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19 pages, 4696 KB  
Article
PEG-Dependent Tunable Degradation and Curcumin Release from Curcumin-Based Biomedical Polyurethanes
by Man Wang, Hongying Liu, Wei Zhao, Huafen Wang, Yuwei Zhuang, Ran Zhang, Zhaohui Liu, Nengwen Ke and Sichong Chen
Biomolecules 2026, 16(5), 640; https://doi.org/10.3390/biom16050640 (registering DOI) - 24 Apr 2026
Abstract
Curcumin, a plant-derived polyphenolic compound, exhibits diverse pharmacological activities such as antioxidant, anti-inflammatory, anticancer, neuroprotective, and cardiovascular protective effects, and is widely used in food, medicine, and other fields. However, its poor water solubility and easy oxidative degradation limit its extensive application in [...] Read more.
Curcumin, a plant-derived polyphenolic compound, exhibits diverse pharmacological activities such as antioxidant, anti-inflammatory, anticancer, neuroprotective, and cardiovascular protective effects, and is widely used in food, medicine, and other fields. However, its poor water solubility and easy oxidative degradation limit its extensive application in biomedicine. To solve these problems, a series of biomedical polyurethanes (Cur-PU) with similar molecular weights but different PEG contents were successfully synthesized using HO-PCL-OH and HO-PEG-OH as soft segments and curcumin as a chain extender. The results indicated that increasing the PEG content reduced the T1m, T1c, and H1c of Cur-PU, along with a slower crystallization rate and lower crystallinity. More importantly, a higher PEG content decreased the water contact angle but increased water solubility and water uptake, which, combined with reduced crystallinity, enhanced hydrophilicity, swelling ratio, curcumin release rate, and degradation rate in an enzymatic solution and pH 8.0 buffer. Thus, precise regulation of Cur-PU’s degradation and curcumin release was achieved by controlling the PEG content. Biocompatibility tests confirmed that Cur-PU exhibited excellent antioxidant and antibacterial activities, making it a highly promising biomedical material. Full article
(This article belongs to the Section Bio-Engineered Materials)
34 pages, 2767 KB  
Review
Nutraceutical Potential of Fermented Foods: A Perspective on Health and Wellness
by Khalida Shahni, Banaraj Haobam, Oinam Ibochouba Singh, Keisham Shanta Devi, Soibam Thoithoisana Devi, Nanaocha Sharma and Kshetrimayum Birla Singh
Fermentation 2026, 12(5), 211; https://doi.org/10.3390/fermentation12050211 (registering DOI) - 24 Apr 2026
Abstract
Fermented foods hold a significant position in global culinary traditions, particularly within ethnic and traditional diets. They are widely consumed for their distinctive flavors, textures, and health-promoting attributes. Although extensive research exists on fermentation processes, comprehensive insights into the nutraceutical potential and mechanistic [...] Read more.
