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16 pages, 3103 KiB  
Article
Resin Composites with Anti-Biofouling Zwitterionic Polymer and Silica/Zirconia Filler for Digital Light Processing (DLP) of Dental Protheses
by Yun-Hee Lee, Jae-Min Jung, Gyu-Nam Kim and Young-Hag Koh
Materials 2025, 18(15), 3677; https://doi.org/10.3390/ma18153677 - 5 Aug 2025
Abstract
This study aimed to develop an innovative resin composite with anti-biofouling properties, tailored to prosthesis fabrication in dentistry using a digital light processing (DLP) 3D-printing technique. The resin composite was formulated using a blend of dental monomers, with the integration of 2-methacryloyloxylethyl phosphorylcholine [...] Read more.
This study aimed to develop an innovative resin composite with anti-biofouling properties, tailored to prosthesis fabrication in dentistry using a digital light processing (DLP) 3D-printing technique. The resin composite was formulated using a blend of dental monomers, with the integration of 2-methacryloyloxylethyl phosphorylcholine (MPC) with anti-biofouling behavior and γ-MPS-treated silica-zirconia powder for simultaneous mechanical reinforcement. The overall characterization of the resin composite was carried out using various contents of MPC incorporated into the resin (0–7 wt%) for examining the rheological behavior, photopolymerization, flexural strength/modulus, microstructure and anti-biofouling efficiency. The resin composite demonstrated a significant reduction in bacterial adhesion (97.4% for E. coli and 86.5% for S. aureus) and protein adsorption (reduced OD value from 1.3 ± 0.4 to 0.8 ± 0.2) with 7 wt% of MPC incorporation, without interfering with photopolymerization to demonstrate potential suitability for 3D printing without issues (p < 0.01, and p < 0.05, respectively). The incorporation and optimization of γ-MPS-treated silica-zirconia powder (10–40 vol%) enhanced mechanical properties, leading to a reasonable flexural strength (103.4 ± 6.1 MPa) and a flexural modulus (4.3 ± 0.4 GPa) at 30 vol% (n = 6). However, a further increase to 40 vol% resulted in a reduction in flexural strength and modulus; nevertheless, the results were above ISO 10477 standards for dental materials. Full article
(This article belongs to the Special Issue Innovative Restorative Dental Materials and Fabrication Techniques)
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21 pages, 896 KiB  
Article
Insights into FGFR4 (rs351855 and rs7708357) Gene Variants, Ki-67 and p53 in Pituitary Adenoma Pathophysiology
by Martyna Juskiene, Monika Duseikaite, Alvita Vilkeviciute, Egle Kariniauske, Ieva Baikstiene, Jurgita Makstiene, Lina Poskiene, Arimantas Tamasauskas, Rasa Liutkeviciene, Rasa Verkauskiene and Birute Zilaitiene
Int. J. Mol. Sci. 2025, 26(15), 7565; https://doi.org/10.3390/ijms26157565 (registering DOI) - 5 Aug 2025
Abstract
To determine the association between FGFR4 (rs351855 and rs7708357) gene variants, serum levels, and immunohistochemical markers (Ki-67 and p53) in pituitary adenoma (PA), a case-control study was conducted involving 300 subjects divided into two groups: the control group (n = 200) and [...] Read more.
To determine the association between FGFR4 (rs351855 and rs7708357) gene variants, serum levels, and immunohistochemical markers (Ki-67 and p53) in pituitary adenoma (PA), a case-control study was conducted involving 300 subjects divided into two groups: the control group (n = 200) and a group of PA (n = 100). The genotyping of FGFR4 rs351855 and rs7708357 was carried out using the real-time polymerase chain reaction (RT-PCR) method. The serum FGFR4 levels were measured using the ELISA method. Immunohistochemical analysis (Ki-67 and p53) was conducted. Statistical analysis of the data was performed using IBM SPSS Statistics 30.0 software. There were no statistically significant differences after analyzing the genotypes and alleles of FGFR4 rs351855 and rs7708357 in patients with PA and control groups (all p > 0.05). After evaluating the distribution of genotypes and alleles of FGFR4 rs351855 and rs7708357 in micro/macro, invasiveness, activity, and recurrence of PA and the control groups, the analysis showed no statistically significant differences between the groups (p > 0.05). Similarly, no significant differences in FGFR4 levels were observed between PA patients and control group (median (IQR): 3642.41 (1755.08) pg/mL vs. 3126.24 (1334.15) pg/mL, p = 0.121). Immunohistochemistry for Ki-67 revealed a labeling index (LI) of <1% in 25.5% of patients with PA, an LI of 1% in 10.9%, and an LI of >1% in 63.6% of patients. Further analyses showed no statistically significant associations with tumor size, invasiveness, activity, or recurrence. Immunohistochemistry for p53 revealed that macroadenomas had a significantly higher p53 H-score compared to microadenomas (median (IQR): 30.33 (28.68) vs. 18.34 (17.65), p = 0.005). Additionally, a moderate, statistically significant positive correlation between the Ki-67 LI and the p53 expression was found (Spearman’s ρ = 0.443, p = 0.003, n = 43). FGFR4 variants and serum protein levels were not significantly associated with PA risk or tumor features. Conversely, immunohistochemical markers Ki-67 and p53 were more informative, with higher p53 expression in macroadenomas and a moderate positive correlation between Ki-67 and p53, highlighting their potential relevance in tumor growth assessment. Full article
