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18 pages, 2645 KB  
Article
Prolonged 3.5 GHz and 24 GHz RF-EMF Exposure Alters Testicular Immune Balance, Apoptotic Gene Expression, and Sperm Function in Rats
by Syed Muhamad Asyraf Syed Taha, Farah Hanan Fathihah Jaffar, Atikah Hairulazam, Sivasatyan Vijay, Norazurashima Jamaludin, Aini Farzana Zulkifli, Mohd Farisyam Mat Ros, Khairul Osman, Zahriladha Zakaria, Amyrul Azuan Bin Mohd Bahar and Siti Fatimah Ibrahim
Biomedicines 2025, 13(10), 2471; https://doi.org/10.3390/biomedicines13102471 (registering DOI) - 11 Oct 2025
Abstract
 Background/Objectives: The rapid rollout of 5G has renewed interest in potential reproductive effects of mid-band (3.5 GHz) and millimeter-wave (24 GHz) radiofrequency electromagnetic fields (RF-EMF). We examined frequency- and duration-dependent changes in testicular cytokines, apoptosis-related genes, and sperm quality in rats. Methods: [...] Read more.
 Background/Objectives: The rapid rollout of 5G has renewed interest in potential reproductive effects of mid-band (3.5 GHz) and millimeter-wave (24 GHz) radiofrequency electromagnetic fields (RF-EMF). We examined frequency- and duration-dependent changes in testicular cytokines, apoptosis-related genes, and sperm quality in rats. Methods: Male Sprague Dawley rats (n = 6 per group) were exposed for 60 days to 3.5 GHz or 24 GHz RF-EMF for 1 h/day or 7 h/day. The sham controls were housed identically. Testicular expressions of IL-10, IL-6, IL-1β, and TNF-α were quantified; Tp53, Bax, Bcl2, and Casp3 mRNA expressions were measured; and sperm concentration, viability, and motility were evaluated. Results: IL-10 was significantly reduced in the 24 GHz group at both 1-h and 7-h exposure duration. At 7 h, TNF-α was also lower at 24 GHz. Casp3 expression was higher and Tp53 was lower at 3.5 GHz at 1-h exposure duration. Sperm concentration and viability were reduced after 24 GHz exposure at 7 h, while sperm motility was reduced after 3.5 GHz exposure at both durations. Conclusions: Exposure to RF-EMF 3.5 GHz primarily impacts sperm motility via extrinsic pro-apoptotic pathways, while exposure to 24 GHz impacts sperm concentration and viability potentially through immune–apoptotic mechanisms, with all negative effects amplified by 7-h daily exposure.  Full article
(This article belongs to the Special Issue Molecular Regulation of Spermatozoa—Second Edition)
23 pages, 8747 KB  
Article
Dietary Acrylamide Induces Depression via SIRT3-Mediated Mitochondrial Oxidative Injury: Evidence from Multi-Omics and Mendelian Randomization
by Lele Zhang, Shun Li, Shengjie Liu and Zhenjie Wang
Curr. Issues Mol. Biol. 2025, 47(10), 836; https://doi.org/10.3390/cimb47100836 - 10 Oct 2025
Abstract
Acrylamide (ACR), a common dietary pro-oxidant generated in heat-processed foods, disrupts mitochondrial redox homeostasis. While its neurotoxic effects are recognized, the role of ACR in depression remains poorly understood. We hypothesized that dietary ACR exposure promotes depression via SIRT3-dependent mitochondrial oxidative injury. Through [...] Read more.
