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16 pages, 1121 KiB  
Article
Thromboinflammatory Biomarkers in Lymphomas: Linking Inflammation to Thrombosis Risk
by Emilija Živković, Olivera Mitrović-Ajtić, Tijana Subotički, Jelena Ivanović, Vladimir Otašević, Dragoslava Đikić, Miloš Diklić, Milica Vukotić, Teodora Dragojević, Dejana Stanisavljević, Darko Antić and Vladan P. Čokić
Int. J. Mol. Sci. 2025, 26(5), 2058; https://doi.org/10.3390/ijms26052058 - 26 Feb 2025
Viewed by 9
Abstract
Thrombosis is a critical complication in lymphomas, driven by chronic inflammation. To observe this systemic mechanism, we evaluated inflammatory cytokines, neutrophil and monocyte activation, and platelet function in diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and Hodgkin lymphoma (HL), with and without [...] Read more.
Thrombosis is a critical complication in lymphomas, driven by chronic inflammation. To observe this systemic mechanism, we evaluated inflammatory cytokines, neutrophil and monocyte activation, and platelet function in diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and Hodgkin lymphoma (HL), with and without thrombosis using ELISA and flow cytometry according to laboratory and clinical data. Interleukin-1β was elevated across lymphomas and inversely correlated with the Khorana score for venous thromboembolism, while increased tumor necrosis factor-alpha (TNF-α) was inversely associated with the International Prognostic Index (IPI) in thrombosis-associated lymphomas. Neutrophil activation was increased in DLBCL, while elevated neutrophil extracellular traps (NETs) biomarkers were inversely consistent with thrombosis and the ThroLy score. NETs were elevated in HL. Classical monocytes were increased in all lymphoma subtypes, with intermediate and tissue factor (TF)-carrying monocytes elevated in DLBCL and HL. Platelet activation was pronounced, with platelet–monocyte aggregates and platelet-associated TF elevated in DLBCL and FL but not HL. P-selectin was increased in lymphomas with thrombosis, aligned with Khorana and ThroLy scores, and reflected clinical stage while inversely correlating with IPI in non-thrombotic lymphomas. These findings highlight distinct thromboinflammatory mechanisms across lymphoma subtypes, providing insights into biomarkers for thrombosis risk and therapeutic targets in lymphoma management. Full article
(This article belongs to the Section Molecular Immunology)
19 pages, 5768 KiB  
Article
Weizmannia coagulans BC99: A Novel Adjunct to Protein Supplementation for Enhancing Exercise Endurance and Reducing Fatigue
by Minghan Guo, Lina Zhao, Li Cao, Xuan Li, Jie Zhang, Yao Dong, Ying Wu and Shaobin Gu
Foods 2025, 14(5), 801; https://doi.org/10.3390/foods14050801 (registering DOI) - 26 Feb 2025
Viewed by 82
Abstract
Adequate protein consumption is essential for optimal physical fitness and enhancing athletic performance. This study explored the impact of Weizmannia coagulans BC99 on protein-supplemented male fatigued mice, examining aspects such as protein digestion, exercise endurance, fatigue-related biochemistry, oxidative stress, and gut microbiota alterations. [...] Read more.
Adequate protein consumption is essential for optimal physical fitness and enhancing athletic performance. This study explored the impact of Weizmannia coagulans BC99 on protein-supplemented male fatigued mice, examining aspects such as protein digestion, exercise endurance, fatigue-related biochemistry, oxidative stress, and gut microbiota alterations. Results indicate that the synergistic effect of probiotics and protein significantly boosts the activity of protein-digesting enzymes, enhances protein absorption, and reduces serum levels of urea nitrogen, lactate, lactate dehydrogenase, creatine kinase, malondialdehyde, and the inflammatory cytokines interleukin-1β and interleukin-6 in skeletal muscle. Additionally, serum catalase, glutathione, superoxide dismutase levels, interleukin-4 in skeletal muscle, and glycogen stores in muscle and liver were notably increased. The study also found elevated mRNA expression levels of Nrf2 and HO-1 in skeletal muscle. Furthermore, an increase in short-chain fatty acids was observed in the probiotic treatment group, and 16S rDNA sequencing revealed that Weizmannia coagulans BC99 enhanced gut microbiota diversity and augmented beneficial bacterial populations including Roseburia, Mucispirillum, Rikenella, and Kineothrix. Collectively, these findings suggest that combining BC99 with protein supplementation can effectively improve gut flora, thereby enhancing exercise capacity and exerting potent anti-fatigue effects. Our research provides a new possibility for alleviating exercise-induced fatigue. Full article
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14 pages, 1330 KiB  
Article
Antioxidant-Rich Polyfloral Bee Pollen Exerts Antimicrobial Activity and Anti-Inflammatory Effect in A549 Lung Epithelial Cells by Modulating the NF-κB Pathway
by Andrea Cavallero, Francesca Vidotto, Cristiana Sbrana, Laryssa Peres Fabbri, Giulio Petroni and Morena Gabriele
Foods 2025, 14(5), 802; https://doi.org/10.3390/foods14050802 - 26 Feb 2025
Viewed by 84
Abstract
Bee pollen is produced by honeybees from the agglutination of pollen grains belonging to one or more plant species. Although it is intended to be a nutritional source for the hive, its remarkable concentration of nutrients and phytochemicals, combined with its pleasant organoleptic [...] Read more.