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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18 pages, 5256 KiB  
Article
Impact of Alginate Oligosaccharides on Ovarian Performance and the Gut Microbial Community in Mice with D-Galactose-Induced Premature Ovarian Insufficiency
by Yan Zhang, Hongda Pan, Dao Xiang, Hexuan Qu and Shuang Liang
Antioxidants 2025, 14(8), 962; https://doi.org/10.3390/antiox14080962 (registering DOI) - 5 Aug 2025
Abstract
Premature ovarian insufficiency (POI) is an important factor in female infertility and is often associated with oxidative stress. Alginate oligosaccharides (AOSs), derived from the degradation of alginate, have been demonstrated to have protective effects against various oxidative stress-related diseases. However, the impact of [...] Read more.
Premature ovarian insufficiency (POI) is an important factor in female infertility and is often associated with oxidative stress. Alginate oligosaccharides (AOSs), derived from the degradation of alginate, have been demonstrated to have protective effects against various oxidative stress-related diseases. However, the impact of AOSs on POI has not been previously explored. The current study explored the effects of AOSs on ovarian dysfunction in a mouse model of POI induced by D-galactose (D-gal). Female C57BL/6 mice were randomly divided into five groups: the control (CON), POI model (D-gal), and low-, medium-, and high-dose AOS groups (AOS-L, 100 mg/kg/day; AOS-M, 150 mg/kg/day; AOS-H, 200 mg/kg/day). For 42 consecutive days, mice in the D-gal, AOS-L, AOS-M, and AOS-H groups received daily intraperitoneal injections of D-gal (200 mg/kg/day), whereas those in the CON group received equivalent volumes of sterile saline. Following D-gal injection, AOSs were administered via gavage at the specified doses; mice in the CON and D-gal groups received sterile saline instead. AOS treatment markedly improved estrous cycle irregularities, normalized serum hormone levels, reduced granulosa cell apoptosis, and increased follicle counts in POI mice. Moreover, AOSs significantly reduced ovarian oxidative stress and senescence in POI mice, as indicated by lower levels of malondialdehyde (MDA), higher activities of catalase (CAT) and superoxide dismutase (SOD), and decreased protein expression of 4-hydroxynonenal (4-HNE), nitrotyrosine (NTY), 8-hydroxydeoxyguanosine (8-OHdG), and p16 in ovarian tissue. Analysis of the gut microbiota through 16S rRNA gene sequencing and short-chain fatty acid (SCFA) analysis revealed significant differences in gut microbiota composition and SCFA levels (acetic acid and total SCFAs) between control and D-gal-induced POI mice. These differences were largely alleviated by AOS treatment. AOSs changed the gut microbiota by increasing the abundance of Ligilactobacillus and decreasing the abundance of Clostridiales, Clostridiaceae, Marinifilaceae, and Clostridium_T. Additionally, AOSs mitigated the decline in acetic acid and total SCFA levels observed in POI mice. Notably, the total SCFA level was significantly correlated with the abundance of Ligilactobacillus, Marinifilaceae, and Clostridium_T. In conclusion, AOS intervention effectively mitigates ovarian oxidative stress, restores gut microbiota homeostasis, and regulates the microbiota–SCFA axis, collectively improving D-gal-induced POI. Therefore, AOSs represent a promising therapeutic strategy for POI management. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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18 pages, 3940 KiB  
Article
CTCF Represses CIB2 to Balance Proliferation and Differentiation of Goat Myogenic Satellite Cells via Integrin α7β1–PI3K/AKT Axis
by Changliang Gong, Huihui Song, Zhuohang Hao, Zhengyi Zhang, Nanjian Luo and Xiaochuan Chen
Cells 2025, 14(15), 1199; https://doi.org/10.3390/cells14151199 - 5 Aug 2025
Abstract
Skeletal muscle development is a critical economic trait in livestock, governed by myogenic satellite cell regulation. Integrins mediate mechanical anchorage to the ECM and enable ECM–intracellular signaling. CIB2, as an EF-hand-domain protein involved in mechanotransduction, shows significant developmental regulation in goat muscle. [...] Read more.
