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Search Results (1,928)

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23 pages, 11168 KiB  
Article
Persistent Inflammation, Maladaptive Remodeling, and Fibrosis in the Kidney Following Long COVID-like MHV-1 Mouse Model
by Rajalakshmi Ramamoorthy, Anna Rosa Speciale, Emily M. West, Hussain Hussain, Nila Elumalai, Klaus Erich Schmitz Abe, Madesh Chinnathevar Ramesh, Pankaj B. Agrawal, Arumugam R. Jayakumar and Michael J. Paidas
Diseases 2025, 13(8), 246; https://doi.org/10.3390/diseases13080246 (registering DOI) - 5 Aug 2025
Abstract
Background: Accumulating evidence indicates that SARS-CoV-2 infection results in long-term multiorgan complications, with the kidney being a primary target. This study aimed to characterize the long-term transcriptomic changes in the kidney following coronavirus infection using a murine model of MHV-1-induced SARS-like illness and [...] Read more.
Background: Accumulating evidence indicates that SARS-CoV-2 infection results in long-term multiorgan complications, with the kidney being a primary target. This study aimed to characterize the long-term transcriptomic changes in the kidney following coronavirus infection using a murine model of MHV-1-induced SARS-like illness and to evaluate the therapeutic efficacy of SPIKENET (SPK). Methods: A/J mice were infected with MHV-1. Renal tissues were collected and subjected to immunofluorescence analysis and Next Generation RNA Sequencing to identify differentially expressed genes associated with acute and chronic infection. Bioinformatic analyses, including PCA, volcano plots, and GO/KEGG pathway enrichment, were performed. A separate cohort received SPK treatment, and comparative transcriptomic profiling was conducted. Gene expression profile was further confirmed using real-time PCR. Results: Acute infection showed the upregulation of genes involved in inflammation and fibrosis. Long-term MHV-1 infection led to the sustained upregulation of genes involved in muscle regeneration, cytoskeletal remodeling, and fibrotic responses. Notably, both expression and variability of SLC22 and SLC22A8, key proximal tubule transporters, were reduced, suggesting a loss of segment-specific identity. Further, SLC12A1, a critical regulator of sodium reabsorption and blood pressure, was downregulated and is associated with the onset of polyuria and hydronephrosis. SLC transporters exhibited expression patterns consistent with tubular dysfunction and inflammation. These findings suggest aberrant activation of myogenic pathways and structural proteins in renal tissues, consistent with a pro-fibrotic phenotype. In contrast, SPK treatment reversed the expression of most genes, thereby restoring the gene profiles to those observed in control mice. Conclusions: MHV-1-induced long COVID is associated with persistent transcriptional reprogramming in the kidney, indicative of chronic inflammation, cytoskeletal dysregulation, and fibrogenesis. SPK demonstrates robust therapeutic potential by normalizing these molecular signatures and preventing long-term renal damage. These findings underscore the relevance of the MHV-1 model and support further investigation of SPK as a candidate therapy for COVID-19-associated renal sequelae. Full article
(This article belongs to the Special Issue COVID-19 and Global Chronic Disease 2025: New Challenges)
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29 pages, 21916 KiB  
Article
Pentoxifylline and Norcantharidin Synergistically Suppress Melanoma Growth in Mice: A Multi-Modal In Vivo and In Silico Study
by Israel Lara-Vega, Minerva Nájera-Martínez and Armando Vega-López
Int. J. Mol. Sci. 2025, 26(15), 7522; https://doi.org/10.3390/ijms26157522 (registering DOI) - 4 Aug 2025
Abstract
Melanoma is a highly aggressive skin cancer with limited therapeutic response. Targeting intracellular signaling pathways and promoting tumor cell differentiation are promising therapeutic strategies. Pentoxifylline (PTX) and norcantharidin (NCTD) have demonstrated antitumor properties, but their combined mechanisms of action in melanoma remain poorly [...] Read more.