Bee pollen is produced by honeybees from the agglutination of pollen grains belonging to one or more plant species. Although it is intended to be a nutritional source for the hive, its remarkable concentration of nutrients and phytochemicals, combined with its pleasant organoleptic qualities, makes it appealing for human consumption. This study examined the phytochemical content and the antioxidant and antimicrobial activities of a polyfloral bee pollen collected in Tuscany (Italy). Additionally, its less studied anti-inflammatory potential towards tumor necrosis factor-alpha (TNF-α)-inflamed A549 cells was evaluated to assess its possible use in inflammatory respiratory diseases. Bee pollen extract (BPE) was chemically characterized in terms of total polyphenol (20.2 ± 1.5 mg gallic acid equivalents/g fw), flavonoid (9.22 ± 0.64 mg quercetin equivalents/g fw), and carotenoid (10.4 ± 1.4 µg carotenoids/g fw) contents. BPE exerted good antioxidant and antiradical activities in ferric reducing antioxidant power (38.6 ± 4.5 mg Fe2+/g fw), oxygen radical absorbance capacity (433.77 ± 18.95 μmol TE/g fw), and 2,2-diphenyl-1-picrylhydrazyl (EC50 = 613.8 ± 79.2 μg/mL) assays. Additionally, BPE inhibited the growth of Bacillus subtilis and Pseudomonas stutzeri (MIC = 10 mg/mL) in the microdilution assay. When TNF-α-inflamed A549 cells were pretreated with BPE (10 and 50 µg/mL), the upregulated interleukin-8 gene and cyclooxygenase-2 gene and protein expression were significantly attenuated. BPE modulated the nuclear factor-κB signaling pathway by decreasing its active phosphorylated form levels. These encouraging results confirm that honeybee pollen is a valuable health-promoting food that could alleviate the inflammatory component of various chronic pulmonary conditions. Full article
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15 pages, 2047 KiB  
Article
Unraveling the Extra Virgin Olive Oil Effect on Inflammation and on Gut and Saliva Microbiota
by Marta Correia, Ana T. P. C. Gomes, Inês Moreira, Jane El Maghariki, Karina Mendes, Maria José Correia, Rui Barros, Joana Cristina Barbosa, Nuno Rosa and Ana Maria Gomes
Biomolecules 2025, 15(3), 338; https://doi.org/10.3390/biom15030338 (registering DOI) - 26 Feb 2025
Viewed by 121
Abstract
Extra virgin olive oil (EVOO) with a high content of polyphenols has attracted attention due to its proved beneficial effects in decreasing the risk of cardiovascular disease, modulating cholesterol levels (HDL and LDL), modulating inflammatory markers, and decreasing the levels of haemoglobin1Ac, suggesting [...] Read more.
Extra virgin olive oil (EVOO) with a high content of polyphenols has attracted attention due to its proved beneficial effects in decreasing the risk of cardiovascular disease, modulating cholesterol levels (HDL and LDL), modulating inflammatory markers, and decreasing the levels of haemoglobin1Ac, suggesting that EVOO can have an impact in glycemia regulation. This study assessed the impact of the consumption of a northern Portuguese polyphenol-rich EVOO with a high profile of bioactive molecules on several parameters, such as saliva and serum inflammatory biomarkers, and explored EVOO impact on gut and oral microbiota regarding Bacillota and Bacteroidota content. Thus, the impact on glycated haemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP), inflammatory biomarkers, and faecal and salivary microbiomes were evaluated before and after the exposure to EVOO. The results showed that EVOO promotes a decrease in the levels of HbA1C and in the pro-inflammatory interleukin IL-1β, associated with inflammatory processes. Moreover, EVOO intake modulated gut and oral microbiota, increasing Bacteroidota in both ecological niches and Bacillota in the oral microbiota, both phyla being associated with health, demonstrating a prebiotic effect. Full article
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24 pages, 862 KiB  
Article
Changes in Oxidative Stress, Inflammatory Markers, and Lipid Profile After a 6-Week High-Antioxidant-Capacity Dietary Intervention in CVD Patients
by Magdalena Czlapka-Matyasik, Lidia Wadolowska, Paweł Gut and Anna Gramza-Michałowska
Nutrients 2025, 17(5), 806; https://doi.org/10.3390/nu17050806 - 26 Feb 2025
Viewed by 105
Abstract
Background/Objectives: Increased dietary antioxidant capacity is a good means of lowering oxidative stress and cardiovascular risk. Established antioxidant capacity doses should be tested using dietary intervention. Methods: We analysed the influence of a high-antioxidant-capacity diet on oxidative stress (OS) and inflammatory [...] Read more.