Skeletal muscle development is a critical economic trait in livestock, governed by myogenic satellite cell regulation. Integrins mediate mechanical anchorage to the ECM and enable ECM–intracellular signaling. CIB2, as an EF-hand-domain protein involved in mechanotransduction, shows significant developmental regulation in goat muscle. Although the role of CIB2 in skeletal muscle growth is poorly characterized, we observed pronounced developmental upregulation of IB2 in postnatal goat muscle. CIB2 expression increased >20-fold by postnatal day 90 (P90) compared to P1, sustaining elevation through P180 (p < 0.05). Functional investigations indicated that siRNA-mediated knockdown of CIB2 could inhibit myoblast proliferation by inducing S-phase arrest (p < 0.05) and downregulating the expression of CDK4/Cyclin D/E. Simultaneously, CIB2 interference treatment was found to decrease the proliferative activity of goat myogenic satellite cells, yet it significantly promoted differentiation by upregulating the expression of MyoD/MyoG/MyHC (p < 0.01). Mechanistically, CTCF was identified as a transcriptional repressor binding to an intragenic region of the CIB2 gene locus (ChIP enrichment: 2.3-fold, p < 0.05). Knockdown of CTCF induced upregulation of CIB2 (p < 0.05). RNA-seq analysis established CIB2 as a calcium signaling hub: its interference activated IL-17/TNF and complement cascades, while overexpression suppressed focal adhesion/ECM–receptor interactions and enriched neuroendocrine pathways. Collectively, this study identifies the CTCF-CIB2–integrin α7β1–PI3K/AKT axis as a novel molecular mechanism that regulates the balance of myogenic fate in goats. These findings offer promising targets for genomic selection and precision breeding strategies aimed at enhancing muscle productivity in ruminants. Full article
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16 pages, 4427 KiB  
Article
Garlic-Derived Allicin Attenuates Parkinson’s Disease via PKA/p-CREB/BDNF/DAT Pathway Activation and Apoptotic Inhibition
by Wanchen Zeng, Yingkai Wang, Yang Liu, Xiaomin Liu and Zhongquan Qi
Molecules 2025, 30(15), 3265; https://doi.org/10.3390/molecules30153265 - 4 Aug 2025
Abstract
Allicin (ALC), a naturally occurring organosulfur compound derived from garlic (Allium sativum), exhibits potential neuroprotective properties. Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by degeneration of dopaminergic neurons and motor dysfunction. This study utilized bioinformatics and network pharmacology methods [...] Read more.
Allicin (ALC), a naturally occurring organosulfur compound derived from garlic (Allium sativum), exhibits potential neuroprotective properties. Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by degeneration of dopaminergic neurons and motor dysfunction. This study utilized bioinformatics and network pharmacology methods to predict the anti-PD mechanism of ALC and established in vivo and in vitro PD models using 6-hydroxydopamine (6-OHDA) for experimental verification. Network pharmacological analysis indicates that apoptosis regulation and the PKA/p-CREB/BDNF signaling pathway are closely related to the anti-PD effect of ALC, and protein kinase A (PKA) and dopamine transporter (DAT) are key molecular targets. The experimental results show that ALC administration can alleviate the cytotoxicity of SH-SY5Y induced by 6-OHDA and simultaneously improve the motor dysfunction and dopaminergic neuron loss in PD mice. In addition, ALC can also activate the PKA/p-CREB/BDNF signaling pathway and increase the DAT level in brain tissue, regulate the expression of BAX and Bcl-2, and reduce neuronal apoptosis. These results indicate that ALC can exert anti-PD effects by up-regulating the PKA/p-CREB/BDNF/DAT signaling pathway and inhibiting neuronal apoptosis, providing theoretical support for the application of ALC in PD. Full article
(This article belongs to the Topic Natural Products and Drug Discovery—2nd Edition)
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12 pages, 470 KiB  
Article
Early Effect of Supplementation with Essential Amino Acids on Cardiac Performance in Elderly Patients with Heart Failure and Sarcopenia
by Giuseppe Armentaro, Velia Cassano, Pasquale Loiacono, Carlo Fuoco, Giandomenico Severini, Carlo Alberto Pastura, Alberto Panza, Marilisa Panza, Elisa Mazza, Sofia Miceli, Arturo Pujia, Tiziana Montalcini and Angela Sciacqua
Int. J. Mol. Sci. 2025, 26(15), 7533; https://doi.org/10.3390/ijms26157533 (registering DOI) - 4 Aug 2025
Abstract
The aim of the present observational study was to evaluate the early effect of free-form essential amino acid (EAA) supplementation on cardiac and muscular performance in elderly patients with chronic heart failure (HF) with reduced ejection fraction (HFrEF) and sarcopenia, as add-on to [...] Read more.
