signaling, and pathways including PI3K/AKT, MAPK/ERK, and Wnt/β-catenin in teratomas—confirming their potential as promising candidates for subtype-specific therapeutic intervention. MiRNAs identified through bioinformatics analyses, and their predicted regulatory roles in key oncogenic pathways, represent potential therapeutic targets or regulators of biological processes. However, further experimental validation is needed to confirm these findings. Full article
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18 pages, 1026 KiB  
Article
Carotenoid Production by Dunaliella salina with Magnetic Field Application
by Izabela Queiroz Silva, Bruno Roswag Machado, Tamires Machado Ferreira, Júlia de Farias Borges, Cláudia Maria Luz Lapa Teixeira and Lucielen Oliveira Santos
Fermentation 2025, 11(8), 487; https://doi.org/10.3390/fermentation11080487 - 21 Aug 2025
Abstract
The use of external triggers in microalgae cultivation has emerged as a promising approach to enhance biomass production and biochemical composition. For instance, magnetic fields (MFs) have had their potential to modulate cellular metabolism and physiological responses explored. This study investigated the effects [...] Read more.
The use of external triggers in microalgae cultivation has emerged as a promising approach to enhance biomass production and biochemical composition. For instance, magnetic fields (MFs) have had their potential to modulate cellular metabolism and physiological responses explored. This study investigated the effects of MF exposure on Dunaliella salina and evaluated its impact on biomass production, pigment synthesis and biochemical composition. The highest biomass concentration (0.59 g L−1) was observed under continuous exposure to 60 mT (MF60-24 h); it represented a 51% increase in comparison with the control. A gradual rise in pH, which reached 10.83, was observed during cultivation. MF exposure also enhanced chlorophyll-a (118%) and carotenoid (95%) concentrations; thus, it improved photosynthetic efficiency and potential oxidative stress responses. The biochemical composition revealed a shift in metabolic pathways after prolonged MF exposure (24 h d−1), decreasing carbohydrate content by 7%, while increasing lipid accumulation by 7%. Scanning electron microscopy (SEM) indicated structural modifications on the cell surface induced by the MF. Therefore, MF applications improve D. salina cultivation and enhance biomass composition for biotechnological applications. Full article
(This article belongs to the Special Issue Cyanobacteria and Eukaryotic Microalgae (2nd Edition))
14 pages, 1799 KiB  
Article
Genotype Frequency of HLA-B*58:01 and Its Association with Paraclinical Characteristics and PSORS1C1 rs9263726 in Gout Patients
by Hien Thu Nguyen, Ha Thi Bui, Yen Thi Thu Hoang, My Ha Hoang, Manh Duc Ngo, Mai Hoang Nguyen, Thuy Thi Thanh Nguyen, Nhuan Tien Ngo and Quang Viet Nguyen
Diagnostics 2025, 15(16), 2114; https://doi.org/10.3390/diagnostics15162114 - 21 Aug 2025
Abstract
Background/Objectives: The HLA-B*58:01 allele is strongly linked to severe cutaneous adverse reactions (SCARs) during allopurinol treatment, and it has been associated with the A allele of PSORS1C1 rs9263726 (G>A). Paraclinical characteristics of gout are indicative of associated comorbid conditions. This study investigated the [...] Read more.