Background/Objectives: Increased dietary antioxidant capacity is a good means of lowering oxidative stress and cardiovascular risk. Established antioxidant capacity doses should be tested using dietary intervention. Methods: We analysed the influence of a high-antioxidant-capacity diet on oxidative stress (OS) and inflammatory and lipid profile in CVD (cardiovascular disease) subjects with initially low (LowA) and high (HighA) antioxidant capacity markers. It was an experimental study with a 6-week dietary intervention (DI). Forty-eight CVD patients completed the DI. Blood and urine samples were collected, and anthropometric measurements were taken. Dietary data were collected using a multi-day food record method. α-tocopherol, β-carotene, and retinol were chosen as antioxidant capacity markers; F2-isoprostanes (F2-IsoP), oxidised low-density lipoproteins (oxLDL), and uric acid (UA) were used as OS markers; and interleukin 6 (IL-6) and high-sensitivity C-reactive proteins (hs-CRP) were used as inflammatory markers. Total cholesterol, low- and high-density lipoproteins, and triglycerides (TCHOL, LDL, HDL, TRI) as lipid profiles were analysed. Two groups of subjects with LowA and HighA profiles were identified. Results: The total dietary antioxidant capacity intake during DI was increased by 56%. In the total sample, the DI increased β-carotene, retinol, and UA, and decreased IL-6 oxLDL. The LowA group exhibited increased β-carotene, α-tocopherol, retinol, and decreased IL-6. The HighA group exhibited increased β-carotene and decreased IL-6, F2-IsoP, oxLDL, and oxLDL/LDL ratio. In the HighA group, compared to the LowA group, greater decreases in α-tocopherol and F2-IsoP were found. In both groups, inflammatory markers (IL-6) decreased, and β-carotene increased. Conclusions: The DI results depended on the antioxidant capacity profile at baseline; nevertheless, the established DI including selected antioxidative snacks significantly decrease oxidative stress and improve antioxidant capacity. Further research on diet natural antioxidant supplementation needs to be continued. Full article
(This article belongs to the Section Lipids)
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19 pages, 2329 KiB  
Article
Effects of Deoxynivalenol Detoxifier on Growth Performance, Blood Biochemical Indices, and Microbiota Composition of Piglets
by Luyao Zhang, Yongwei Wang, Weiwei Wang, Li Wang, Jingjing Shi, Junlin Cheng, Jing Zhang, Aike Li, Beibei He and Zhiyong Fan
Int. J. Mol. Sci. 2025, 26(5), 2045; https://doi.org/10.3390/ijms26052045 - 26 Feb 2025
Viewed by 64
Abstract
Deoxynivalenol (DON), also known as vomitoxin, has a high detection and exceeding rate in feed and is prone to causing symptoms such as loss of appetite, weight loss, vomiting, and diarrhoea in animals, which brings great harm to the aquaculture industry. The common [...] Read more.