Fermented foods hold a significant position in global culinary traditions, particularly within ethnic and traditional diets. They are widely consumed for their distinctive flavors, textures, and health-promoting attributes. Although extensive research exists on fermentation processes, comprehensive insights into the nutraceutical potential and mechanistic health benefits of these foods remain limited. This review highlights key fermented products traditionally consumed in the north-eastern region of India including Hawaijar, Soibum, Ngari, alongside global counterparts such as Natto, Chongkukjang, Miso, Kefir, Tempeh, Kimchi, Kombucha, and Sauerkraut. These foods are rich in bioactive compounds (phenolics, peptides, organic acids, and exopolysaccharides), probiotic microorganisms, and essential nutrients that collectively contribute to their antioxidant, anti-inflammatory, antidiabetic, and cardioprotective effects. Recent in vitro and in vivo studies demonstrate that regular consumption of such foods may support the prevention and management of chronic conditions, including diabetes, cardiovascular diseases, obesity, gastrointestinal disorders, and neurodegenerative diseases. However, mechanistic studies remain insufficient to fully elucidate the synergistic interactions between microbial metabolites, host metabolism, and gut microbiota modulation. The review therefore emphasizes the biochemical and therapeutic mechanisms underlying ethnic fermented foods, advocating for advanced metabolomic and molecular approaches to validate their health-promoting efficacy. This review provides a timely and integrative perspective by critically evaluating preclinical and clinical evidence, highlighting mechanistic insights, translational gaps, and future research priorities. These insights will support the development of functional food formulations and reinforce the integration of traditional fermented foods into modern dietary strategies for disease prevention and overall well-being. Full article
(This article belongs to the Special Issue Advances in Fermented Foods and Beverages)
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15 pages, 728 KB  
Article
Picropodophyllotoxin Mitigates Severe Inflammation Through HMGB1 Inhibition
by Gyuri Han, Ga Eun Kim and Jong-Sup Bae
Biomolecules 2026, 16(5), 638; https://doi.org/10.3390/biom16050638 (registering DOI) - 24 Apr 2026
Abstract
Background/Objectives: Plant-derived phytochemicals are being increasingly explored for their ability to treat various illnesses, especially those affecting the vasculature. High mobility group box 1 (HMGB1) acts as a crucial mediator during the late phase of sepsis, promoting the secretion of pro-inflammatory cytokines and [...] Read more.
Background/Objectives: Plant-derived phytochemicals are being increasingly explored for their ability to treat various illnesses, especially those affecting the vasculature. High mobility group box 1 (HMGB1) acts as a crucial mediator during the late phase of sepsis, promoting the secretion of pro-inflammatory cytokines and thereby fueling inflammation and systemic complications. Higher plasma HMGB1 levels not only hinder accurate diagnosis and prognosis but also worsen disease outcomes in inflammatory states. Picropodophyllotoxin (PPT), a key bioactive ingredient isolated from the root of Podophyllum hexandrum, has shown a range of beneficial effects, including anti-cancer and anti-proliferative actions, across several tumor types. Nevertheless, its possible involvement in HMGB1-driven severe vascular inflammation remains unexplored. The current work aimed to investigate whether PPT could influence lipopolysaccharide (LPS)-induced HMGB1 activity and its related inflammatory signaling in human umbilical vein endothelial cells (HUVECs). Methods: A combination of in vitro and in vivo approaches was used to assess the anti-inflammatory action of PPT. These included measurements of endothelial barrier function, cell survival, leukocyte attachment and migration, levels of cell adhesion molecules, and the release of pro-inflammatory factors. Both cultured human endothelial cells and mouse disease models were used to thoroughly evaluate how PPT affects HMGB1-triggered inflammatory reactions. Results: The findings showed that PPT markedly reduced HMGB1 movement from inside HUVECs to the outside, thereby limiting its release into the environment. Moreover, PPT effectively decreased neutrophil sticking and migration, lowered the appearance of HMGB1 receptors, and prevented the activation of nuclear factor-κB (NF-κB), a master switch in inflammatory signaling. At the same time, PPT treatment strongly lowered tumor necrosis factor-α (TNF-α) production, adding to its anti-inflammatory profile. Conclusions: Taken together, these results indicate that PPT potently inhibits HMGB1-driven inflammatory processes by acting at several levels of the inflammatory cascade, such as HMGB1 movement, receptor binding, NF-κB activation, and subsequent cytokine release. Therefore, PPT stands out as a hopeful therapeutic option for HMGB1-related inflammatory diseases and deserves further exploration in preclinical and clinical studies. Full article
(This article belongs to the Section Cellular Biochemistry)
25 pages, 981 KB  
Review
Integrative Therapies in Wound Healing in Small Animals: An Approach Beyond Traditional Medicine
by Jorge Kauã Vila Real Sampaio Santos, Esther Daniela de Sousa Costa, César Carneiro Linhares Fernandes, Annice Aquino Cortez, Arícia Débora Vasconcelos Fonsêca, Rodrigo Fonseca de Medeiros Guedes and Paulo Ricardo Monteiro Araújo
Vet. Sci. 2026, 13(5), 418; https://doi.org/10.3390/vetsci13050418 - 24 Apr 2026
Abstract
The skin represents the largest organ in the body and functions to protect internal tissues from damage and infection. When wounds in small animals do not receive proper management, they may progress to chronic conditions, resulting in pain, delayed healing, and impaired well-being. [...] Read more.