Melanoma is a highly aggressive skin cancer with limited therapeutic response. Targeting intracellular signaling pathways and promoting tumor cell differentiation are promising therapeutic strategies. Pentoxifylline (PTX) and norcantharidin (NCTD) have demonstrated antitumor properties, but their combined mechanisms of action in melanoma remain poorly understood. The effects of PTX (30 and 60 mg/kg) and NCTD (0.75 and 3 mg/kg), administered alone or in combination, in a DBA/2J murine B16-F1 melanoma model via intraperitoneal and intratumoral (IT) routes were evaluated. Tumor growth was monitored, and molecular analyses included RNA sequencing and immunofluorescence quantification of PI3K, AKT1, mTOR, ERBB2, BRAF, and MITF protein levels, and molecular docking simulations were performed. In the final stage of the experiment, combination therapy significantly reduced tumor volume compared to monotherapies, with the relative tumor volume decreasing from 18.1 ± 1.2 (SD) in the IT Control group to 0.6 ± 0.1 (SD) in the IT combination-treated group (n = 6 per group; p < 0.001). RNA-seq revealed over 3000 differentially expressed genes in intratumoral treatments, with enrichment in pathways related to oxidative stress, immune response, and translation regulation (KEGG and Reactome analyses). Minimal transcript-level changes were observed for BRAF and PI3K/AKT/mTOR genes; however, immunofluorescence showed reduced total and phosphorylated levels of PI3K, AKT1, mTOR, BRAF, and ERBB2. MITF protein levels and pigmentation increased, especially in PTX-treated groups, indicating enhanced melanocytic differentiation. Docking analyses predicted direct binding of both drugs to PI3K, AKT1, mTOR, and BRAF, with affinities ranging from −5.7 to −7.4 kcal/mol. The combination of PTX and NCTD suppresses melanoma progression through dual mechanisms: inhibition of PI3K/AKT/mTOR signaling and promotion of tumor cell differentiation. Full article
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15 pages, 611 KiB  
Review
Role of Dyadic Proteins in Proper Heart Function and Disease
by Carter Liou and Michael T. Chin
Int. J. Mol. Sci. 2025, 26(15), 7478; https://doi.org/10.3390/ijms26157478 (registering DOI) - 2 Aug 2025
Viewed by 162
Abstract
Cardiovascular disease encompasses a wide group of conditions that affect the heart and blood vessels. Of these diseases, cardiomyopathies and arrhythmias specifically have been well-studied in their relationship to cardiac dyads, nanoscopic structures that connect electrical signals to muscle contraction. The proper development [...] Read more.
Cardiovascular disease encompasses a wide group of conditions that affect the heart and blood vessels. Of these diseases, cardiomyopathies and arrhythmias specifically have been well-studied in their relationship to cardiac dyads, nanoscopic structures that connect electrical signals to muscle contraction. The proper development and positioning of dyads is essential in excitation–contraction (EC) coupling and, thus, beating of the heart. Three proteins, namely CMYA5, JPH2, and BIN1, are responsible for maintaining the dyadic cleft between the T-tubule and junctional sarcoplasmic reticulum (jSR). Various other dyadic proteins play integral roles in the primary function of the dyad—translating a propagating action potential (AP) into a myocardial contraction. Ca2+, a secondary messenger in this process, acts as an allosteric activator of the sarcomere, and its cytoplasmic concentration is regulated by the dyad. Loss-of-function mutations have been shown to result in cardiomyopathies and arrhythmias. Adeno-associated virus (AAV) gene therapy with dyad components can rescue dyadic dysfunction, which results in cardiomyopathies and arrhythmias. Overall, the dyad and its components serve as essential mediators of calcium homeostasis and excitation–contraction coupling in the mammalian heart and, when dysfunctional, result in significant cardiac dysfunction, arrhythmias, morbidity, and mortality. Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Histopathological and Molecular Diagnostics)
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12 pages, 1252 KiB  
Article
Low Dietary Folate Increases Developmental Delays in the Litters of Mthfr677TT Mice
by Karen E. Christensen, Marie-Lou Faquette, Vafa Keser, Alaina M. Reagan, Aaron T. Gebert, Teodoro Bottiglieri, Gareth R. Howell and Rima Rozen
Nutrients 2025, 17(15), 2536; https://doi.org/10.3390/nu17152536 - 1 Aug 2025
Viewed by 194
Abstract
Background/Objectives: Low folate intake before and during pregnancy increases the risk of neural tube defects and other adverse outcomes. Gene variants such as MTHFR 677C>T (rs1801133) may increase risks associated with suboptimal folate intake. Our objective was to use BALB/cJ Mthfr677C>T [...] Read more.