Deoxynivalenol (DON), also known as vomitoxin, has a high detection and exceeding rate in feed and is prone to causing symptoms such as loss of appetite, weight loss, vomiting, and diarrhoea in animals, which brings great harm to the aquaculture industry. The common mycotoxin adsorbents have low adsorption rates for DON, and the use of biological methods to remove DON in feeds has gradually become a research trend. One hundred and twenty crossbred barrows were randomly divided into four groups, which included the normal diet group (CON), normal diet + detoxifier group (Det), DON-polluted diet group (DON), and DON-polluted diet + DON detoxifier group (DON + Det); the experiment lasted for 28 d. The results showed that, compared with piglets fed a normal diet, those piglets fed DON-polluted diets significantly decreased their average daily gain (ADG) and average daily feed intake (ADFI) during the 1–14 d and 1–28 d periods; the content of immunoglobulin G (IgG), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), interleukin-4 (IL-4), and interleukin-10 (IL-10) in serum was decreased; and the content of aminotransferase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA), diamine oxidase (DAO), and endotoxin (LPS) was increased in pigs fed DON-polluted diets; meanwhile, feeding piglets DON-polluted diets significantly reduced the levels of acetic acid, propionic acid, and total short-chain fatty acids (SCFAs) as well as gut microbiota health index (GMHI) in piglet faeces, but increased the relative abundance of Treponema, Prevotellaceae_UGG-001, Lachnospiraceae_XPB1014_group, Frisingicoccus and Sphaerochaeta. In contrast, the addition of a composite detoxifier effectively ameliorated the reduction in ADG and ADFI in piglets caused by DON-polluted diets. It suppressed the reduction in CAT, SOD, GSH-PX, IL-4, and IL-10 and the elevation of TNF-α, IL-2, IL-6, IL-12, MDA, LPS, and DAO in serum; the composite detoxifier also restrained the decrease in SCFA in piglet faeces and increased the relative abundance of Ruminococcus, Lachnospiraceae_NK4A136_group, Lachnospiraceae_AC2044_group, UCG-009, and Eubacterium_siraeum_group bacteria. The composite detoxifier effectively mitigated the adverse effects of a DON-polluted diet on piglet growth performance, blood biochemical indices, and gut microbiota composition. Full article
(This article belongs to the Section Molecular Microbiology)
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22 pages, 6715 KiB  
Article
Anti-Inflammatory and Antioxidant Effects of White Grape Pomace Polyphenols on Isoproterenol-Induced Myocardial Infarction
by Raluca Maria Pop, Paul-Mihai Boarescu, Corina Ioana Bocsan, Mădălina Luciana Gherman, Veronica Sanda Chedea, Elena-Mihaela Jianu, Ștefan Horia Roșian, Ioana Boarescu, Floricuța Ranga, Liliana Lucia Tomoiagă, Alexandra Doina Sîrbu, Andrei Ungur, Marian Taulescu, Alina Elena Pârvu and Anca Dana Buzoianu
Int. J. Mol. Sci. 2025, 26(5), 2035; https://doi.org/10.3390/ijms26052035 - 26 Feb 2025
Viewed by 115
Abstract
Grape pomace (GP), the residue left after grape pressing in winemaking, is rich in polyphenols, including flavonoids, tannins, and phenolic acids, which have antioxidant and anti-inflammatory properties. The present study aimed to evaluate the cardioprotective effects of white grape pomace (WGP) extract in [...] Read more.
Grape pomace (GP), the residue left after grape pressing in winemaking, is rich in polyphenols, including flavonoids, tannins, and phenolic acids, which have antioxidant and anti-inflammatory properties. The present study aimed to evaluate the cardioprotective effects of white grape pomace (WGP) extract in two concentrations rich in polyphenols (795 mg polyphenols from WGP/kg body weight (bw) and 397.5 mg polyphenols from WGP/kg bw)), on isoproterenol (ISO)-induced myocardial infarction (MI), focusing on its anti-inflammatory and antioxidant effects. White grape pomace administration for 14 days offered a cardio-protective effect and prevented prolongation of the QT and QTc intervals on the electrocardiogram. Both concentrations of WGP prevented the elevation of nitric oxide (NO) and malondialdehyde (MDA) in the serum, with the best results being observed for the highest concentration (p < 0.05). White grape pomace administration offered a reduction in pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin 1β (IL-1β) in both serum and tissue in a dose-dependent manner, with the highest WGP concentration having the best effect (p < 0.05). Moreover, WGP reduced histological changes associated with MI. The findings of the present study demonstrate that WGP extract exerts cardio protective effects by reducing MI-associated inflammation and oxidative stress. Full article
(This article belongs to the Section Bioactives and Nutraceuticals)
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14 pages, 2903 KiB  
Article
Polysome Profiling Proves Impaired IL-10 and Caspase-8 Translation in PBMCs of Hemodialysis Patients
by Amanda Dawood, Roman Fiedler, Silke Markau, Matthias Girndt and Christof Ulrich
Biomolecules 2025, 15(3), 335; https://doi.org/10.3390/biom15030335 - 26 Feb 2025
Viewed by 79
Abstract
Triggered by uremic intoxication, a surplus of inflammatory mediators is present in the serum of hemodialysis (HD) patients. Anti-inflammatory counterbalancing mechanisms initiated by interleukin-10 (IL-10) and caspase-8 (Casp-8) appear to be disturbed. Earlier observations let us suppose that translational rather than transcriptional mechanisms [...] Read more.