The aim of the present observational study was to evaluate the early effect of free-form essential amino acid (EAA) supplementation on cardiac and muscular performance in elderly patients with chronic heart failure (HF) with reduced ejection fraction (HFrEF) and sarcopenia, as add-on to the optimized medical therapy (OMT) for HF. The present study included 60 elderly Caucasian patients suffering from HFrEF and sarcopenia. At the baseline and at follow-up, all patients underwent complete physical examination with the determination of the main anthropometric and hemodynamic parameters. After 6 months of supplementation with EAAs, we observed significant improvements in the parameters of sarcopenia. In addition, there was a significant improvement in glycol-metabolic parameters, and in inflammatory index as high sensitivity C-reactive protein (hs-CRP). In accordance with these results, significant decreases were observed in circulating levels of oxidative stress biomarkers Nox-2 (p < 0.001) and 8-Isoprostane (p < 0.001), and platelet aggregation biomarkers such as sP-Selectin (p < 0.001) and Gp-VI (p < 0.001). Of particular interest, after 6 months’ follow-up, there was a significant improvement in LVEF and global longitudinal strain (GLS). In conclusion, this study demonstrates that targeted nutritional intervention with EEAAs represents a viable therapeutic strategy for addressing the complex interplay between cardiac dysfunction and skeletal muscle wasting in elderly HF patients. Full article
(This article belongs to the Special Issue Molecular Pathology and Treatment of Heart Failure)
9 pages, 753 KiB  
Article
Combined Genetic and Transcriptional Study Unveils the Role of DGAT1 Gene Mutations in Congenital Diarrhea
by Jingqing Zeng, Jing Ma, Lan Wang, Zhaohui Deng and Ruen Yao
Biomedicines 2025, 13(8), 1897; https://doi.org/10.3390/biomedicines13081897 - 4 Aug 2025
Abstract
Background: Congenital diarrhea is persistent diarrhea that manifests during the neonatal period. Mutations in DGAT1, which is crucial for triglyceride synthesis and lipid absorption in the small intestine, are causal factors for congenital diarrhea. In this study, we aimed to determine [...] Read more.
Background: Congenital diarrhea is persistent diarrhea that manifests during the neonatal period. Mutations in DGAT1, which is crucial for triglyceride synthesis and lipid absorption in the small intestine, are causal factors for congenital diarrhea. In this study, we aimed to determine the value of tissue RNA sequencing (RNA-seq) for assisting with the clinical diagnosis of some genetic variants of uncertain significance. Methods: We clinically evaluated a patient with watery diarrhea, vomiting, severe malnutrition, and total parenteral nutrition dependence. Possible pathogenic variants were detected using whole-exome sequencing (WES). RNA-seq was utilized to explore the transcriptional alterations in DGAT1 variants identified by WES with unknown clinical significance, according to the American College of Medical Genetics guidelines. Systemic examinations, including endoscopic and histopathological examinations of the intestinal mucosa, were conducted to rule out other potential diagnoses. Results: We successfully diagnosed a patient with congenital diarrhea and protein-losing enteropathy caused by a DGAT1 mutation and reviewed the literature of 19 cases of children with DGAT defects. The missense mutation c.620A>G, p.Lys207Arg located in exon 15, and the intronic mutation c.1249-6T>G in DGAT1 were identified by WES. RNA-seq revealed two aberrant splicing events in the DGAT1 gene of the patient’s small intestinal tissue. Both variants lead to loss-of-function consequences and are classified as pathogenic variants of congenital diarrhea. Conclusions: Rare DGAT1 variants were identified as pathogenic evidence of congenital diarrhea, and the detection of tissue-specific mRNA splicing and transcriptional effects can provide auxiliary evidence. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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19 pages, 11665 KiB  
Article
Upregulating ANKHD1 in PS19 Mice Reduces Tau Phosphorylation and Mitigates Tau Toxicity-Induced Cognitive Deficits
by Xiaolin Tian, Nathan Le, Yuhai Zhao, Dina Alawamleh, Andrew Schwartz, Lauren Meyer, Elizabeth Helm and Chunlai Wu
Int. J. Mol. Sci. 2025, 26(15), 7524; https://doi.org/10.3390/ijms26157524 (registering DOI) - 4 Aug 2025
Abstract
Using the fly eye as a model system, we previously demonstrated that upregulation of the fly gene mask protects against FUS- and Tau-induced photoreceptor degeneration. Building upon this finding, we investigated whether the protective role of mask is conserved in mammals. To this [...] Read more.