Background/Objectives: Low folate intake before and during pregnancy increases the risk of neural tube defects and other adverse outcomes. Gene variants such as MTHFR 677C>T (rs1801133) may increase risks associated with suboptimal folate intake. Our objective was to use BALB/cJ Mthfr677C>T mice to evaluate the effects of the TT genotype and low folate diets on embryonic development and MTHFR protein expression in pregnant mice. Methods: Female 677CC (mCC) and 677TT (mTT) mice were fed control (2 mg folic acid/kg (2D)), 1 mg folic acid/kg (1D) and 0.3 mg folic acid/kg (0.3D) diets before and during pregnancy. Embryos and maternal tissues were collected at embryonic day 10.5. Embryos were examined for developmental delays and defects. Methyltetrahydrofolate (methylTHF) and total homocysteine (tHcy) were measured in maternal plasma, and MTHFR protein expression was evaluated in maternal liver. Results: MethylTHF decreased due to the experimental diets and mTT genotype. tHcy increased due to 0.3D and mTT genotype; mTT 0.3D mice had significantly higher tHcy than the other groups. MTHFR expression was lower in mTT liver than mCC. MTHFR protein expression increased due to low folate diets in mCC mice, whereas in mTT mice, MTHFR expression increased only due to 1D. Developmental delays were increased in the litters of mTT mice fed 1D and 0.3D. Conclusions: The Mthfr677C>T mouse models the effects of the MTHFR 677TT genotype in humans and provides a folate-responsive model for examination of the effects of folate intake and the MTHFR 677C>T variant during gestation. Full article
(This article belongs to the Section Micronutrients and Human Health)
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24 pages, 958 KiB  
Article
Optimizing Aspergillus oryzae Inoculation Dosage and Fermentation Duration for Enhanced Protein Content in Soybean Meal and Its Influence on Dog Food Extrusion
by Youhan Chen, Thomas Weiss, Donghai Wang, Sajid Alavi and Charles Gregory Aldrich
Processes 2025, 13(8), 2441; https://doi.org/10.3390/pr13082441 - 1 Aug 2025
Viewed by 281
Abstract
This study aimed to optimize the inoculation dosage and fermentation duration to enhance the protein content and reduce soluble oligosaccharides in soybean meal using Aspergillus oryzae and assessed its performance in dog food extrusion. A 3 × 5 factorial design was used to [...] Read more.
This study aimed to optimize the inoculation dosage and fermentation duration to enhance the protein content and reduce soluble oligosaccharides in soybean meal using Aspergillus oryzae and assessed its performance in dog food extrusion. A 3 × 5 factorial design was used to determine the optimal fermentation conditions. These conditions were applied to ferment soybean meal in bulk for nutritional analysis. Finally, the impact of fermentation on extrusion processing was assessed by formulating and extruding four diets: SBM (30% soybean meal), AMF (30% soybean meal with 1% Amaferm®A. oryzae biomass), FSBM (30% fermented soybean meal), and SPI (18% soy protein isolate). Diets were extruded with a single-screw extruder, and physical characteristics of kibbles, particle size distribution, and viscosity of raw mixes were analyzed. The optimal fermentation conditions were 1 × 104 spore/g substrate for 36 h, which increased the crude protein content by 4.63% DM, methionine and cysteine total content by 0.15% DM, and eliminated sucrose, while significantly reducing stachyose, raffinose, and verbascose (95.22, 87.37, and 41.82%, respectively). The extrusion results showed that FSBM had intermediate specific mechanical energy (SME), in-barrel moisture requirements, and sectional expansion index (198.7 kJ/kg, 28.2%, and 1.80, respectively) compared with SBM (83.7 kJ/kg, 34.5%, and 1.30, respectively) and SPI (305.3 kJ/kg, 33.5%, and 2.55, respectively). The FSBM also exhibited intermediate particle size distribution and the least raw mix viscosity. These findings demonstrate that A. oryzae fermentation enhances the nutrient profile of soybean meal while improving extrusion efficiency and kibble quality, supporting its potential use as a sustainable pet food ingredient. Full article
(This article belongs to the Special Issue Feature Papers in the "Food Process Engineering" Section)
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17 pages, 2582 KiB  
Article
Transcriptional Regulatory Mechanisms of Blueberry Endophytes in Enhancing Aluminum (Al) Tolerance in Pumpkins
by Qiang Chen, Xinqi Guo, Hongbo Pang, Ying Zhang, Haiyan Lv and Chong Zhang
Horticulturae 2025, 11(8), 887; https://doi.org/10.3390/horticulturae11080887 (registering DOI) - 1 Aug 2025
Viewed by 184
Abstract
Aluminum (Al) stress is an important factor that inhibits crop growth in acidic soils and poses a threat to pumpkin (Cucurbita moschata) production. In this study, we investigated the effect of endophyte (endophyte) strain J01 of blueberry (Vaccinium uliginosum) [...] Read more.