Background/Objectives: The HLA-B*58:01 allele is strongly linked to severe cutaneous adverse reactions (SCARs) during allopurinol treatment, and it has been associated with the A allele of PSORS1C1 rs9263726 (G>A). Paraclinical characteristics of gout are indicative of associated comorbid conditions. This study investigated the genotype frequency of HLA-B*58:01 and its association with paraclinical characteristics and PSORS1C1 rs9263726 in gout patients from Northeast Vietnam. Methods: A total of 133 unrelated gout patients were randomly recruited by the clinician. BioEdit sequence alignment editor version 7.2.5 software (Raleigh, Raleigh, NC, USA) was used for the analysis of nucleotide sequence data of HLA-B gene alleles from the IPD-IMGT/HLA Database, which showed that the HLA-B*58:01 allele can be distinguished from reference and other alleles by specific nucleotide positions: 387C, 379C, 368A, 355A, and 353T (in exon 3); and 319C, 285G, and 209A (in exon 2). HLA-B*58:01 and PSORS1C1 rs9263726 genotypes were identified using Sanger sequencing of PCR products, analyzed with BioEdit software, and verified using the NCBI dbVar database. Statistical analyses were performed using SPSS version 25.0. Results: Our study revealed a significant age difference between male and female gout patients (p < 0.001). Male gout patients had an average age of 51.44 ± 14.59 years, whereas female gout patients were notably older, with an average age of 70.33 ± 10.64 years. Positive correlations were observed between platelet count, serum creatinine, and uric acid levels (r = 0.174, p = 0.045; r = 0.195, p = 0.025) in male gout patients, while only high-density lipoprotein cholesterol showed a statistically significant negative correlation with uric acid levels (r = −0.885, p = 0.002) in female patients. The HLA-B*58:01 allele frequency among study subjects was 6.02%, with 12.03% being heterozygous individuals (*X/HLA-B*58:01, N = 16). The HLA-B*58:01 allele was not detected in female gout patients. White blood cell counts were significantly higher in male gout patients with the *X/HLA-B*58:01genotype compared to those with the *X/*X genotype (p = 0.018). The A allele frequency of PSORS1C1 rs9263726 was 7.89%, and the heterozygous mutant genotype PSORS1C1 GA had a frequency of 15.79% (N = 21). Among the *X/*58:01 carriers, 4.51% had the GG genotype, and 7.52% had the GA genotype at PSORS1C1 rs9263726. Conclusions: Our study showed that the HLA-B*58:01 allele was not detected in female gout patients. White blood cell counts differed significantly between the *X/HLA-B*58:01 and *X/*X groups in male gout patients. The A allele of PSORS1C1 rs9263726 was not consistently associated with HLA-B*58:01 and was not a reliable marker for its detection in this study population. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
27 pages, 12797 KiB  
Article
Adaptive and Pathological Changes of the Cardiac Muscle in a Mouse Model of Renocardiac Syndrome: The Role of Nestin-Positive Cells
by Polina A. Abramicheva, Ilya A. Sokolov, Arina A. Druzhinina, Daria M. Potashnikova, Nadezda V. Andrianova, Dmitry S. Semenovich, Vasily N. Manskikh, Ljubava D. Zorova, Elmira I. Yakupova, Ivan M. Vikhlyantsev, Olga S. Tarasova, Dmitry B. Zorov and Egor Y. Plotnikov
Int. J. Mol. Sci. 2025, 26(16), 8100; https://doi.org/10.3390/ijms26168100 (registering DOI) - 21 Aug 2025
Abstract
Renocardiac syndrome type 4 (RCS4) is a common comorbid pathology, but the mechanisms of kidney dysfunction-induced cardiac remodeling and the involvement of cardiac progenitor cells (CPCs) in this process remain unclear. The aim of this study was to investigate the structural and functional [...] Read more.
Renocardiac syndrome type 4 (RCS4) is a common comorbid pathology, but the mechanisms of kidney dysfunction-induced cardiac remodeling and the involvement of cardiac progenitor cells (CPCs) in this process remain unclear. The aim of this study was to investigate the structural and functional changes in the cardiac muscle in RCS4 induced by unilateral ureteral obstruction (UUO) and the role of nestin+ CPCs in these. Heart function and localization of nestin+ cells in the myocardium were assessed using nestin-GFP transgenic mice subjected to UUO for 14 and 28 days. UUO resulted in cardiac hypertrophy, accompanied by an elongation of the QRS wave on the ECG, decreased expression of Cxcl1, Cxcl9, and Il1b, reduced the number of CD11b+ cells, and increased in titin isoform parameters, such as T1/MHC and TT/MHC ratios, without changes in fibrosis markers. The number of nestin+ cells increased in the myocardium with increased duration of UUO and displayed an SCA-1+TBX5+ phenotype, consistent with CPCs. Thus, cardiac pathology in RCS4 was manifested by cardiomyocyte hypertrophy with changes in the electrophysiological phenotype of the heart, not accompanied by fibrosis or inflammation. Nestin+ cardiac cells retained the CPC phenotype during UUO, and their number increased, which suggests their participation in regenerative processes in the heart. Full article
30 pages, 12865 KiB  
Article
Multi-Omics and Molecular Docking Studies on Caffeine for Its Skin Rejuvenating Potentials
by Peng Shu, Nan Zhao, Qi Zhou, Yuan Wang and Lanyue Zhang
Pharmaceuticals 2025, 18(8), 1239; https://doi.org/10.3390/ph18081239 - 21 Aug 2025
Abstract
Background: Caffeine (CA) exhibits promising reparative effects against UV-induced skin aging, but the specific mechanisms, including differences in gene and metabolite regulation and the involvement of signaling pathways, are still insufficiently elucidated. Methods: This study is on the repairing capability of [...] Read more.