Using the fly eye as a model system, we previously demonstrated that upregulation of the fly gene mask protects against FUS- and Tau-induced photoreceptor degeneration. Building upon this finding, we investigated whether the protective role of mask is conserved in mammals. To this end, we generated a transgenic mouse line carrying Cre-inducible ANKHD1, the human homolog of mask. Utilizing the TauP301S-PS19 mouse model for Tau-related dementia, we found that expressing ANKHD1 driven by CamK2a-Cre reduced hyperphosphorylated human Tau in 6-month-old mice. Additionally, ANKHD1 expression was associated with a trend toward reduced gliosis and preservation of the presynaptic marker Synaptophysin, suggesting a protective role of ANKHD1 against TauP301S-linked neuropathology. At 9 months of age, novel object recognition (NOR) testing revealed cognitive impairment in female, but not male, PS19 mice. Notably, co-expression of ANKHD1 restored cognitive performance in the affected female mice. Together, this study highlights the novel effect of ANKHD1 in counteracting the adverse effects induced by the mutant human Tau protein. This finding underscores ANKHD1’s potential as a unique therapeutic target for tauopathies. Full article
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13 pages, 6042 KiB  
Article
Whey Protein–Quercetin–Gellan Gum Complexes Prepared Using pH-Shift Treatment: Structural and Functional Properties
by Na Guo, Xin Zhou, Ganghua Zhou, Yimeng Zhang, Guoqing Yu, Yangliu Liu, Beibei Li, Fangyan Zhang and Guilan Zhu
Foods 2025, 14(15), 2720; https://doi.org/10.3390/foods14152720 - 3 Aug 2025
Viewed by 58
Abstract
The objectives of this study were to prepare whey protein–quercetin–gellan gum conjugates using the pH-shift method and to evaluate the impacts of varying pH values and quercetin concentrations on the interaction mechanisms and functional characteristics of the complexes. Spectroscopic analyses (fluorescence, UV-vis, and [...] Read more.
The objectives of this study were to prepare whey protein–quercetin–gellan gum conjugates using the pH-shift method and to evaluate the impacts of varying pH values and quercetin concentrations on the interaction mechanisms and functional characteristics of the complexes. Spectroscopic analyses (fluorescence, UV-vis, and FT-IR) revealed that new complexes formed under alkaline conditions. Notably, an increasing quercetin concentration led to a reduction in complex particle size and an increase in the zeta potential value, with these effects being more pronounced under alkaline conditions. The particle size was 425.7 nm, and the zeta potential value was −30.00 mV at a quercetin addition concentration of 15 umol/g protein. Additionally, the complexes formed under alkaline conditions exhibited superior foaming capacity, emulsification properties, and significantly enhanced free radical scavenging activity. The complex’s DPPH and ABTS radical scavenging rates rose by 41.57% and 57.69%, respectively. This study provides theoretical foundations and practical insights for developing protein—polyphenol systems, offering significant implications for the application of quercetin functional foods and supplements in the food science and pharmaceutical industries. Full article
(This article belongs to the Special Issue Oil and Protein Engineering and Its Applications in Food Industry)
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16 pages, 1961 KiB  
Article
A Novel Glycosylated Ferulic Acid Conjugate: Synthesis, Antioxidative Neuroprotection Activities In Vitro, and Alleviation of Cerebral Ischemia–Reperfusion Injury (CIRI) In Vivo
by Jian Chen, Yongjun Yuan, Litao Tong, Manyou Yu, Yongqing Zhu, Qingqing Liu, Junling Deng, Fengzhang Wang, Zhuoya Xiang and Chen Xia
Antioxidants 2025, 14(8), 953; https://doi.org/10.3390/antiox14080953 (registering DOI) - 3 Aug 2025
Viewed by 72
Abstract
Antioxidative neuroprotection is effective at preventing ischemic stroke (IS). Ferulic acid (FA) offers benefits in the treatment of many diseases, mostly due to its antioxidant activities. In this study, a glycosylated ferulic acid conjugate (FA-Glu), with 1,2,3-triazole as a linker and bioisostere between [...] Read more.