Triggered by uremic intoxication, a surplus of inflammatory mediators is present in the serum of hemodialysis (HD) patients. Anti-inflammatory counterbalancing mechanisms initiated by interleukin-10 (IL-10) and caspase-8 (Casp-8) appear to be disturbed. Earlier observations let us suppose that translational rather than transcriptional mechanisms are responsible for this effect. Therefore, we investigated the polysome profiling of isolated PBMCs to study gene-specific mRNAs attached to monosomes and polysomes in HD patients (n = 42), patients with lipid disorder and normal renal function (LD, n = 10) and healthy control subjects (CO, n = 9). CRP (C-reactive protein) as a marker of inflammation was significantly elevated in HD and LD patients compared to CO subjects. NGAL (neutrophil-associated lipocalin), a potential marker of kidney disease and inflammation was increased in HD versus LD and CO. LD patients, however, had significantly higher proteosomal IL-10 and Casp-8 activities. LD and HD are two high cardiovascular risk groups with microinflammation. Lower translational activities of IL-10 and Casp-8 mRNAs in HD may be the result of a weak anti-inflammatory response potentially associated with the uremic immune defect. Full article
(This article belongs to the Special Issue Inflammation and Hemostasis: 2nd Edition)
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14 pages, 1427 KiB  
Systematic Review
Dupilumab, a Potential Novel Treatment for Hailey–Hailey Disease
by Liliana Gabriela Popa, Calin Giurcaneanu, Florentina Zaharia, Andreea Grigoras, Alexandra Denisa Oprea and Cristina Beiu
Clin. Pract. 2025, 15(3), 48; https://doi.org/10.3390/clinpract15030048 - 26 Feb 2025
Viewed by 50
Abstract
Background/Objectives: Hailey–Hailey disease (HHD) is an uncommon genodermatosis with autosomal dominant inheritance caused by loss-of-function mutations in the ATP2C1 gene, which lead to disruption in keratinocyte adhesion and intraepidermal acantholysis. The chronic nature of the disease, its frequent recurrences and the lack of [...] Read more.
Background/Objectives: Hailey–Hailey disease (HHD) is an uncommon genodermatosis with autosomal dominant inheritance caused by loss-of-function mutations in the ATP2C1 gene, which lead to disruption in keratinocyte adhesion and intraepidermal acantholysis. The chronic nature of the disease, its frequent recurrences and the lack of specific treatment pose real challenges in the long-term management of these patients. Recent studies have evaluated the effect of dupilumab, a human monoclonal antibody that blocks interleukin-4 and -13 receptor in refractory HHD, with very promising results. The aim of this study was to review the published data on the use of dupilumab for the treatment of HHD, to present our own experience in the field, and to discuss the mechanisms underlying dupilumab’s beneficial effects in HHD and the future treatment perspectives. Methods: A search of the medical literature on the use of dupilumab in the treatment of HHD was conducted. The terms “Hailey–Hailey disease”, “benign familial pemphigus”, “benign chronic pemphigus”, and “dupilumab” were searched across multiple databases (Medline, Chrocane Library, EMBASE) from inception until 30 September 2024. Results: To date, six manuscripts describing 11 refractory HHD cases treated with dupilumab have been published. All the patients experienced significant clinical improvement. The authors reported sustained disease quiescence in seven patients (64%), monitored for 5 to 24 months. None of the patients experienced adverse effects related to dupilumab. To the existing evidence, we add a new case of recalcitrant HHD successfully treated with dupilumab. Conclusions: Mounting evidence indicates dupilumab as a safe and efficient therapeutic alternative in patients with severe, refractory HHD. However, the long-term efficacy of dupilumab and the optimal therapeutic regimen for HHD are yet to be determined. Full article
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13 pages, 2029 KiB  
Article
Human Recombinant Interleukin-6 and Leukemia Inhibitory Factor Improve Inner Cell Mass Cell Number but Lack Cryoprotective Activities on In Vitro-Produced Bovine Blastocysts
by Mary A. Oliver, Kayla J. Alward, Michelle L. Rhoads and Alan D. Ealy
Animals 2025, 15(5), 668; https://doi.org/10.3390/ani15050668 - 25 Feb 2025
Viewed by 177
Abstract
This work explored whether supplementing recombinant human interleukin-6 (IL6), interleukin-11 (IL11), or leukemia inhibitory factor (LIF) improves IVP bovine embryo development, morphology, and cryosurvivability. Embryos were treated from day 5 to 8 post-fertilization with either the carrier only (control) or 100 ng/mL of [...] Read more.