Aluminum (Al) stress is an important factor that inhibits crop growth in acidic soils and poses a threat to pumpkin (Cucurbita moschata) production. In this study, we investigated the effect of endophyte (endophyte) strain J01 of blueberry (Vaccinium uliginosum) on the growth, development, and transcriptional regulatory mechanisms of pumpkin under aluminum stress. The results showed that the blueberry endophyte strain J01 significantly increased the root length of pumpkin under aluminum stress, promoted the growth of lateral roots, and increased root vigor; strain J01 reduced the content of MDA and the relative conductivity in the root system; strain J01 enhanced the activities of superoxide dismutase and catalase in the root system but inhibited ascorbate peroxidase activity. Transcriptome analysis further revealed that strain J01 significantly regulated the expression of key genes associated with aluminum tolerance, including the upregulation of transporter protein genes (aluminum-activated malate transporter and aquaporin), affecting the gene expression levels of genes encoding antioxidant enzymes (ascorbate peroxidase and glutathione S-transferase) and cell wall modification genes (xyloglucan endotransglucosylase/hydrolase and pectin methylesterase). This study provides a theoretical basis and practical guidance for using microbial resources to improve aluminum tolerance in cucurbit crops. Full article
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14 pages, 6123 KiB  
Article
Effects of Near-Infrared Diode Laser Irradiation on Pain Relief and Neuropeptide Markers During Experimental Tooth Movement in the Periodontal Ligament Tissues of Rats: A Pilot Study
by Kanako Okazaki, Ayaka Nakatani, Ryo Kunimatsu, Isamu Kado, Shuzo Sakata, Hirotaka Kiridoshi and Kotaro Tanimoto
Int. J. Mol. Sci. 2025, 26(15), 7404; https://doi.org/10.3390/ijms26157404 - 31 Jul 2025
Viewed by 145
Abstract
Pain following orthodontic treatment is the chief complaint of patients undergoing this form of treatment. Although the use of diode lasers has been suggested for pain reduction, the mechanism of laser-induced analgesic effects remains unclear. Neuropeptides, such as substance P (SP) and calcitonin [...] Read more.
Pain following orthodontic treatment is the chief complaint of patients undergoing this form of treatment. Although the use of diode lasers has been suggested for pain reduction, the mechanism of laser-induced analgesic effects remains unclear. Neuropeptides, such as substance P (SP) and calcitonin gene-related peptide (CGRP), contribute to the transmission and maintenance of inflammatory pain. Heat shock protein (HSP) 70 plays a protective role against various stresses, including orthodontic forces. This study aimed to examine the effects of diode laser irradiation on neuropeptides and HSP 70 expression in periodontal tissues induced by experimental tooth movement (ETM). For inducing ETM for 24 h, 50 g of orthodontic force was applied using a nickel–titanium closed-coil spring to the upper left first molar and the incisors of 20 male Sprague Dawley rats (7 weeks old). The right side without ETM treatment was considered the untreated control group. In 10 rats, diode laser irradiation was performed on the buccal and palatal sides of the first molar for 90 s with a total energy of 100.8 J/cm2. A near-infrared (NIR) laser with a 808 nm wavelength, 7 W peak power, 560 W average power, and 20 ms pulse width was used for the experiment. We measured the number of facial groomings and vacuous chewing movements (VCMs) in the ETM and ETM + laser groups. Immunohistochemical staining of the periodontal tissue with SP, CGRP, and HSP 70 was performed. The number of facial grooming and VCM periods significantly decreased in the ETM + laser group compared to the ETM group. Moreover, the ETM + laser group demonstrated significant suppression of SP, CGRP, and HSP 70 expression. These results suggest that the diode laser demonstrated analgesic effects on ETM-induced pain by inhibiting SP and CGRP expression, and decreased HSP 70 expression shows alleviation of cell damage. Thus, although further validation is warranted for human applications, an NIR diode laser can be used for reducing pain and neuropeptide markers during orthodontic tooth movement. Full article
(This article belongs to the Special Issue Advances in Photobiomodulation Therapy)
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16 pages, 3054 KiB  
Article
Naringenin Inhibits Enterotoxigenic Escherichia coli-Induced Ferroptosis via Targeting HSP90 in IPEC-J2 Cells
by Pengxin Jiang, Kangping Liu, Yanan Cui, Puyu Liu, Xutao Wang, Zijuan Hou, Jiamei Cui, Ning Chen, Jinghui Fan, Jianguo Li, Yuzhu Zuo and Yan Li
Antioxidants 2025, 14(8), 914; https://doi.org/10.3390/antiox14080914 - 25 Jul 2025
Viewed by 324
Abstract
Enterotoxigenic Escherichia coli (ETEC) leads to severe diarrhea in piglets. Naringenin (Nar), a natural flavonoid compound, is known for its antibacterial and anti-antioxidant properties. However, the protective effects of Nar against ETEC-induced diarrhea have not been reported yet. This study investigated the protective [...] Read more.