Antioxidative neuroprotection is effective at preventing ischemic stroke (IS). Ferulic acid (FA) offers benefits in the treatment of many diseases, mostly due to its antioxidant activities. In this study, a glycosylated ferulic acid conjugate (FA-Glu), with 1,2,3-triazole as a linker and bioisostere between glucose at the C6 position and FA at the C4 position, was designed and synthesized. The hydrophilicity and chemical stability of FA-Glu were tested. FA-Glu’s protection against DNA oxidative cleavage was tested using pBR322 plasmid DNA under the Fenton reaction. The cytotoxicity of FA-Glu was examined via the PC12 cell and bEnd.3 cell tests. Antioxidative neuroprotection was evaluated, in vitro, via a H2O2-induced PC12 cell test, measuring cell viability and ROS levels. Antioxidative alleviation of cerebral ischemia–reperfusion injury (CIRI), in vivo, was evaluated using a rat middle cerebral artery occlusion (MCAO) model. The results indicated that FA-Glu was water-soluble (LogP −1.16 ± 0.01) and chemically stable. FA-Glu prevented pBR322 plasmid DNA cleavage induced via •OH radicals (SC% 88.00%). It was a non-toxic agent based on PC12 cell and bEnd.3 cell tests results. FA-Glu significantly protected against H2O2-induced oxidative damage in the PC12 cell (cell viability 88.12%, 100 μM) and inhibited excessive cell ROS generation (45.67% at 100 μM). FA-Glu significantly reduced the infarcted brain areas measured using TTC stain observation, quantification (FA-Glu 21.79%, FA 28.49%, I/R model 43.42%), and H&E stain histological observation. It sharply reduced the MDA level (3.26 nmol/mg protein) and significantly increased the GSH level (139.6 nmol/mg protein) and SOD level (265.19 U/mg protein). With superior performance to FA, FA-Glu is a safe agent with effective antioxidative DNA and neuronal protective actions and an ability to alleviate CIRI, which should help in the prevention of IS. Full article
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18 pages, 6860 KiB  
Article
Molecular Characterization and Antiviral Function Against GCRV of Complement Factor D in Barbel Chub (Squaliobarbus curriculus)
by Yu Xiao, Zhao Lv, Yuling Wei, Mengyuan Zhang, Hong Yang, Chao Huang, Tiaoyi Xiao and Yilin Li
Fishes 2025, 10(8), 370; https://doi.org/10.3390/fishes10080370 - 2 Aug 2025
Viewed by 143
Abstract
The barbel chub (Squaliobarbus curriculus) exhibits remarkable resistance to grass carp reovirus (GCRV), a devastating pathogen in aquaculture. To reveal the molecular basis of this resistance, we investigated complement factor D (DF)—a rate-limiting serine protease governing alternative complement pathway activation. Molecular [...] Read more.
The barbel chub (Squaliobarbus curriculus) exhibits remarkable resistance to grass carp reovirus (GCRV), a devastating pathogen in aquaculture. To reveal the molecular basis of this resistance, we investigated complement factor D (DF)—a rate-limiting serine protease governing alternative complement pathway activation. Molecular cloning revealed that the barbel chub DF (ScDF) gene encodes a 1251-bp cDNA sequence translating into a 250-amino acid protein. Crucially, bioinformatic characterization identified a unique N-glycosylation site at Asn139 in ScDF, representing a structural divergence absent in grass carp (Ctenopharyngodon idella) DF (CiDF). While retaining a conserved Tryp_SPc domain harboring the catalytic triad (His61, Asp109, and Ser204) and substrate-binding residues (Asp198, Ser219, and Gly221), sequence and phylogenetic analyses confirmed ScDF’s evolutionary conservation, displaying 94.4% amino acid identity with CiDF and clustering within the Cyprinidae. Expression profiling revealed constitutive ScDF dominance in the liver, and secondary prominence was observed in the heart. Upon GCRV challenge in S. curriculus kidney (SCK) cells, ScDF transcription surged to a 438-fold increase versus uninfected controls at 6 h post-infection (hpi; p < 0.001)—significantly preceding the 168-hpi response peak documented for CiDF in grass carp. Functional validation showed that ScDF overexpression suppressed key viral capsid genes (VP2, VP5, and VP7) and upregulated the interferon regulator IRF9. Moreover, recombinant ScDF protein incubation induced interferon pathway genes and complement C3 expression. Collectively, ScDF’s rapid early induction (peaking at 6 hpi) and multi-pathway coordination may contribute to barbel chub’s GCRV resistance. These findings may provide molecular insights into the barbel chub’s high GCRV resistance compared to grass carp and novel perspectives for anti-GCRV breeding strategies in fish. Full article
(This article belongs to the Special Issue Molecular Design Breeding in Aquaculture)
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22 pages, 5123 KiB  
Article
Tailored Effects of Plasma-Activated Water on Hair Structure Through Comparative Analysis of Nitrate-Rich and Peroxide-Rich Formulations Across Different Hair Types
by Antonia de Souza Leal, Michaela Shiotani Marcondes, Ariane Leite, Douglas Leite, Clodomiro Alves Junior, Laurita dos Santos and Rodrigo Pessoa
Appl. Sci. 2025, 15(15), 8573; https://doi.org/10.3390/app15158573 (registering DOI) - 1 Aug 2025
Viewed by 181
Abstract
Plasma-activated water (PAW), enriched with reactive oxygen and nitrogen species (RONS), presents oxidative and antimicrobial characteristics with potential in cosmetic applications. This study examined the effects of two PAW formulations—nitrate-rich (PAW-N) and peroxide-rich (PAW-P)—on human hair types classified as straight (Type 1), wavy [...] Read more.