Background: Caffeine (CA) exhibits promising reparative effects against UV-induced skin aging, but the specific mechanisms, including differences in gene and metabolite regulation and the involvement of signaling pathways, are still insufficiently elucidated. Methods: This study is on the repairing capability of CA to ultraviolet (UV)-induced skin aging and explores the ferroptosis pathway through in vitro cell experiments, a UV-aged mouse skin model, and molecular docking. Results: CA enhanced the vitality and proliferation of HaCaT cells, delayed cell aging, reduced reactive oxygen species levels, increased mitochondrial membrane potential, and activated the peroxisome proliferator-activated receptor pathway, as well as repaired UVB-induced cytoskeletal disorders. Simultaneously, CA reduced other related but undesirable biological mechanisms. Moreover, multi-omics and network pharmacology studies suggested that CA mitigated aging by modulating related metabolic and ferroptosis pathways. Additionally, CA effectively reduced lipid peroxidation and intracellular ferrous ion levels and regulated the expression of key ferroptosis proteins, and its potential anti-aging effects were also confirmed through the modulation of ferroptosis pathways. In addition, molecular docking revealed strong interactions between CA and related key proteins, further supporting the potentiality of CA. Conclusions: This study elucidates the effectiveness and potential mechanism of CA to reduce the UV-induced skin aging. Full article
(This article belongs to the Section Pharmacology)
17 pages, 3553 KiB  
Article
Comparative Evaluation of Computational Methods for Validating Housekeeping Gene RT-qPCR Data in 3T3-L1 Cells
by Zhenya Ivanova, Natalia Grigorova, Valeria Petrova, Ekaterina Vachkova and Georgi Beev
Biomedicines 2025, 13(8), 2036; https://doi.org/10.3390/biomedicines13082036 - 21 Aug 2025
Abstract
Background: Postbiotics with anti-adipogenic properties can significantly modify adipocyte metabolism by influencing key cellular pathways involved in lipid accumulation. In preliminary in vitro studies, it is essential to monitor various cellular and subcellular variables, including gene expression and protein synthesis potential, through RT-qPCR [...] Read more.
Background: Postbiotics with anti-adipogenic properties can significantly modify adipocyte metabolism by influencing key cellular pathways involved in lipid accumulation. In preliminary in vitro studies, it is essential to monitor various cellular and subcellular variables, including gene expression and protein synthesis potential, through RT-qPCR analysis. It is also crucial to select internal controls carefully and evaluate their stability for effective normalization and accurate interpretation of the results. Methods: In this study, we assessed the stability of six commonly used housekeeping genes: GAPDH, Actb, HPRT, HMBS, 18S, and 36B4. We analyzed their variability in mature 3T3-L1 adipocytes treated with supernatants from newly isolated Lacticaseibacillus paracasei strains. Our analysis combined classical statistical methods, a ∆Ct analysis, and software algorithms such as geNorm, NormFinder, BestKeeper, and RefFinder. Results: Our stepwise, multiparameter strategy for selecting reference genes led to the exclusion of Actb and 18S as the most variable reference genes. We identified HPRT as the most stable internal control. Additionally, HPRT and HMBS emerged as a stable pair, while the recommended triplet of genes for reliable normalization consists of HPRT, 36B4, and HMBS. Conclusions: The widely used putative genes in similar studies—GAPDH and Actb—did not confirm their presumed stability, which once again emphasizes the need for experimental validation of internal controls to increase the accuracy and reliability of gene expression. Combining a unique biological model—postbiotic-treated adipocytes—with multiple algorithms integrated into a single workflow allows us to provide a methodological template applicable to similar nutritional and metabolic research settings. Full article
(This article belongs to the Section Molecular Genetics and Genetic Diseases)
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42 pages, 3184 KiB  
Review
The β-1,4 GalT-V Interactome—Potential Therapeutic Targets and a Network of Pathways Driving Cancer and Cardiovascular and Inflammatory Diseases
by Subroto Chatterjee, Dhruv Kapila, Priya Dubey, Swathi Pasunooti, Sruthi Tatavarthi, Claire Park and Caitlyn Ramdat
Int. J. Mol. Sci. 2025, 26(16), 8088; https://doi.org/10.3390/ijms26168088 (registering DOI) - 21 Aug 2025
Abstract
UDP-Gal-β-1,4 galactosyltransferase-V (GalT-V) is a member of a large family of galactosyltransferases whose function is to transfer galactose from the nucleotide sugar UDP-galactose to a glycosphingolipid glucosylceramide, to generate lactosylceramide (LacCer). It also causes the N and O glycosylation of proteins in the [...] Read more.