Enterotoxigenic Escherichia coli (ETEC) leads to severe diarrhea in piglets. Naringenin (Nar), a natural flavonoid compound, is known for its antibacterial and anti-antioxidant properties. However, the protective effects of Nar against ETEC-induced diarrhea have not been reported yet. This study investigated the protective mechanisms of Nar against ETEC infection in porcine intestinal epithelial cells (IPEC-J2). ETEC infection induced oxidative stress and ferroptosis in IPEC-J2 cells by elevating intracellular iron content and ROS accumulation, increasing MDA levels, downregulating SOD activity and GPX4 expression, and upregulating the transcription of CHAC1 and SLC7A11. In contrast, Nar suppressed ETEC-induced ferroptosis of IPEC-J2 cells by inhibiting the SLC7A11/GPX4 pathway. Specifically, Nar mitigated mitochondrial damage, reduced intracellular iron levels and ROS accumulation, and ultimately reversed the oxidative stress. Network pharmacology and molecular docking identified heat-shock protein 90 (HSP90) as a potential target of Nar. Overexpression and knockdown experiments revealed that ETEC-induced ferroptosis was mediated by upregulation of HSP90, while the protective effects of Nar against ETEC-induced ferroptosis were dependent on the downregulation of HSP90. In conclusion, Nar targets host HSP90 to protect IPEC-J2 cells from ferroptosis caused by ETEC infection. This study demonstrates that Nar is a potent antioxidant natural compound with potential for preventing ETEC-induced intestinal damage. Full article
(This article belongs to the Special Issue Oxidative Stress in Livestock and Poultry—3rd Edition)
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20 pages, 2822 KiB  
Article
Nanoparticle Formulation Generated from DDGS and Its Anthraquinone Synthesis Elicitation in Rubia tinctorum Hairy Roots
by Gonzalo Galaburri, Yazmín R. Kalapuj, María Perassolo, Julián Rodríguez Talou, Patricio G. Márquez, Romina J. Glisoni, Antonia Infantes-Molina, Enrique Rodríguez-Castellón and Juan M. Lázaro-Martínez
Polymers 2025, 17(15), 2021; https://doi.org/10.3390/polym17152021 - 24 Jul 2025
Viewed by 290
Abstract
A nanoparticle formulation was generated from distiller dried grains with solubles (DDGS), and its effect on the production of anthraquinones (AQs) was evaluated on Rubia tinctorum hairy roots. The DDGS material was washed with water and ethyl acetate to remove mainly the soluble [...] Read more.
A nanoparticle formulation was generated from distiller dried grains with solubles (DDGS), and its effect on the production of anthraquinones (AQs) was evaluated on Rubia tinctorum hairy roots. The DDGS material was washed with water and ethyl acetate to remove mainly the soluble organic/inorganic molecules and reduce the fat content, respectively, followed by an alkaline treatment to remove the polysaccharides. The resulting alkaline solutions were then lyophilized and redispersed in deionized water to generate a monodispersed nanoparticulate formulation (DDGS-NP) with a hydrodynamic diameter and zeta potential of 227 ± 42 nm and −53 ± 7 mV, respectively. The formulation demonstrated good colloidal stability over time, and sterilized DDGS-NPs maintained comparable physicochemical properties. The nanoparticles were enriched in protein fractions, unsaturated fatty acids, and orthophosphate anion components from DDGS, as determined by solid-state Nuclear Magnetic Resonance (NMR), X-ray photoelectron spectroscopy (XPS), organic elemental analysis (OEA), and inductively coupled plasma optical emission spectrometry (ICP-OES) techniques. The DDGS-NPs were tested at different concentrations on Rubia tinctorum hairy roots, in comparison to or in combination with methyl jasmonate (MeJ), for their capacity to induce the production of AQs. All DDGS-NP concentrations increased the production of specific AQs to 7.7 (100 mg L−1), 7.8 (200 mg L−1), and 9.3 µmol/gFW (500 mg L−1), with an extracellular AQ accumulation of 18 µM for the highest DDGS-NP concentration, in comparison with the control hairy roots (~2 µM AQ). The plant growth was not affected at any of the tested nanoparticle concentrations. Interestingly, the combination of DDGS-NPs and MeJ resulted in the highest extracellular AQ accumulation in R. tinctorum root cultures. Full article
(This article belongs to the Section Polymer Composites and Nanocomposites)
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18 pages, 2540 KiB  
Article
Anti-Inflammatory, Antioxidant, and Reparative Effects of Casearia sylvestris Leaf Derivatives on Periodontium In Vitro
by Angélica L. R. Pavanelli, Maria Eduarda S. Lopes, André T. Reis, Flávio A. Carvalho, Sven Zalewski, André G. dos Santos, Joni A. Cirelli, James Deschner and Andressa V. B. Nogueira
Antioxidants 2025, 14(8), 901; https://doi.org/10.3390/antiox14080901 - 23 Jul 2025
Viewed by 327
Abstract
Gingival inflammation compromises the integrity of the gingival epithelium and the underlying tissues, highlighting the need for adjuvant therapies with immunomodulatory and healing properties. Casearia sylvestris, a medicinal plant known as guaçatonga, is traditionally used to treat inflammatory lesions. This study aimed [...] Read more.