Acrylamide (ACR), a common dietary pro-oxidant generated in heat-processed foods, disrupts mitochondrial redox homeostasis. While its neurotoxic effects are recognized, the role of ACR in depression remains poorly understood. We hypothesized that dietary ACR exposure promotes depression via SIRT3-dependent mitochondrial oxidative injury. Through an integrative approach combining network toxicology (to prioritize candidate targets), transcriptomics, and Mendelian randomization (MR), we identified SIRT3 as the central mediator. Molecular dynamics simulations demonstrated that ACR’s primary metabolite glycidamide (GA) formed more stable and rigid complexes with key targets (including SIRT3, TP53, CASP3, JUN, PTGS2, and PTK2) than ACR itself, as evidenced by superior structural stability, reduced flexibility, and enhanced hydrogen bonding. Transcriptomic analysis of the human prefrontal cortex (datasets GSE54567 and GSE54568) revealed mitochondrial deacetylase sirtuin 3 (SIRT3) as the most significantly suppressed gene in depression (p < 0.01), suggesting an impairment in Superoxide dismutase 2 (SOD2)-mediated antioxidant defense. MR further established JUN and PTK2 as causal genetic risk factors for depression (JUN: Odds Ratio (OR) = 1.029, 95% CI = 1.002–1.057; PTK2: OR = 1.040, 95% CI = 1.005–1.076; JUN (OR) = 1.048, 95% CI = 1.021–1.076, PTK2: OR = 1.073, 95% CI = 1.039–1.109) of each MR estimates, while other candidates lacked genetic support. Our findings demonstrate that ACR induces depression primarily through SIRT3 suppression, activating JUN/PTK2 pathways, suggesting its potential role in environmental toxicant-induced redox imbalance. Full article
(This article belongs to the Special Issue Feature Papers in Molecular Medicine 2025)
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16 pages, 724 KB  
Article
Does Quality of Life Influence Pro-Environmental Intention? An Extension of Theory of Planned Behaviour
by Suk Min Pang, Hasni Mohd Hanafi, Choy Yoke Chong and Booi Chen Tan
Sustainability 2025, 17(19), 8953; https://doi.org/10.3390/su17198953 - 9 Oct 2025
Abstract
In light of escalating global environmental deterioration, studies on pro-environmental intention and behaviour with the ultimate goal of identifying contributing factors to minimise environmental issues are common. Theory of Planned Behaviour (TPB) is widely used to study environmental intentions and behaviours. However, how [...] Read more.
In light of escalating global environmental deterioration, studies on pro-environmental intention and behaviour with the ultimate goal of identifying contributing factors to minimise environmental issues are common. Theory of Planned Behaviour (TPB) is widely used to study environmental intentions and behaviours. However, how quality of life (QoL) influences these intentions and interactions among TPB’s own variables within a single research framework has not been thoroughly explored. Therefore, this study extends TPB by incorporating the four dimensions of QoL, as measured by the Control, Autonomy, Self-Realisation, and Pleasure (CASP-19) scale, to understand pro-environmental intentions from Malaysian viewpoints. In this study, quantitative approach was applied, and the data were collected from Malaysians aged 18 and above (N = 182) in Klang Valley, Malaysia. Using Partial Least Squares Structural Equation Modelling (PLS-SEM), a two-step approach was employed to assess the measurement and structural models. The findings confirmed Theory of Planned Behaviour (TPB) is a robust model for environmental studies showing that subjective norm and perceived behavioural control significantly influence attitudes toward pro-environmental behaviour, ultimately leading to pro-environmental intention. Interestingly, this study found no relationship between QoL dimensions and pro-environmental intention. Lastly, both theoretical and managerial implications were discussed, and research limitations and suggestions for future research directions were put forward. Full article
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21 pages, 3498 KB  
Article
Effects of Replacing Fishmeal with Soybean Meal on Intestinal Histology, Antioxidation, Endoplasmic Reticulum Stress, Inflammation, Tight Junction, and Microbiota in Olive Flounder (Paralichthys olivaceus)
by Zhenxia Su, Yanjie Zhang, Chaoqing Wei, Fengxiang Zhang, Lei Wang, Yaxuan Li, Zhengqiu Zhang, Jianhe Xu, Zhiguo Dong and Hua Mu
Animals 2025, 15(19), 2895; https://doi.org/10.3390/ani15192895 - 3 Oct 2025
Viewed by 282
Abstract
A limited supply and price shortages of fishmeal with the expansion of aquaculture make it necessary to seek alternative protein sources. Soybean meal (SM) has been the widely preferred replacer for fishmeal in fish diets. Nevertheless, this substitution, especially when given at high [...] Read more.