Plasma-activated water (PAW), enriched with reactive oxygen and nitrogen species (RONS), presents oxidative and antimicrobial characteristics with potential in cosmetic applications. This study examined the effects of two PAW formulations—nitrate-rich (PAW-N) and peroxide-rich (PAW-P)—on human hair types classified as straight (Type 1), wavy (Type 2), and coily/kinky (Type 4). The impact of PAW on hair structure and chemistry was evaluated using Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), UV–Vis spectrophotometry, and physicochemical analyses of the liquids (pH, ORP, conductivity, and TDS). PAW-N, with high nitrate content (~500 mg/L), low pH (2.15), and elevated conductivity (6244 µS/cm), induced significant damage to porous hair types, including disulfide bond cleavage, protein oxidation, and lipid degradation, as indicated by FTIR and EDS data. SEM confirmed severe cuticle disruption. In contrast, PAW-P, containing >25 mg/L of hydrogen peroxide and exhibiting milder acidity and lower ionic strength, caused more localized and controlled oxidation with minimal morphological damage. Straight hair showed greater resistance to both treatments, while coily and wavy hair were more susceptible, particularly to PAW-N. These findings suggest that the formulation and ionic profile of PAW should be matched to hair porosity for safe oxidative treatments, supporting the use of PAW-P as a gentler alternative in hair care technologies. Full article
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24 pages, 3888 KiB  
Article
Agronomic Biofortification: Enhancing the Grain Nutritional Composition and Mineral Content of Winter Barley (Hordeum vulgare L.) Through Foliar Nutrient Application Under Different Soil Tillage Methods
by Amare Assefa Bogale, Zoltan Kende, István Balla, Péter Mikó, Boglárka Bozóki and Attila Percze
Agriculture 2025, 15(15), 1668; https://doi.org/10.3390/agriculture15151668 - 1 Aug 2025
Viewed by 195
Abstract
Enhancing the nutritional content of crops is crucial for safeguarding human health and mitigating global hunger. A viable method for attaining this goal is the planned implementation of various agronomic practices, including tillage and nutrient provision. A field experiment was executed at the [...] Read more.
Enhancing the nutritional content of crops is crucial for safeguarding human health and mitigating global hunger. A viable method for attaining this goal is the planned implementation of various agronomic practices, including tillage and nutrient provision. A field experiment was executed at the Hungarian University of Agriculture and Life Sciences in Gödöllő in the 2023 and 2024 growing seasons. The study aimed to assess the effects of foliar nutrient supply and soil tillage methods on the grain nutritional composition and mineral content of winter barley. Employing a split-plot design with three replications, the experiment included four nutrient treatments (control, bio-cereal, bio-algae, and MgSMnZn blend) and two soil tillage types (i.e., plowing and cultivator). The results indicated that while protein content was not influenced by the main effects of nutrients and tillage, the levels of β-glucan, starch, crude ash, and moisture content were significantly (p < 0.05) affected by the nutrient treatments and by growing year, treated as a random factor. Notably, bio-algae and bio-cereal nutrients, combined with cultivator tillage, enhanced β-glucan content. All applied nutrient treatments increased the level of starch compared to the control. With regard to grain mineral content, the iron and zinc content responded to the nutrient supply, tillage, and growing year. However, applying a multiple-nutrient composition-based treatment did not increase iron and zinc levels, suggesting that individual applications may be more effective for increasing the content of these minerals in grains. Cultivator tillage improved iron and zinc levels. Moreover, manganese (Mn) and copper (Cu) were predominantly affected by nutrient availability and by growing seasons as a random factor. Therefore, to improve grain quality, this study emphasizes the significance of proper nutrient and tillage methods by focusing on the intricate relationships between agronomic techniques and environmental factors that shape barley’s nutritional profile. Full article
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14 pages, 1399 KiB  
Article
GSTM5 as a Potential Biomarker for Treatment Resistance in Prostate Cancer
by Patricia Porras-Quesada, Lucía Chica-Redecillas, Beatriz Álvarez-González, Francisco Gutiérrez-Tejero, Miguel Arrabal-Martín, Rosa Rios-Pelegrina, Luis Javier Martínez-González, María Jesús Álvarez-Cubero and Fernando Vázquez-Alonso
Biomedicines 2025, 13(8), 1872; https://doi.org/10.3390/biomedicines13081872 - 1 Aug 2025
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Abstract
Background/Objectives: Androgen deprivation therapy (ADT) is widely used to manage prostate cancer (PC), but the emergence of treatment resistance remains a major clinical challenge. Although the GST family has been implicated in drug resistance, the specific role of GSTM5 remains poorly understood. [...] Read more.