Gingival inflammation compromises the integrity of the gingival epithelium and the underlying tissues, highlighting the need for adjuvant therapies with immunomodulatory and healing properties. Casearia sylvestris, a medicinal plant known as guaçatonga, is traditionally used to treat inflammatory lesions. This study aimed to investigate the effects of C. sylvestris on the synthesis of pro- and anti-inflammatory, proteolytic, and antioxidant molecules and on wound healing in epithelial cells. A human telomerase-immortalized gingival keratinocyte cell line (TIGKs) was used, and cells were exposed to Escherichia coli lipopolysaccharide (LPS) in the presence and absence of C. sylvestris extract, its diterpene-concentrated fraction, and its clerodane diterpene casearin J for 24 h and 48 h. Gene expression and protein synthesis were analyzed by RT-qPCR and ELISA, respectively. Nitric oxide (NO) and NF-κB activation were analyzed by Griess reaction and immunofluorescence, respectively. Additionally, cell viability was evaluated by alamarBlue® assay, and an automated scratch assay was used for wound healing. LPS significantly increased the expression of cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-17), proteases (MMP-1 and MMP-13), iNOS as well as NO synthesis, and triggered NF-κB nuclear translocation. It also reduced IL-4 expression, cell viability, and cellular wound repopulation. Treatment with C. sylvestris derivatives significantly abrogated all aforementioned LPS-induced effects by 80–100%. Furthermore, even at higher concentrations, C. sylvestris did not affect cell viability, thus proving the safety of its derivatives. C. sylvestris exerts anti-inflammatory, antiproteolytic, and antioxidant effects on gingival keratinocytes, highlighting its potential as a valuable adjunct in the prevention and treatment of periodontal diseases. Full article
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25 pages, 2959 KiB  
Article
Synthesis, Characterization, HSA/DNA Binding, and Cytotoxic Activity of [RuCl26-p-cymene)(bph-κN)] Complex
by Stefan Perendija, Dušan Dimić, Thomas Eichhorn, Aleksandra Rakić, Luciano Saso, Đura Nakarada, Dragoslava Đikić, Teodora Dragojević, Jasmina Dimitrić Marković and Goran N. Kaluđerović
Molecules 2025, 30(15), 3088; https://doi.org/10.3390/molecules30153088 - 23 Jul 2025
Viewed by 229
Abstract
A novel ruthenium(II) complex, [RuCl26-p-cymene)(bph-κN)] (1), was synthesized and structurally characterized using FTIR and NMR spectroscopy. Density functional theory (DFT) calculations supported the proposed geometry and allowed for comparative analysis of experimental and [...] Read more.
A novel ruthenium(II) complex, [RuCl26-p-cymene)(bph-κN)] (1), was synthesized and structurally characterized using FTIR and NMR spectroscopy. Density functional theory (DFT) calculations supported the proposed geometry and allowed for comparative analysis of experimental and theoretical spectroscopic data. The interaction of complex 1 with human serum albumin (HSA) and calf thymus DNA was investigated through fluorescence quenching experiments, revealing spontaneous binding driven primarily by hydrophobic interactions. The thermodynamic parameters indicated mixed quenching mechanisms in both protein and DNA systems. Ethidium bromide displacement assays and molecular docking simulations confirmed DNA intercalation as the dominant binding mode, with a Gibbs free binding energy of −34.1 kJ mol−1. Antioxidant activity, assessed by EPR spectroscopy, demonstrated effective scavenging of hydroxyl and ascorbyl radicals. In vitro cytotoxicity assays against A375, MDA-MB-231, MIA PaCa-2, and SW480 cancer cell lines revealed selective activity, with pancreatic and colorectal cells showing the highest sensitivity. QTAIM analysis provided insight into metal–ligand bonding characteristics and intramolecular stabilization. These findings highlight the potential of 1 as a promising candidate for further development as an anticancer agent, particularly against multidrug-resistant tumors. Full article
(This article belongs to the Special Issue Transition Metal Complexes with Bioactive Ligands)
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24 pages, 12430 KiB  
Article
DNAJ Homolog Subfamily C Member 11 Stabilizes SARS-CoV-2 NSP3 to Promote Double-Membrane Vesicle Formation
by Shuying Chen, Shanrong Yang, Xiaoning Li, Junqi Xiang, Jiangyu Cai, Yaokai Wang, Qingqing Li, Na Zang, Jiaxu Wang, Jian Shang and Yushun Wan
Viruses 2025, 17(8), 1025; https://doi.org/10.3390/v17081025 - 22 Jul 2025
Viewed by 381
Abstract
Coronaviruses, particularly those classified as highly pathogenic species, pose a significant threat to global health. These viruses hijack host cellular membranes and proteins to facilitate their replication, primarily through the formation of replication organelles (ROs). However, the precise regulatory mechanisms underlying RO formation [...] Read more.