A limited supply and price shortages of fishmeal with the expansion of aquaculture make it necessary to seek alternative protein sources. Soybean meal (SM) has been the widely preferred replacer for fishmeal in fish diets. Nevertheless, this substitution, especially when given at high doses, potentially shows adverse impact on fish intestinal health. This study aimed to investigate the effect of replacing fishmeal with SM on intestinal health in olive flounder (Paralichthys olivaceus). A 56-day feeding trial was conducted with 450 juvenile fish (initial weight: 6.32 ± 0.01 g) randomly allocated to five diets with graded SM replacement: 0% (FM), 12% (SM12), 24% (SM24), 36% (SM36), and 48% (SM48). The results demonstrated that concentrations of glucose, total triglyceride, and low-density lipoprotein cholesterol increased, whereas total protein and high-density lipoprotein cholesterol contents, and lysozyme activity decreased in serum with increasing dietary SM levels. Meanwhile, total antioxidant capacity and superoxide dismutase activity significantly decreased at replacement levels exceeding 24%, accompanied by elevated malondialdehyde concentration (p < 0.05). Compared with the FM group, the SM24, SM36, and SM48 groups showed significantly reduced VH and increased lamina propria width (p < 0.05). Increasing dietary SM levels upregulated expression of genes related to endoplasmic reticulum stress (ERS) (chop, perk, and grp78), inflammation (tnf-α and il-6), and apoptosis (bax, casp3, casp6, and casp9), while downregulated anti-inflammatory cytokines (il-10 and tgf-β1) and tight junction-related genes (zo-1, zo-2, claudin-5, ocln, muc-13, and muc-15) in the intestine (p < 0.05). There were significant differences in the abundances of intestinal microbiota at both the phylum and genus levels among the FM, SM24, and SM36 groups (p < 0.05), but the clusters and microbiota composition of the SM24 group were more similar to those of the FM group. In conclusion, replacing 24% of fishmeal with SM induced intestinal dysfunction through evoking ERS, inflammation, barrier disruption, and microbial dysbiosis in olive flounder. Full article
(This article belongs to the Section Animal Nutrition)
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12 pages, 558 KB  
Systematic Review
A Systematic Review of Hearing Loss and Its Associated Factors Among Workers in the Metal Industry
by France Selepeng Raphela
J. Otorhinolaryngol. Hear. Balance Med. 2025, 6(2), 18; https://doi.org/10.3390/ohbm6020018 - 1 Oct 2025
Viewed by 309
Abstract
Background/Objectives: Hearing loss is a disorder that develops because of being exposed to high noise levels affecting the quality of life among affected individuals. A review of the literature was conducted to explore the prevalence of hearing loss and its associated factors among [...] Read more.
Background/Objectives: Hearing loss is a disorder that develops because of being exposed to high noise levels affecting the quality of life among affected individuals. A review of the literature was conducted to explore the prevalence of hearing loss and its associated factors among workers in the metal industry. Methods: The literature search was conducted on ScienceDirect, Google Scholar, Pub Med, ResearchGate and African Journals Online databases to identify articles according to the Preferred Reporting Items for Systematic Reviews and Meta analyses (PRISMA) guidelines. The studies published in scientific journals between January 2014 and December 2024 describing hearing loss and its associated factors among workers in the metal industry were considered for inclusion in the review. The articles were screened by the author. The Critical Appraisal Skills Programme (CASP) quality assessment tool with modified checklist questions was used to evaluate the quality of studies. Results: Following the literature search and using the relevant inclusion criteria, a total of 127 articles were identified, and 8 articles with a total of 2605 participants were included in the review. The sample sizes ranged from 93 to 606. The participants’ age ranged from 19 to 65 years. A review of studies showed varying prevalence of hearing loss ranging from 13.8% to 59%. Furthermore, the studies have found working experience, advanced age, cigarette smoking, tinnitus, working in areas of high noise levels and not using hearing protective devices to be associated with a risk of developing hearing loss. Conclusions: The review found that workers in the metal industry are at risk of developing hearing loss and, therefore, implementation of control measures to prevent the occurrence of hearing loss is necessary. Full article
(This article belongs to the Section Otology and Neurotology)
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44 pages, 1809 KB  
Systematic Review
Pain Neuroscience Education in Children and Adolescents with Chronic Pain: A Systematic Review
by Mónica Pico, Carmen Matey-Rodríguez, Ana Domínguez-García, Noemí Yubero and Alejandro Santos-Lozano
Children 2025, 12(10), 1317; https://doi.org/10.3390/children12101317 - 1 Oct 2025
Viewed by 356
Abstract
Background/Objectives: Pain neuroscience education (PNE) has demonstrated efficacy in adults with chronic pain, but the pediatric evidence is still developing, despite its increasingly frequent use. Evidence for the effectiveness of PNE in pediatrics remains fragmented across settings and outcomes, which justifies a systematic [...] Read more.