UDP-Gal-β-1,4 galactosyltransferase-V (GalT-V) is a member of a large family of galactosyltransferases whose function is to transfer galactose from the nucleotide sugar UDP-galactose to a glycosphingolipid glucosylceramide, to generate lactosylceramide (LacCer). It also causes the N and O glycosylation of proteins in the Trans Golgi area. LacCer is a bioactive lipid second messenger that activates an “oxidative stress pathway”, leading to critical phenotypes, e.g., cell proliferation, migration angiogenesis, autophagy, and apoptosis. It also activates an “inflammatory pathway” that contributes to the progression of disease pathology. β-1,4-GalT-V gene expression is regulated by the binding of the transcription factor Sp-1, one of the most O-GlcNAcylated nuclear factors. This review elaborates the role of the Sp-1/GalT-V axis in disease phenotypes and therapeutic approaches targeting not only Sp-1 but also Notch-1, Wnt-1 frizzled, hedgehog, and β-catenin. Recent evidence suggests that β-1,4GalT-V may glycosylate Notch-1 and, thus, regulate a VEGF-independent angiogenic pathway, promoting glioma-like stem cell differentiation into endothelial cells, thus contributing to angiogenesis. These findings have significant implications for cancer and cardiovascular disease, as tumor vascularization often resumes aggressively following anti-VEGF therapy. Moreover, LacCer can induce angiogenesis independent of VEGF and its level are reported to be high in tumor tissues. Thus, targeting both VEGF-dependent and VEGF-independent pathways may offer novel therapeutic strategies. This review also presents an up-to-date therapeutic approach targeting the β-1,4-GalT-V interactome. In summary, the β-1,4-GalT-V interactome orchestrates a broad network of signaling pathways essential for maintaining cellular homeostasis. Conversely, its dysregulation can promote unchecked proliferation, angiogenesis, and inflammation, contributing to the initiation and progression of multiple diseases. Environmental factors and smoking can influence β-1,4-GalT-V expression and its interactome, whereas elevated β-1,4-GalT-V expression may serve as a diagnostic biomarker of colorectal cancer, inflammation—exacerbated by factors that may worsen pre-existing cancer malignancies, such as smoking and a Western diet—and atherosclerosis, amplifying disease progression. Increased β-1,4-GalT-V expression is frequently associated with tumor aggressiveness and chronic inflammation, underscoring its potential as both a biomarker and therapeutic target in colorectal and other β-1,4-GalT-V-driven cancers, as well as in cardiovascular and inflammatory diseases. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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26 pages, 1795 KiB  
Article
Effects of Mannan Oligosaccharides on Growth, Antioxidant and Immune Performance, and mTOR Signaling Pathway in Juvenile Tilapia (Oreochromis niloticus)
by Qin Zhang, Luoqing Li, Ziyi Ma, Wenyan He, Enhao Huang, Liuqing Meng, Lan Li, Tong Tong, Huizan Yang, Yongqiang Liu and Haijuan Liu
Animals 2025, 15(16), 2459; https://doi.org/10.3390/ani15162459 - 21 Aug 2025
Abstract
Mannan oligosaccharide (MOS), a prebiotic derived from yeast cell walls, has been shown to enhance growth performance and health status in various aquatic species. As an exogenous antigen adjuvant, MOS modulates T-cell-mediated immune responses, thereby improving immune function and suppressing excessive inflammatory reactions. [...] Read more.