This work explored whether supplementing recombinant human interleukin-6 (IL6), interleukin-11 (IL11), or leukemia inhibitory factor (LIF) improves IVP bovine embryo development, morphology, and cryosurvivability. Embryos were treated from day 5 to 8 post-fertilization with either the carrier only (control) or 100 ng/mL of IL6, IL11, or LIF. Blastocyst formation and stage were determined on day 7 and 8. A subset of day 8 blastocysts was processed for immunofluorescence to count trophectoderm (TE) and inner cell mass (ICM) cell numbers and another subset was slow frozen and stored in liquid nitrogen until thawing. No differences in the blastocyst rate or blastocyst stage of development were detected. Increases in ICM cell numbers were observed for IL6 and LIF but not the IL11 treatment. None of the cytokine treatments applied before freezing affected post-thaw survival, TE or ICM cell number, or cell death 24 h after thawing. In conclusion, supplementing IL6 and LIF improves ICM cell numbers in non-frozen blastocysts, but there was no evidence that any of these cytokine treatments contain cryoprotective properties in bovine embryos. Full article
(This article belongs to the Special Issue Recent Advances in Reproductive Biotechnologies—Second Edition)
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25 pages, 4398 KiB  
Article
Influence of a Very High-Molecular Weight Fucoidan from Laminaria hyperborea on Age-Related Macular Degeneration-Relevant Pathomechanisms in Ocular Cell Models
by Philipp Dörschmann, Georg Kopplin, Tabea Thalenhorst, Charlotte Seeba, Sadia Fida Ullah, Vaibhav Srivastava, Johann Roider and Alexa Klettner
Mar. Drugs 2025, 23(3), 101; https://doi.org/10.3390/md23030101 - 25 Feb 2025
Viewed by 109
Abstract
Fucoidans from Laminaria hyperborea (LH) can be antioxidative, antiangiogenic, and anti-inflammatory. In this study, a very high-molecular weight (3700 kDa) fucoidan from LH, FucBB04, was tested regarding its bioactivity in age-related macular degeneration (AMD) models in vitro. Primary retinal pigment epithelium (RPE) [...] Read more.
Fucoidans from Laminaria hyperborea (LH) can be antioxidative, antiangiogenic, and anti-inflammatory. In this study, a very high-molecular weight (3700 kDa) fucoidan from LH, FucBB04, was tested regarding its bioactivity in age-related macular degeneration (AMD) models in vitro. Primary retinal pigment epithelium (RPE) from pig eyes, human uveal melanoma cell line OMM-1, and RPE cell line ARPE-19 were used. Substituents of the extract were determined with chemical analysis. Cell viability was tested with tetrazolium assay (MTT), oxidative stress was induced by H2O2 or erastin, respectively. Secreted vascular endothelial growth factor A (VEGF-A) was assessed with ELISA. Retinal pigment epithelium 65 kDa protein (RPE65) and protectin (CD59) protein expression were tested in Western blot. Cell barrier was assessed by measuring trans-epithelial electrical resistance (TEER), phagocytic ability by a fluorescence assay. Gene expression and secretion of interleukin 6 (IL-6) and interleukin 8 (IL-8) were tested in real-time PCR and ELISA. FucBB04 displayed no oxidative stress protective effects. Its effect on VEGF was inconsistent, with VEGF secretion reduced in primary RPE, but not in ARPE-19. On the other hand, Lipopolysaccharide (LPS) and polyinosinic/polycytidylic acid (PIC)-induced IL-6 or IL-8 secretion was reduced by FucBB04, while complement inhibiting protein CD59 was not affected. In addition, FucBB04 did not influence the gene expression of IL-6 or IL-8. Visual cycle protein RPE65 expression, phagocytic ability, and barrier function were reduced by FucBB04. Very high-molecular weight fucoidan from LH shows bioactivities against AMD-related pathological pathways, but adverse effects on RPE function may limit its suitability as a therapeutic compound. Smaller high-molecular weight fucoidans are recommended for further research. Full article
(This article belongs to the Special Issue Marine Anti-Inflammatory and Antioxidant Agents, 4th Edition)
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26 pages, 1224 KiB  
Systematic Review
Unveiling the Molecular Crosstalk Between Periodontal and Cardiovascular Diseases: A Systematic Review
by Gunaraj Dhungana, Dollada Srisai, Chethan Sampath, Jeremiah Soliman, Regan M. Kelly, Honar Y. Saleh, Abdelrahman Sedik, Edilberto Raynes, Alexys Ferguson, Leela Subhashini Choudary Alluri and Pandu R. Gangula
Dent. J. 2025, 13(3), 98; https://doi.org/10.3390/dj13030098 - 25 Feb 2025
Viewed by 265
Abstract
Background/Objectives: Periodontal disease (PD) is a chronic inflammatory condition caused by dysbiosis of the oral microbiome. PD is linked to systemic inflammation and endothelial dysfunction, which associate it with cardiovascular disease (CVD). This systematic review explores the molecular and microbial mechanisms through which [...] Read more.