Background/Objectives: Pain neuroscience education (PNE) has demonstrated efficacy in adults with chronic pain, but the pediatric evidence is still developing, despite its increasingly frequent use. Evidence for the effectiveness of PNE in pediatrics remains fragmented across settings and outcomes, which justifies a systematic evaluation focused on children and adolescents. Methods: Following PRISMA, two reviewers independently screened records (PubMed, Web of Science, PEDro; through 21 July 2025), extracted data, and assessed risk of bias (RoB 2 for randomized controlled trials; NIH/CASP for non-randomized studies). Given the heterogeneity, we conducted a structured narrative synthesis (SWiM) and rated the certainty of evidence with GRADE. PROSPERO: CRD420251062922. Results: Eleven studies met the inclusion criteria. PNE consistently improved pain-related knowledge, with effects maintained at follow-up (moderate certainty); effects on pain intensity, function, and emotional outcomes were small and inconsistent (low certainty), with more favorable patterns when PNE was combined with exercise and/or booster sessions. Digital and gamified formats proved feasible and engaging; parental outcomes showed small improvements where measured. Conclusions: PNE is a promising, low-cost, and scalable component of pediatric chronic pain care, strengthening self-efficacy and adaptive coping. Integration into biopsychosocial, multidisciplinary programs—particularly alongside exercise and family involvement—may optimize outcomes. Larger, standardized trials with long-term follow-up and systematic adverse-event reporting are needed to solidify guidance for clinical practice. Full article
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17 pages, 28862 KB  
Article
LncRNA MEG3 Regulates Glaesserella parasuis-Induced Apoptosis of Porcine Alveolar Macrophages via Regulating ssc-miR-135/CASP8 Axis
by Yongchao Jia, Meiling Qian, Xinlu Sun, Ronglan Yin, Na Li, Aobo Shen, Haoran Wang, Fanhua Zeng, Yuanyuan Zhou and Ronghuan Yin
Microorganisms 2025, 13(10), 2287; https://doi.org/10.3390/microorganisms13102287 - 1 Oct 2025
Viewed by 258
Abstract
Glaesserella parasuis (G. parasuis), a common pathogenic bacterium in the porcine respiratory tract, can cause porcine polyserositis, arthritis, and meningitis. Alveolar macrophages are the first line of defense in the pulmonary innate immunity, and their abnormal apoptosis plays a critical role [...] Read more.
Glaesserella parasuis (G. parasuis), a common pathogenic bacterium in the porcine respiratory tract, can cause porcine polyserositis, arthritis, and meningitis. Alveolar macrophages are the first line of defense in the pulmonary innate immunity, and their abnormal apoptosis plays a critical role in the pathogenic process of G. parasuis. Long non-coding RNA maternally expressed gene 3 (MEG3) is associated with G. parasuis infection, but its mechanism remains incompletely unclear. This study aimed to investigate the role of MEG3 in G. parasuis-induced apoptosis of the porcine alveolar macrophage cell line 3D4/21 and its detailed molecular mechanism. Here, we found that MEG3 overexpression promoted G. parasuis-induced apoptosis and upregulated key extrinsic pathway proteins caspase-8 (CASP8) and caspase-3 (CASP3). Mechanistically, MEG3 functioned as a competing endogenous RNA by sponging ssc-miR-135, which directly targets and inhibits CASP8. Consequently, MEG3 overexpression alleviated ssc-miR-135-mediated repression of CASP8. Functional rescue experiments confirmed that either ssc-miR-135 mimic or CASP8 siRNA reversed the pro-apoptotic effect of MEG3. In conclusion, this study reveals that MEG3 relieves the inhibitory effect of ssc-miR-135 on CASP8 through competitively binding, thereby regulating G. parasuis-induced apoptosis of 3D4/21 cells. This study provides new insights into the pathogenic molecular mechanism of G. parasuis. Full article
(This article belongs to the Section Veterinary Microbiology)
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13 pages, 2497 KB  
Article
Whole-Genome Resequencing Reveals Population Genetic Structure and Selection Signatures in the Golden Wild Yak
by Jianhua Yu, Wei Cong, Xiuming Li, Lu Wang, Kun Jin and Yuguang Zhang
Diversity 2025, 17(10), 687; https://doi.org/10.3390/d17100687 - 30 Sep 2025
Viewed by 293
Abstract
The wild yak (Bos mutus) is a flagship species on the Qinghai–Tibet Plateau, possessing significant ecological functions and conservation value. Using single-nucleotide polymorphism markers from whole-genome resequencing, we systematically analyzed golden wild yak (n = 37), common wild yak ( [...] Read more.