Mannan oligosaccharide (MOS), a prebiotic derived from yeast cell walls, has been shown to enhance growth performance and health status in various aquatic species. As an exogenous antigen adjuvant, MOS modulates T-cell-mediated immune responses, thereby improving immune function and suppressing excessive inflammatory reactions. This study aimed to evaluate the effects of dietary MOS supplementation on growth performance, serum biochemical parameters, muscle composition, digestive enzyme activity, antioxidant and immune status, and the mTOR signaling pathway in juvenile GIFT tilapia (Oreochromis niloticus). Juveniles (initial body weight: 16.17 ± 1.32 g) were randomly assigned to six treatment groups (three replicate tanks per group) and fed diets supplemented with MOS at 0, 0.2%, 0.4%, 0.6%, 0.8%, and 1% (equivalent to 0, 2, 4, 6, 8, and 10 g/kg of diet, respectively) for 60 days. Compared with the control group, fish fed MOS-supplemented diets exhibited significantly higher (p < 0.05) weight gain rates, specific growth rates, and protein efficiency ratios, along with a significantly lower (p < 0.05) feed conversion ratio. Serum albumin, high-density lipoprotein, and lysozyme levels were significantly increased (p < 0.05), whereas triglycerides, low-density lipoprotein, aspartate aminotransferase, and alanine aminotransferase levels were significantly decreased (p < 0.05). In the liver, head kidney, and spleen, the expression of pro-inflammatory genes (tumor necrosis factor α, interleukin 1β, interleukin 6, interleukin 8, and interferon γ) was significantly downregulated (p < 0.05), while the expression of antioxidant and protective genes (superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase, nuclear factor erythroid 2-related factor 2, lysozyme, alkaline phosphatase, interleukin-10, transforming growth factor β, and heat shock protein 70) as well as mTOR signaling pathway-related genes (mammalian target of rapamycin, akt protein kinase B, phosphatidylinositol 3 kinase, and ribosomal protein S6 kinase polypeptide 1) was significantly upregulated (p < 0.05). Overall, MOS positively affects tilapia’s growth, health, and immunity, with 0.60% identified as the optimal dietary level based on growth performance. Full article
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22 pages, 9293 KiB  
Article
Synthesis, Characterization, and In Vitro Cytotoxic Evaluation of Neodymium-Doped Cobalt Ferrite Nanoparticles on Human Cancer Cell Lines
by Slaviţa Rotunjanu, Armand Gogulescu, Narcisa Laura Marangoci, Andrei-Ioan Dascălu, Marius Mioc, Roxana Racoviceanu, Alexandra Mioc, Tamara Maksimović, Oana Eșanu, Gabriela Antal and Codruţa Șoica
Materials 2025, 18(16), 3911; https://doi.org/10.3390/ma18163911 - 21 Aug 2025
Abstract
Cancer is still the world’s most prevalent cause of death, and the limited efficacy of current treatments highlights the requirement for new therapeutic approaches. In this study, neodymium (Nd)-doped cobalt ferrite (CoFe2₋zNdzO4, z = 0; 0.01; 0.02; [...] Read more.
Cancer is still the world’s most prevalent cause of death, and the limited efficacy of current treatments highlights the requirement for new therapeutic approaches. In this study, neodymium (Nd)-doped cobalt ferrite (CoFe2₋zNdzO4, z = 0; 0.01; 0.02; 0.03; 0.05; 0.1) nanoparticles (Nd0-Nd5) were synthesized via the combustion method. The structural, morphological, and magnetic properties were characterized using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), vibrating sample magnetometry (VSM), and scanning transmission electron microscopy (STEM) analysis. The synthesized compounds demonstrated single-phase spinel structures, with morphological differences observed between undoped and Nd-doped samples. The biological activity of the nanoparticles was evaluated on immortalized human keratinocytes (HaCaT) and on cancer cell lines: melanoma (A375), breast adenocarcinoma (MCF-7), and pancreatic carcinoma (PANC-1). The cytotoxic effects of Nd0-Nd5 (50–1000 μg∙mL−1) were assessed through Alamar Blue and lactate dehydrogenase (LDH) release assays. The results indicated a dose-dependent cytotoxic effect in cancer cell lines. Changes in cell morphology, suggesting the induction of the apoptotic processes, were observed through immunofluorescence staining of F-actin and nuclei. These findings highlight the potential of Nd-doped cobalt ferrite nanoparticles as selective anticancer agents, warranting further investigation to fully elucidate their mechanisms of action and therapeutic applicability. Full article
(This article belongs to the Special Issue New Functional Materials for Biomedical Applications)
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15 pages, 1248 KiB  
Article
In Vitro Silencing of MHC-I in Keratinocytes by Herpesvirus US11 Protein to Model Alloreactive Suppression
by Frederik Schlottmann, Sarah Strauß, Peter Maria Vogt and Vesna Bucan
Eur. Burn J. 2025, 6(3), 47; https://doi.org/10.3390/ebj6030047 - 21 Aug 2025
Abstract
Background: Secondary rejection remains a major obstacle in skin allografting. Some viruses, such as human herpesvirus and cytomegalovirus, evade immune detection through proteins like the unique short glycoprotein 11 (US11), which down-regulates major histocompatibility complex (MHC) class I expression. This study explores the [...] Read more.