Background/Objectives: Periodontal disease (PD) is a chronic inflammatory condition caused by dysbiosis of the oral microbiome. PD is linked to systemic inflammation and endothelial dysfunction, which associate it with cardiovascular disease (CVD). This systematic review explores the molecular and microbial mechanisms through which periodontal pathogens, including “Red Complex” bacteria (Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola) and Fusobacterium nucleatum, influence cardiovascular health via inflammatory pathways, immune modulation, and microbial dissemination. Methods: A systematic review was conducted following PRISMA guidelines. A literature search was conducted in the PubMed and ScienceDirect databases using relevant keywords, with strict inclusion and exclusion criteria, from the first week of September 2024 to the first week of October 2024. Studies addressing the relationship between PD and CVD were assessed for methodological rigor, relevance, and data availability. The outcomes were synthesized using a descriptive narrative approach. Out of 591 records screened, 421 full-text articles were sought for retrieval. The final review included 58 articles providing supplementary aggregated data after eligibility assessment. Results: The pathogenesis of PD involves the activation of immune cells and the release of pro-inflammatory cytokines (such as IL-1, IL-6, TNF-α, and PGE2) and chemokines (including IL-8 and MCP-1) along with oxidative stress driven by reactive oxygen species (ROS). Periodontal pathogens trigger endothelial oxidative stress and systemic inflammation via Toll-like receptors (TLRs), NF-κB signaling, and nitric oxide (NO) dysregulation, contributing to endothelial dysfunction and atherogenesis. Biomarkers, such as C-reactive protein, interleukins, and matrix metalloproteinases (MMPs), further highlight the systemic inflammatory response. Conclusions: This review underscores the significant role of periodontal pathogens and inflammatory mediators in systemic health, particularly in the progression of CVD. Although existing evidence illustrates these associations, the underlying molecular mechanisms remain inadequately understood, indicating a need for further research to advance precision medicine and therapeutic strategies. Full article
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14 pages, 2147 KiB  
Article
Naringenin’s Neuroprotective Effect on Diazino-Induced Cerebellar Damage in Male Albino Rats, with Modulation of Acetylcholinesterase
by Abdullah A. Saati
Brain Sci. 2025, 15(3), 242; https://doi.org/10.3390/brainsci15030242 - 25 Feb 2025
Viewed by 129
Abstract
Background: Diazinon, a well-known organophosphorus compound, is recognized for its neurotoxic effects, primarily through the inhibition of acetylcholinesterase (AChE) and induction of oxidative stress. Aim: This study evaluates the neuroprotective effects of naringenin, a citrus flavonoid, against diazinon-induced cerebellar damage in male albino [...] Read more.
Background: Diazinon, a well-known organophosphorus compound, is recognized for its neurotoxic effects, primarily through the inhibition of acetylcholinesterase (AChE) and induction of oxidative stress. Aim: This study evaluates the neuroprotective effects of naringenin, a citrus flavonoid, against diazinon-induced cerebellar damage in male albino rats. Materials and methods: Twenty-four rats were divided into four groups: control, naringenin, diazinon, and diazinon with naringenin. Results: Histological examination revealed altered structures of Purkinje cells in the cerebellum of the diazinon group. Naringenin co-treatment significantly improved cerebellar histology and modulated oxidative stress markers by decreasing malondialdehyde (MDA) and increasing glutathione (GSH) and glutathione peroxidase (GPx) levels. Additionally, naringenin exhibited anti-inflammatory effects by decreasing nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) levels, while increasing interleukin-10 (IL-10). It also reduced apoptotic markers, including p53, Bax, caspase-9, caspase-8, and caspase-3, while increasing the anti-apoptotic marker Bcl-2. Furthermore, naringenin modulated AChE activity, leading to decreased acetylcholine levels and reduced neurotoxicity. Conclusions: These findings suggest that naringenin’s antioxidant, anti-inflammatory, and anti-apoptotic properties contribute to its neuroprotective role against diazinon-induced cerebellar damage. Full article
(This article belongs to the Section Neuropharmacology and Neuropathology)
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20 pages, 13655 KiB  
Article
Transcriptome Profiling Reveals That the African Swine Fever Virus C315R Exploits the IL-6 STAT3 Signaling Axis to Facilitate Virus Replication
by Shuxian Geng, Zhonghui Zhang, Jie Fan, Hualin Sun, Jifei Yang, Jianxun Luo, Guiquan Guan, Hong Yin, Qiaoying Zeng and Qingli Niu
Viruses 2025, 17(3), 309; https://doi.org/10.3390/v17030309 - 24 Feb 2025
Viewed by 108
Abstract
African swine fever (ASF) is an acute and highly contagious disease that has caused great losses in the past years. It is caused by African swine fever virus (ASFV), which is a large DNA virus encoding about 165 genes. It has been shown [...] Read more.