The wild yak (Bos mutus) is a flagship species on the Qinghai–Tibet Plateau, possessing significant ecological functions and conservation value. Using single-nucleotide polymorphism markers from whole-genome resequencing, we systematically analyzed golden wild yak (n = 37), common wild yak (n = 106), and domestic yak (Bos grunniens) (n = 20) to characterize the population genetic structure and adaptive selection signals in the golden wild yak. Genetic diversity analyses revealed that the golden wild yak had the lowest nucleotide diversity (π = 0.00148) and the highest inbreeding coefficient (FHom = 0.043). Population structure analyses integrating principal component analysis, phylogenetic tree, and ancestral component clustering indicated that the golden wild yak formed a relatively independent evolutionary lineage. However, its genetic differentiation from sympatric common wild yak population was limited (fixation index = 0.031). Selective sweep analysis identified a set of candidate positively selected genes in the golden wild yak genome associated with key traits and physiological functions, including coat color (TYRP1), hypoxia adaptation (MYH11, POLQ), reproductive function (SLC9C1, SPAG16, CFAP97D1), and immune response (CASP8, PGGT1B, BIRC6). Overall, our study reveals a distinct genetic background and selection signatures in the golden wild yak and provides genomic insights to inform the conservation and management of the wild yak. Full article
(This article belongs to the Special Issue Bison and Beyond: Achievements and Problems in Wildlife Conservation)
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18 pages, 4007 KB  
Article
Synergistic Corrosion Inhibition of Mild Steel in Acidic Media by a Benzimidazole–Thiophene Ligand and Its Metal Complexes: A Multi-Technique Electrochemical Approach
by Mariya Kadiri, Majid Driouch, Ibissam Elaaraj, Ayoub Tanji, Afafe Elabbadi, Mohammed Fahim, Mouhcine Sfaira and Hendra Hermawan
Materials 2025, 18(19), 4545; https://doi.org/10.3390/ma18194545 - 30 Sep 2025
Viewed by 356
Abstract
This study investigates the corrosion inhibition efficiency of [2-(thiophen-2-yl)-1-(thiophen-2-ylmethyl)-1H-benzo[d]imidazole] and its Zn and Cu complexes for mild steel in 1.0 M HCl. The ligand was selected for its non-toxic profile and high electron density, favoring strong adsorption onto the metal surface. Electrochemical methods, [...] Read more.
This study investigates the corrosion inhibition efficiency of [2-(thiophen-2-yl)-1-(thiophen-2-ylmethyl)-1H-benzo[d]imidazole] and its Zn and Cu complexes for mild steel in 1.0 M HCl. The ligand was selected for its non-toxic profile and high electron density, favoring strong adsorption onto the metal surface. Electrochemical methods, including EIS, PDP, LPR, and CASP, were employed to evaluate the inhibitors’ performance. The results showed a significant decrease in corrosion current density and increased polarization resistance, with the Zn complex achieving the highest inhibition efficiency (93.8%). EIS fitting confirmed the formation of a protective film with high charge transfer and film resistance. Surface analyses by SEM and EDS revealed smoother steel morphology and inhibitor adsorption. XPS confirmed the presence of Fe3+, Zn2+and Cu2+ oxides, as well as all active inhibitor elements on the surface, supporting a mixed inhibition mechanism. The enhanced performance of the metal complexes is attributed to synergistic effects between the metal ions and the heterocyclic ligand, offering a promising strategy for the design of effective and environmentally friendly corrosion inhibitors. Full article
(This article belongs to the Special Issue Advances in Corrosion and Protection of Metallic Materials)
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21 pages, 3542 KB  
Systematic Review
Comparison of Different Treatment Outcomes for Refractory Overactive Bladder: A Systematic Review and Meta-Analysis
by Maria Patricia Roman, Răzvan Ciortea, Stergios K. Doumouchtsis, Andrei Mihai Măluțan, Carmen Elena Bucuri, Cristina Mihaela Ormindean, Viorela Elena Suciu, Ionel Daniel Nati, Andreea Căilean and Dan Mihu
Toxins 2025, 17(10), 479; https://doi.org/10.3390/toxins17100479 - 26 Sep 2025
Viewed by 617
Abstract
Background: Refractory overactive bladder (OAB) poses a significant clinical burden, often severely impacting quality of life (QoL). While intradetrusor onabotulinumtoxinA (BoNT-A) and sacral neuromodulation (SNM) are established therapeutic options, a direct comparison of their efficacy and safety profiles is essential to guide clinical [...] Read more.