Background: Secondary rejection remains a major obstacle in skin allografting. Some viruses, such as human herpesvirus and cytomegalovirus, evade immune detection through proteins like the unique short glycoprotein 11 (US11), which down-regulates major histocompatibility complex (MHC) class I expression. This study explores the use of recombinant US11 protein as a biopharmaceutical approach to reduce MHC-I expression and thus decrease alloreactivity in human primary keratinocytes. Methods: Human keratinocytes were treated with recombinant US11 protein, and MHC-I expression was assessed via Western blot and flow cytometry. To evaluate immunomodulatory effects, US11-stimulated keratinocytes were co-cultured with peripheral blood mononuclear cells (PBMCs), and interferon-gamma (IFN-γ) levels were measured by ELISA. Additionally, ex vivo human skin tissue was stimulated with US11 to assess long-term MHC-I modulation. Results: US11 treatment significantly reduced MHC-I surface expression in keratinocytes. Co-cultures showed decreased IFN-γ secretion, indicating lower T cell activation. Human skin tissue stimulated with US11 exhibited reduced MHC-I expression after 7 days. Conclusions: This proof-of-concept study suggests that recombinant US11 protein may serve as an effective biopharmaceutical to reduce keratinocyte immunogenicity. Further in vitro and in vivo studies are warranted to validate its potential for clinical application in skin transplantation. Full article
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12 pages, 821 KiB  
Article
Antiparasitic Effect of Polyphenols and Terpenes from Natural Products Against Trypanosoma cruzi and Leishmania mexicana
by Diana V. Navarrete-Carriola, Gildardo Rivera, Eyra Ortiz-Pérez, Alma D. Paz-González, Ana Verónica Martínez-Vázquez, Laura Victoria Aquino-González, Liliana Argueta-Figueroa, Michael P. Doyle and Adriana Moreno-Rodríguez
Metabolites 2025, 15(8), 560; https://doi.org/10.3390/metabo15080560 - 21 Aug 2025
Abstract
Background: Worldwide, the number of cases of parasitic diseases has been increasing; however, available treatments have variable adverse effects and low efficacy, mainly in Neglected Tropical Diseases such as Chagas disease and Leishmaniasis. Therefore, the development of new and more effective antiparasitic [...] Read more.
Background: Worldwide, the number of cases of parasitic diseases has been increasing; however, available treatments have variable adverse effects and low efficacy, mainly in Neglected Tropical Diseases such as Chagas disease and Leishmaniasis. Therefore, the development of new and more effective antiparasitic drugs is important. Natural products are the source of secondary metabolites with different biological activities, such as antibacterial, anticancer, anti-inflammatory, and antiparasitic. Objectives: In this work, secondary metabolites (phenols and terpenes) from natural products were selected to be evaluated against the epimastigotes of NINOA and A1 strains of Trypanosoma cruzi and the promastigotes of M379 strain and FCQEPS native isolate of Leishmania mexicana. Additionally, their cytotoxicity and selectivity index were determined. Methods: Eighteen secondary metabolites were evaluated in vitro against T. cruzi epimastigotes and L. mexicana promastigotes; additionally, their cytotoxicity on the J774.2 macrophage cell line was determined. Results: The compounds l-(-)-menthol (14, IC50 = 24.52 µM) and β-citronellol (11, IC50 = 21.54 µM) had higher trypanocidal activity than the reference drug (benznidazole) against NINOA and A1 strains of T. cruzi, respectively. On the other hand, para-anisyl alcohol (4, IC50 = 34.89 µM) had higher leishmanicidal activity than the reference drug (glucantime®) against M379 and the FCQEPS native isolate of L. mexicana. Finally, in silico, the determination of their pharmacokinetic and toxicological properties showed that they are promising candidates for oral and topical uses. Conclusions: This study opens the possibility of using secondary metabolites as scaffolds for access to the development of new molecules for the treatment of parasite diseases. Full article
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51 pages, 4873 KiB  
Review
Type 2 Diabetes and the Multifaceted Gut-X Axes
by Hezixian Guo, Liyi Pan, Qiuyi Wu, Linhao Wang, Zongjian Huang, Jie Wang, Li Wang, Xiang Fang, Sashuang Dong, Yanhua Zhu and Zhenlin Liao
Nutrients 2025, 17(16), 2708; https://doi.org/10.3390/nu17162708 - 21 Aug 2025
Abstract
Type 2 diabetes (T2D) is a complex metabolic disease characterized by chronic hyperglycemia due to insulin resistance and inadequate insulin secretion. Beyond the classically implicated organs, emerging evidence highlights the gut as a central player in T2D pathophysiology through its interactions with metabolic [...] Read more.