Background/Objectives: Androgen deprivation therapy (ADT) is widely used to manage prostate cancer (PC), but the emergence of treatment resistance remains a major clinical challenge. Although the GST family has been implicated in drug resistance, the specific role of GSTM5 remains poorly understood. This study investigates whether GSTM5, alone or in combination with clinical variables, can improve patient stratification based on the risk of early treatment resistance. Methods: In silico analyses were performed to examine GSTM5’s role in protein interactions, molecular pathways, and gene expression. The rs3768490 polymorphism was genotyped in 354 patients with PC, classified by ADT response. Descriptive analysis and logistic regression models were applied to evaluate associations between genotype, clinical variables, and ADT response. GSTM5 expression related to the rs3768490 genotype and ADT response was also analyzed in 129 prostate tissue samples. Results: The T/T genotype of rs3768490 was significantly associated with a lower likelihood of early ADT resistance in both individual (p = 0.0359, Odd Ratios (OR) = 0.18) and recessive models (p = 0.0491, OR = 0.21). High-risk classification according to D’Amico was strongly associated with early progression (p < 0.0004; OR > 5.4). Combining genotype and clinical risk improved predictive performance, highlighting their complementary value in stratifying patients by treatment response. Additionally, GSTM5 expression was slightly higher in T/T carriers, suggesting a potential protective role against ADT resistance. Conclusions: The T/T genotype of rs3768490 may protect against ADT resistance by modulating GSTM5 expression in PC. These preliminary findings highlight the potential of integrating genetic biomarkers into clinical models for personalized treatment strategies, although further studies are needed to validate these observations. Full article
(This article belongs to the Special Issue Molecular Biomarkers of Tumors: Advancing Genetic Studies)
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21 pages, 3146 KiB  
Article
TnP as a Multifaceted Therapeutic Peptide with System-Wide Regulatory Capacity
by Geonildo Rodrigo Disner, Emma Wincent, Carla Lima and Monica Lopes-Ferreira
Pharmaceuticals 2025, 18(8), 1146; https://doi.org/10.3390/ph18081146 - 1 Aug 2025
Viewed by 131
Abstract
Background: The candidate therapeutic peptide TnP demonstrates broad, system-level regulatory capacity, revealed through integrated network analysis from transcriptomic data in zebrafish. Our study primarily identifies TnP as a multifaceted modulator of drug metabolism, wound healing, proteolytic activity, and pigmentation pathways. Results: Transcriptomic profiling [...] Read more.
Background: The candidate therapeutic peptide TnP demonstrates broad, system-level regulatory capacity, revealed through integrated network analysis from transcriptomic data in zebrafish. Our study primarily identifies TnP as a multifaceted modulator of drug metabolism, wound healing, proteolytic activity, and pigmentation pathways. Results: Transcriptomic profiling of TnP-treated larvae following tail fin amputation revealed 558 differentially expressed genes (DEGs), categorized into four functional networks: (1) drug-metabolizing enzymes (cyp3a65, cyp1a) and transporters (SLC/ABC families), where TnP alters xenobiotic processing through Phase I/II modulation; (2) cellular trafficking and immune regulation, with upregulated myosin genes (myhb/mylz3) enhancing wound repair and tlr5-cdc42 signaling fine-tuning inflammation; (3) proteolytic cascades (c6ast4, prss1) coupled to autophagy (ulk1a, atg2a) and metabolic rewiring (g6pca.1-tg axis); and (4) melanogenesis-circadian networks (pmela/dct-fbxl3l) linked to ubiquitin-mediated protein turnover. Key findings highlight TnP’s unique coordination of rapid (protease activation) and sustained (metabolic adaptation) responses, enabled by short network path lengths (1.6–2.1 edges). Hub genes, such as nr1i2 (pxr), ppara, and bcl6aa/b, mediate crosstalk between these systems, while potential risks—including muscle hypercontractility (myhb overexpression) or cardiovascular effects (ace2-ppp3ccb)—underscore the need for targeted delivery. The zebrafish model validated TnP-conserved mechanisms with human relevance, particularly in drug metabolism and tissue repair. TnP’s ability to synchronize extracellular matrix remodeling, immune resolution, and metabolic homeostasis supports its development for the treatment of fibrosis, metabolic disorders, and inflammatory conditions. Conclusions: Future work should focus on optimizing tissue-specific delivery and assessing genetic variability to advance clinical translation. This system-level analysis positions TnP as a model example for next-generation multi-pathway therapeutics. Full article
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