Background: Refractory overactive bladder (OAB) poses a significant clinical burden, often severely impacting quality of life (QoL). While intradetrusor onabotulinumtoxinA (BoNT-A) and sacral neuromodulation (SNM) are established therapeutic options, a direct comparison of their efficacy and safety profiles is essential to guide clinical decision-making. This study compares BoNT-A against placebo and SNM for the management of refractory OAB in women. Methods: Following PRISMA guidelines, PubMed, Scopus, CENTRAL, and Google Scholar were searched until February 2025 for randomized controlled trials (RCTs) and cohort studies on treatment alternatives for refractory OAB. Treatment outcomes at 3- (BoNT-A vs. placebo) and 6-month (BoNT-A vs. SNM) follow-up were analyzed. Odds ratios (ORs) and mean differences (MDs) were calculated for dichotomous and continuous variables, respectively, with heterogeneity assessed via I2 test. Study quality was evaluated using CASP tools. Results: Pooled data from 12 studies (2645 patients) indicated that BoNT-A significantly reduced urgency urinary incontinence (UUI) episodes compared to placebo (p = 0.02) and SNM (p = 0.0008). Additionally, a ≥75% reduction in UUI episodes was more likely with BoNT-A compared to both placebo (p < 0.00001) and SNM (p < 0.00001). Complete resolution of UUI was more likely with BoNT-A compared to placebo (p < 0.00001); however, when compared to SNM, the latter demonstrated a higher rate of complete UUI resolution (p < 0.00001). Patient-reported QoL did not show significant differences between BoNT-A and SNM (p = 0.2). Urinary tract infection (UTI) risk was higher with BoNT-A than both comparators. Conclusions: While BoNT-A offers robust symptom control, its safety profile necessitates careful patient selection. SNM remains a viable alternative for those prioritizing fewer adverse events. The study highlights the need for standardized outcome reporting, long-term cost-effectiveness analyses, and personalized treatment approaches. Full article
(This article belongs to the Section Bacterial Toxins)
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23 pages, 12833 KB  
Article
Enteromorpha prolifera Polysaccharides Alleviate Valproic Acid-Induced Neuronal Apoptosis in a Cellular Model of Autism Spectrum Disorder
by Xulan Zhou, Hui Su, Jiaxuan Chen, Li Liu, Qian Zhou, Xiaochun Xia and Juan Wang
Curr. Issues Mol. Biol. 2025, 47(10), 796; https://doi.org/10.3390/cimb47100796 - 25 Sep 2025
Viewed by 289
Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental condition marked by social/communication deficits and behavioral abnormalities, with neuronal apoptosis and immune-inflammatory dysregulation implicated in its pathogenesis. Marine-derived polysaccharides, particularly those from Enteromorpha prolifera (PEPs), exhibit neuroprotective and anti-inflammatory properties—yet their therapeutic potential for ASD [...] Read more.
Autism spectrum disorder (ASD) is a neurodevelopmental condition marked by social/communication deficits and behavioral abnormalities, with neuronal apoptosis and immune-inflammatory dysregulation implicated in its pathogenesis. Marine-derived polysaccharides, particularly those from Enteromorpha prolifera (PEPs), exhibit neuroprotective and anti-inflammatory properties—yet their therapeutic potential for ASD remains unexplored. Major monosaccharide components of PEPs were identified as rhamnose, xylose, glucose, glucuronic acid, galactose, and ribose through ion chromatography analysis. Infrared spectroscopy confirmed PEPs as pyranose-type polysaccharides with α-glycosidic bonds and uronic acids, while gel permeation chromatography showed a predominant molecular weight of 3.813 kDa (83.919%). To explore the therapeutic potential of PEPs in ASD, a comprehensive method combining network pharmacology, molecular docking, and in vitro validation was conducted. A total of 235 ASD-related target proteins were predicted, with enrichment analyses indicating significant involvement in pathways such as neuroactive ligand–receptor interaction and the MAPK signaling pathway. In vitro assays using valproic acid (VPA)-induced HT22 neuronal cells showed that PEPs significantly attenuated apoptosis. Western blot analysis further confirmed the downregulation of HSP90AA1, cleaved CASP3/pro-CASP3, p-NF-κB1/NF-κB1, p-AKT1/AKT, and p-mTOR/mTOR, as well as the upregulation of IκBα after PEPs treatment. These findings suggest that PEPs exert neuroprotective effects through the modulation of apoptosis and inflammation-related signaling pathways, supporting their potential as a promising candidate for further study in ASD. Full article
(This article belongs to the Section Molecular Medicine)
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13 pages, 4016 KB  
Article
Proteomic Profiling of Limited-Stage Follicular Lymphoma Reveals Differentially Expressed Proteins Linked to Disease Progression Post-Radiation Therapy
by Jonas Klejs Hemmingsen, Marie Hairing Enemark, Emma Frasez Sørensen, Cecilie Dohrmann, Kristina Lystlund Lauridsen, Stephen Jacques Hamilton-Dutoit, Robert Kridel, Bent Honoré and Maja Ludvigsen
Int. J. Mol. Sci. 2025, 26(19), 9306; https://doi.org/10.3390/ijms26199306 - 23 Sep 2025
Viewed by 354
Abstract
Follicular lymphoma (FL) is the most common indolent lymphoma. Despite a generally favorable prognosis and long-term survival for many patients, FL remains incurable, with disease progression occurring in approximately half of limited-stage FL cases. In this study, we employed high-throughput mass spectrometry-based proteomics [...] Read more.