Type 2 diabetes (T2D) is a complex metabolic disease characterized by chronic hyperglycemia due to insulin resistance and inadequate insulin secretion. Beyond the classically implicated organs, emerging evidence highlights the gut as a central player in T2D pathophysiology through its interactions with metabolic organs. The gut hosts trillions of microbes and enteroendocrine cells that influence inflammation, energy homeostasis, and hormone regulation. Disruptions in gut homeostasis (dysbiosis and increased permeability) have been linked to obesity, insulin resistance, and β-cell dysfunction, suggesting multifaceted “Gut-X axes” contribute to T2D development. We aimed to comprehensively review the evidence for gut-mediated crosstalk with the pancreas, endocrine system, liver, and kidneys in T2D. Key molecular mechanisms (incretins, bile acids, short-chain fatty acids, endotoxins, etc.) were examined to construct an integrated model of how gut-derived signals modulate metabolic and inflammatory pathways across organs. We also discuss clinical implications of targeting Gut-X axes and identify knowledge gaps and future research directions. A literature search (2015–2025) was conducted in PubMed, Scopus, and Web of Science, following PRISMA guidelines (Preferred Reporting Items for Systematic Reviews). Over 150 high-impact publications (original research and review articles from Nature, Cell, Gut, Diabetologia, Lancet Diabetes & Endocrinology, etc.) were screened. Data on gut microbiota, enteroendocrine hormones, inflammatory mediators, and organ-specific outcomes in T2D were extracted. The GRADE framework was used informally to prioritize high-quality evidence (e.g., human trials and meta-analyses) in formulating conclusions. T2D involves perturbations in multiple Gut-X axes. This review first outlines gut homeostasis and T2D pathogenesis, then dissects each axis: (1) Gut–Pancreas Axis: how incretin hormones (GLP-1 and GIP) and microbial metabolites affect insulin/glucagon secretion and β-cell health; (2) Gut–Endocrine Axis: enteroendocrine signals (e.g., PYY and ghrelin) and neural pathways that link the gut with appetite regulation, adipose tissue, and systemic metabolism; (3) Gut–Liver Axis: the role of microbiota-modified bile acids (FXR/TGR5 pathways) and bacterial endotoxins in non-alcoholic fatty liver disease (NAFLD) and hepatic insulin resistance; (4) Gut–Kidney Axis: how gut-derived toxins and nutrient handling intersect with diabetic kidney disease and how incretin-based and SGLT2 inhibitor therapies leverage gut–kidney communication. Shared mechanisms (microbial SCFAs improving insulin sensitivity, LPS driving inflammation via TLR4, and aryl hydrocarbon receptor ligands modulating immunity) are synthesized into a unified model. An integrated understanding of Gut-X axes reveals new opportunities for treating and preventing T2D. Modulating the gut microbiome and its metabolites (through diet, pharmaceuticals, or microbiota therapies) can improve glycemic control and ameliorate complications by simultaneously influencing pancreatic islet function, hepatic metabolism, and systemic inflammation. However, translating these insights into clinical practice requires addressing gaps with robust human studies. This review provides a state-of-the-art synthesis for researchers and clinicians, underlining the gut as a nexus for multi-organ metabolic regulation in T2D and a fertile target for next-generation therapies. Full article
(This article belongs to the Special Issue Dietary Regulation of Glucose and Lipid Metabolism in Diabetes)
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