African swine fever (ASF) is an acute and highly contagious disease that has caused great losses in the past years. It is caused by African swine fever virus (ASFV), which is a large DNA virus encoding about 165 genes. It has been shown that the purified extracellular ASFV is internalized by both constitutive macropinocytosis and clathrin-mediated endocytosis, and the virus utilizes apoptotic bodies for infection and cell cell transmission. The ASFV-encoded RNA polymerase subunit C315R is thought to play an important role in ASFV replication and transcription. However, its involvement in ASFV infection, particularly in host response, remains only partially understood. In this study, the role of C315R in enhancing ASFV replication was investigated through RNA-Seq transcriptomic analysis, which was based on 3D4/21 cells transfected the plasmid expressing HA-tagged C315R or the empty vector. Our findings revealed that C315R significantly upregulates the expression of inflammatory mediators with a particular emphasis on IL-6. The most differentially expressed genes (DEGs) were predominantly associated with the TNF, IL-17, MAPK, and JAK STAT signaling pathways. RNA-seq results were validated through RT-PCR. Subsequently, we observed that ASFV infection increases IL-6 expression and STAT3 phosphorylation, which is regulated by the ASFV C315R protein. Notably, inhibiting STAT3 phosphorylation with specific inhibitors suppressed ASFV replication. In conclusion, our study demonstrates that the ASFV C315R protein actives STAT3 phosphorylation through promoting the transcription of IL-6 to facilitate virus replication. These findings highlight C315R as a positive regulator in the IL-6 STAT3 signaling axis during ASFV infection. Full article
(This article belongs to the Section Animal Viruses)
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13 pages, 1690 KiB  
Article
Schaftoside Reduces Depression- and Anxiogenic-like Behaviors in Mice Depression Models
by Yue Hu, Yaoxue Gan, Jia Lei, Jinhui Cai, Yecheng Zhou, Hao Chen, Qian Zhang and Yan Shi
Brain Sci. 2025, 15(3), 238; https://doi.org/10.3390/brainsci15030238 - 24 Feb 2025
Viewed by 90
Abstract
Background: Major depressive disorder is a common mental health issue characterized by persistently low mood and high morbidity and mortality. The major pathophysiology is neuroinflammation, as evidenced by elevated cytokine levels. Patients often fail to achieve full remission with the use of currently [...] Read more.
Background: Major depressive disorder is a common mental health issue characterized by persistently low mood and high morbidity and mortality. The major pathophysiology is neuroinflammation, as evidenced by elevated cytokine levels. Patients often fail to achieve full remission with the use of currently available antidepressants, prompting the search for new treatment options. Schaftoside (SS), a flavonoid found in traditional Chinese herbs, has both antioxidant and anti-inflammatory properties. However, its antidepressant effects are poorly understood. Methods: Male C57BL/6 mice underwent chronic unpredictable mild stress (CUMS) and lipopolysaccharide (LPS) treatment to induce depression- and anxiety-like behaviors. SS was administered at 40, 80, and 160 mg/kg for 28 days. The effect on depression-like behaviors was assessed using behavioral assays, and ELISA was used to measure pro-inflammatory cytokines in the serum and hippocampus. Results: SS significantly decreased immobility in the forced swim and tail suspension tests, increased sucrose preference in the sucrose preference test, and reduced feeding latency in the novelty-suppressed feeding test. These findings indicate improved depression and anxiety-like behaviors. ELISA showed that SS lowered interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha levels in the serum and hippocampus of CUMS mice. Conclusions: Our study indicates that SS has antidepressant and anxiolytic effects, possibly through neuroinflammatory processes, making it a promising therapeutic candidate for depression, and thus deserves further investigation into its mechanisms and clinical efficacy. Full article
(This article belongs to the Section Neuropsychiatry)
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