Coronaviruses, particularly those classified as highly pathogenic species, pose a significant threat to global health. These viruses hijack host cellular membranes and proteins to facilitate their replication, primarily through the formation of replication organelles (ROs). However, the precise regulatory mechanisms underlying RO formation remain poorly understood. To elucidate these mechanisms, we conducted mass spectrometry analyses, identifying interactions between the host protein DnaJ homolog subfamily C member 11 (DNAJC11) and the SARS-CoV-2 nonstructural protein 3 (NSP3) protein. Notably, results showed that DNAJC11 depletion reduces SARS-CoV-2 infection, indicating possible positive regulatory involvement. But the ectopic expression of DNAJC11 did not lead to marked alterations in immune or inflammatory responses. DNAJC11 enhanced NSP3 expression stability through endogenous apoptosis pathways and facilitated its interaction with NSP4, thereby promoting the formation of double-membrane vesicles (DMVs). Knockdown of DNAJC11 reduced DMV number and size, accompanied by dysregulation of the endoplasmic reticulum and mitochondria. However, supplementation with DNAJC11 restored both DMV number and size. These findings provide novel insights into the role of DNAJC11 as a host factor that modulates DMV formation and supports SARS-CoV-2 replication by targeting the NSP3 protein. This study advances our understanding of the molecular interactions between host and viral components and highlights DNAJC11 as a potential target for antiviral interventions. Full article
(This article belongs to the Section Coronaviruses)
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15 pages, 766 KiB  
Article
Photobiomodulation Therapy Reduces Oxidative Stress and Inflammation to Alleviate the Cardiotoxic Effects of Doxorubicin in Human Stem Cell-Derived Ventricular Cardiomyocytes
by Guilherme Rabelo Nasuk, Leonardo Paroche de Matos, Allan Luís Barboza Atum, Bruna Calixto de Jesus, Julio Gustavo Cardoso Batista, Gabriel Almeida da Silva, Antonio Henrique Martins, Maria Laura Alchorne Trivelin, Cinthya Cosme Gutierrez Duran, Ana Paula Ligeiro de Oliveira, Renato de Araújo Prates, Rodrigo Labat Marcos, Stella Regina Zamuner, Ovidiu Constantin Baltatu and José Antônio Silva
Biomedicines 2025, 13(7), 1781; https://doi.org/10.3390/biomedicines13071781 - 21 Jul 2025
Viewed by 435
Abstract
Background/Objectives: Doxorubicin (DOX), a widely used anthracycline chemotherapeutic agent, is recognized for its efficacy in treating various malignancies. However, its clinical application is critically limited due to dose-dependent cardiotoxicity, predominantly induced by oxidative stress and compromised antioxidant defenses. Photobiomodulation (PBM), a non-invasive intervention [...] Read more.
Background/Objectives: Doxorubicin (DOX), a widely used anthracycline chemotherapeutic agent, is recognized for its efficacy in treating various malignancies. However, its clinical application is critically limited due to dose-dependent cardiotoxicity, predominantly induced by oxidative stress and compromised antioxidant defenses. Photobiomodulation (PBM), a non-invasive intervention that utilizes low-intensity light, has emerged as a promising therapeutic modality in regenerative medicine, demonstrating benefits such as enhanced tissue repair, reduced inflammation, and protection against oxidative damage. This investigation sought to evaluate the cardioprotective effects of PBM preconditioning in human-induced pluripotent stem cell-derived ventricular cardiomyocytes (hiPSC-vCMs) subjected to DOX-induced toxicity. Methods: Human iPSC-vCMs were allocated into three experimental groups: control cells (untreated), DOX-treated cells (exposed to 2 μM DOX for 24 h), and PBM+DOX-treated cells (preconditioned with PBM, utilizing 660 nm ±10 nm LED light at an intensity of 10 mW/cm2 for 500 s, delivering an energy dose of 5 J/cm2, followed by DOX exposure). Cell viability assessments were conducted in conjunction with evaluations of oxidative stress markers, including antioxidant enzyme activities and malondialdehyde (MDA) levels. Furthermore, transcriptional profiling of 40 genes implicated in cardiac dysfunction was performed using TaqMan quantitative polymerase chain reaction (qPCR), complemented by analyses of protein expression for markers of cardiac stress, inflammation, and apoptosis. Results: Exposure to DOX markedly reduced the viability of hiPSC-vCMs. The cells exhibited significant alterations in the expression of 32 out of 40 genes (80%) after DOX exposure, reflecting the upregulation of markers associated with apoptosis, inflammation, and adverse cardiac remodeling. PBM preconditioning partially restored the cell viability, modulating the expression of 20 genes (50%), effectively counteracting a substantial proportion of the dysregulation induced by DOX. Notably, PBM enhanced the expression of genes responsible for antioxidant defense, augmented antioxidant enzyme activity, and reduced oxidative stress indicators such as MDA levels. Additional benefits included downregulating stress-related mRNA markers (HSP1A1 and TNC) and apoptotic markers (BAX and TP53). PBM also demonstrated gene reprogramming effects in ventricular cells, encompassing regulatory changes in NPPA, NPPB, and MYH6. PBM reduced the protein expression levels of IL-6, TNF, and apoptotic markers in alignment with their corresponding mRNA expression profiles. Notably, PBM preconditioning showed a diminished expression of BNP, emphasizing its positive impact on mitigating cardiac stress. Conclusions: This study demonstrates that PBM preconditioning is an effective strategy for reducing DOX-induced chemotherapy-related cardiotoxicity by enhancing cell viability and modulating signaling pathways associated with oxidative stress, as well as inflammatory and hypertrophic markers. Full article