Follicular lymphoma (FL) is the most common indolent lymphoma. Despite a generally favorable prognosis and long-term survival for many patients, FL remains incurable, with disease progression occurring in approximately half of limited-stage FL cases. In this study, we employed high-throughput mass spectrometry-based proteomics to explore the differential protein expression in diagnostic lymphoma biopsies from 26 limited-stage FL patients. Of these, 9 patients experienced subsequent disease progression (sp-FL), while 17 did not (np-FL). A total of 1940 proteins were identified, with 78 showing significant differential expression between progressing and non-progressing cases. Unsupervised clustering analyses were able to separate the two patient groups based on these differential protein profiles. Notably, proteins involved in metabolism, immune regulation, and apoptosis were downregulated in sp-FL samples. Among the identified proteins, caspase 4 and 8 (CASP4 and CASP8) were further evaluated. The low expression of CASP4 in the diagnostic lymphoma tissue correlated with shorter progression-free survival (PFS) (p < 0.001), primarily with this difference apparent in the expression profiles in the intrafollicular areas (p = 0.015). Similarly, low CASP8 expression was associated with inferior PFS (p = 0.031). Interestingly, addressing the expression pattern for advanced-stage FL patients, the low protein expression of both CASP4 and CASP8 was also found to be associated with progressing cases, suggesting their potential role in disease pathogenesis independent of the disease stage. With further research, the expression pattern of CASP4 and CASP8 may enable the early prediction of disease progression in FL patients, which may ultimately improve patient stratification and allow for more individualized treatment strategies. Full article
(This article belongs to the Special Issue Role of Proteomics in Human Diseases and Infections)
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14 pages, 1427 KB  
Article
Modulation of Detoxification, Immune, and Epigenetic Systems by Two Aryl Organophosphorus Flame Retardants During Early Development in Zebrafish
by Montserrat Solé, Sílvia Joly, Sergi Omedes, Isabel Forner-Piquer and Laia Ribas
Toxics 2025, 13(9), 794; https://doi.org/10.3390/toxics13090794 - 18 Sep 2025
Viewed by 463
Abstract
Organophosphorus flame retardants (OPFRs) are emerging alternatives to halogenated compounds, yet their environmental toxicity remains underexplored. This study evaluated the developmental toxicity of two aryl-OPFRs, triphenyl phosphate (TPP) and tricresyl phosphate (TCP), in zebrafish (Danio rerio) from 2 h to 5 [...] Read more.
Organophosphorus flame retardants (OPFRs) are emerging alternatives to halogenated compounds, yet their environmental toxicity remains underexplored. This study evaluated the developmental toxicity of two aryl-OPFRs, triphenyl phosphate (TPP) and tricresyl phosphate (TCP), in zebrafish (Danio rerio) from 2 h to 5 days post fertilization (hpf–dpf). Survival, hatching rate, and malformations were assessed across concentrations of 250–1000 µg/L, alongside with gene expression analysis at 5 dpf (250 and 500 µg/L) targeting detoxification (ces2), immune responses (il1β, casp9), and epigenetic markers (dnmt1, dnmt3). In vitro enzymatic assays evaluated interactions of both aryl-OPFRs with carboxylesterase (CE) and acetylcholinesterase (AChE) enzymes. While no significant morphological effects were observed, TPP showed higher toxicity than TCP. Notably, TCP (500 µg/L) downregulated genes linked to metabolism and immunity. CE activity and ces2 modulation may suggest CE as a potential biomarker for aryl-OPFR exposure. These findings, although at concentrations above the environmental ones, may be valuable for mechanistic purposes and underscore the need for further investigation in developmental toxicity given their lipophilic nature and distinct molecular responses. Full article
(This article belongs to the Special Issue Hazardous Pollutants in Marine Ecosystems)
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18 pages, 3287 KB  
Article
In Silico and In Vitro Studies of Anti-Inflammatory, Anti-Oxidative Stress, and Anti-Apoptosis Effect of 7-Octenoic Acid Derived from Moringa oleifera Lam., on LPS-Induced Monocyte-Derived Macrophages (MDM)
by Kittipong Srimuang, Watunyoo Buakaew, Yordhathai Thongsri, Krai Daowtak, Pachuen Potup, Antonio Ferrante and Kanchana Usuwanthim
Int. J. Mol. Sci. 2025, 26(18), 8911; https://doi.org/10.3390/ijms26188911 - 12 Sep 2025
Viewed by 912
Abstract
While Moringa oleifera Lam. (MO) extracts are known to have various bioactive properties, including anti-inflammatory properties, the components responsible still remain to be identified. This study explores the protective effects of the MO component, 7-octenoic acid (7OCT) in LPS-stimulated THP-1 macrophage inflammatory responses. [...] Read more.