(This article belongs to the Special Issue Pathological Biomarkers in Precision Medicine)
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27 pages, 8396 KiB  
Article
Biosynthesis of Zinc Oxide Nanostructures Using Leaf Extract of Azadirachta indica: Characterizations and In Silico and Nematicidal Potentials
by Gulrana Khuwaja, Anis Ahmad Chaudhary, Abadi M. Mashlawi, Abdullah Ali Alamri, Faris Alfifi, Kahkashan Anjum, Md Shamsher Alam, Mohammad Intakhab Alam, Syed Kashif Ali, Nadeem Raza, Mohamed A. M. Ali and Mohd Imran
Catalysts 2025, 15(7), 693; https://doi.org/10.3390/catal15070693 - 21 Jul 2025
Viewed by 465
Abstract
Biosynthesized ZnO nanostructures were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), ultraviolet–visible (UV-vis) spectroscopy, and Fourier transform–infrared (FT-IR) spectroscopy. XRD confirmed a hexagonal wurtzite phase with an average crystallite size of 36.44 nm, while UV-vis spectroscopy showed [...] Read more.
Biosynthesized ZnO nanostructures were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), ultraviolet–visible (UV-vis) spectroscopy, and Fourier transform–infrared (FT-IR) spectroscopy. XRD confirmed a hexagonal wurtzite phase with an average crystallite size of 36.44 nm, while UV-vis spectroscopy showed a distinct absorption peak at 321 nm. The Zeta potential of the ZnO nanostructures was −24.28 mV, indicating high stability in suspension, which is essential for their dispersion and functionality in biological and environmental applications. The nematicidal activity of ZnO was evaluated in vitro at concentrations of 150, 300, 450, and 600 ppm, with the highest concentration achieving 75.71% mortality of second-stage juveniles (J2s) after 72 h. The calculated LC50 values for the treatments were 270.33 ppm at 72 h. Additionally, molecular docking studies indicated significant interactions between the ZnO nanostructures and nematode proteins, HSP-90 and ODR1, supporting their potential nematicidal mechanism. This research highlights the effectiveness of neem leaf extract-mediated ZnO nanostructures as an eco-friendly, sustainable alternative for nematode control, presenting a promising solution for agricultural pest management. Full article
(This article belongs to the Special Issue (Bio)nanomaterials in Catalysis)
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19 pages, 12441 KiB  
Article
Mitogenome Characteristics and Intracellular Gene Transfer Analysis of Four Adansonia Species
by Tingting Hu, Fengjuan Zhou, Lisha Wang, Xinwei Hu, Zhongxiang Li, Xinzeng Li, Daoyuan Zhou and Hui Wang
Genes 2025, 16(7), 846; https://doi.org/10.3390/genes16070846 - 21 Jul 2025
Viewed by 276
Abstract
Adansonia L. (1753) belongs to the family Malvaceae and is commonly known as the baobab tree. This species holds significant cultural and ecological value and is often referred to as the ‘tree of life.’ Although its nuclear genome has been reported, the mitogenome [...] Read more.
Adansonia L. (1753) belongs to the family Malvaceae and is commonly known as the baobab tree. This species holds significant cultural and ecological value and is often referred to as the ‘tree of life.’ Although its nuclear genome has been reported, the mitogenome has not yet been studied. Mitogenome research is crucial for understanding the evolution of the entire genome. In this study, we assembled and analyzed the mitogenomes of four Adansonia species by integrating short-read and long-read data. The results showed that the mitogenomes of all four Adansonia species were resolved as single circular sequences. Their total genome lengths ranged from 507,138 to 607,344 bp and contained a large number of repetitive sequences. Despite extensive and complex rearrangements between the mitogenomes of Adansonia and other Malvaceae species, a phylogenetic tree constructed based on protein-coding genes clearly indicated that Adansonia is more closely related to the Bombax. Selection pressure analysis suggests that the rps4 gene in Adansonia may have undergone positive selection compared to other Malvaceae species, indicating that this gene may play a significant role in the evolution of Adansonia. Additionally, by analyzing intracellular gene transfer between the chloroplast, mitochondria, and nuclear genomes, we found that genes from the chloroplast and mitochondria can successfully transfer to each chromosome of the nuclear genome, and the psbJ gene from the chloroplast remains intact in both the mitochondrial and nuclear genomes. This study enriches the genetic information of Adansonia and provides important evidence for evolutionary research in the family Malvaceae. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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