While Moringa oleifera Lam. (MO) extracts are known to have various bioactive properties, including anti-inflammatory properties, the components responsible still remain to be identified. This study explores the protective effects of the MO component, 7-octenoic acid (7OCT) in LPS-stimulated THP-1 macrophage inflammatory responses. The compound significantly downregulated the production of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, as well as the expression of inflammation-related genes NFKB1, PTGS2, and NOS2. Additionally, it inhibited the nuclear translocation of NF-κB p65, a key transcription factor of inflammatory signaling cascade. Effects on oxidative stress showed that 7OCT inhibited LPS-induced NADPH oxidase 2 (NOX2) component genes including CYBB, CYBA, NCF1, NCF2, and NFE2L2, along with phosphorylated NOX2 and p47phox proteins. The compound reduced the expression of TP53, BAX, CASP3, and CASP7, while enhancing BCL2 expression and Bcl-2 protein levels, suggesting an effect on apoptosis. Decreased levels of BAX, caspase-3, and cleaved caspase-3 proteins further confirmed its anti-apoptotic effect. Our findings suggest that 7OCT exhibits strong anti-inflammatory, antioxidant, and anti-apoptotic properties. Full article
(This article belongs to the Topic Oxidative Stress and Inflammation, 3rd Edition)
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Article
Development of a Comprehensive Lesion Severity Classification Model for Largemouth Bass (Micropterus salmoides) Ranavirus (LMBV) Based on Machine Vision
by Hui Sun, Jixiang Hua, Yifan Tao, Ziying Yang, Taide Zhu, Siqi Lu, Wen Wang, Yalun Dong, Linbing Zhang, Jixiang He, Jie He and Jun Qiang
Int. J. Mol. Sci. 2025, 26(18), 8810; https://doi.org/10.3390/ijms26188810 - 10 Sep 2025
Viewed by 308
Abstract
This study presents the development of a quantitative evaluation method utilizing machine vision technology to characterize the extent of body surface damage in largemouth bass (Micropterus salmoides) infected with largemouth bass ranavirus (LMBV). High-resolution, multi-angle images (6000 × 4000 pixels) of [...] Read more.
This study presents the development of a quantitative evaluation method utilizing machine vision technology to characterize the extent of body surface damage in largemouth bass (Micropterus salmoides) infected with largemouth bass ranavirus (LMBV). High-resolution, multi-angle images (6000 × 4000 pixels) of the body surface from 239 infected specimens were acquired at a fixed distance of 40 cm using a SONY ILCE-7RM3 digital camera within a GODOX-LST60 softbox. Key parameters, including the number of segmented injury areas, the count of body surface lesions, and the total lesion area, were analyzed. These parameters were integrated through principal component analysis (PCA) to construct a comprehensive damage scoring model. The severity of viral-induced body surface damage was categorized into four grades: uninjured (0), minor injury (1), moderate injury (2), and severe injury (3). Histopathological examination revealed that early-stage infection (grade 1) predominantly exhibited localized hemorrhagic spots in the muscular region of the body side (B/E region) with limited lesion area. In contrast, moderate to severe infections (grades 2–3) were characterized by extensive ulceration, muscle necrosis, and visceral lesions, including hepatic fibrosis and splenic granulomatous formations. Quantitative real-time PCR (qRT-PCR) analysis demonstrated a progressive upregulation of pro-inflammatory cytokines (IL-6, IL-8, TNF-α, CXCL2) in immune organs, concomitant with increased expression of apoptosis-related genes (CASP8, CYC). This study successfully established a rapid and objective quantitative grading system for ranavirus infection, offering a novel technical approach for early diagnosis and precise prevention and control strategies against largemouth bass ranavirus. Full article
(This article belongs to the Section Molecular Biology)
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