The skin represents the largest organ in the body and functions to protect internal tissues from damage and infection. When wounds in small animals do not receive proper management, they may progress to chronic conditions, resulting in pain, delayed healing, and impaired well-being. Although conventional treatment mainly includes the use of topical antimicrobial agents and anti-inflammatory drugs, integrative veterinary medicine has been considered a promising complementary approach to enhance tissue repair. In this context, this study aimed to review non-conventional therapies applied to wound management in small animals, focusing on ozone therapy, light therapy that stimulates cellular activity, herbal medicine, and apitherapy, especially propolis. Overall, the analyzed studies indicate that ozone may contribute to microbial control and modulation of the immune response; light therapy may stimulate cellular activity and collagen production, promoting healing; medicinal plants present antioxidant and anti-inflammatory effects; and propolis demonstrates antimicrobial and regenerative properties. Thus, when responsibly applied and supported by scientific evidence, these approaches may complement conventional therapy, broaden clinical possibilities, and contribute to improved recovery and quality of life in animals. Full article
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43 pages, 1928 KB  
Review
Hesperidin: A Multifunctional Flavonoid with Therapeutic Potential in the Management of Pathogenesis
by Arshad Husain Rahmani, Fahad M. Alshabrmi, Hajed Obaid A. Alharbi, Amjad Ali Khan, Fahad A. Alhumaydhi and Ahmad Almatroudi
Int. J. Mol. Sci. 2026, 27(9), 3806; https://doi.org/10.3390/ijms27093806 - 24 Apr 2026
Abstract
Hesperidin, a flavonoid abundantly found in citrus fruits, has demonstrated a substantial role in the management of various pathogeneses. Furthermore, the wide range of health-promoting properties of hesperidin, including antioxidant, anti-inflammatory, anti-cancerous, hepatoprotective, neuroprotective, nephroprotective, and cardioprotective effects, has been well documented. Additionally, [...] Read more.
Hesperidin, a flavonoid abundantly found in citrus fruits, has demonstrated a substantial role in the management of various pathogeneses. Furthermore, the wide range of health-promoting properties of hesperidin, including antioxidant, anti-inflammatory, anti-cancerous, hepatoprotective, neuroprotective, nephroprotective, and cardioprotective effects, has been well documented. Additionally, persuasive evidence from both in vivo and in vitro studies highlights its substantial roles in combating obesity, protecting the kidneys, liver, and lung tissue architecture, promoting wound healing, and modulating immune responses. This flavonoid acts as an effective antimicrobial agent against a wide range of microorganisms by inhibiting biofilm formation and disrupting the cell membrane. This review aims to deliver comprehensive insights into the therapeutic potential of hesperidin across different pathogenesis through distinct mechanisms. Moreover, it provides up-to-date evidence on the synergistic properties of this compound with other drugs as well as compounds, and emerging plans to enhance its efficiency in health management through various nanoformulation approaches. Despite its considerable therapeutic potential, the clinical application of hesperidin remains constrained by poor bioavailability, rapid degradation, and dosage-related limitations. Addressing these challenges will require extensive further research to clarify its mechanisms of action, safety profile, and therapeutic efficacy in managing underlying pathogenic conditions. Full article
(This article belongs to the Special Issue New Advances in Bioactive Compounds in Health and Disease)
14 pages, 2488 KB  
Article
Exploratory Changes in Surfactant Protein D During Intermittent Hypoxia and Modulation by Galectin-3 Inhibition
by Saad Al-Anazi, Yasser A. Alshawakir, Syed Shahid Habib, Hayam Gad, Asma F. Alotaibi, Alanoud T. Aljasham, Wajd Ahmed Althakfi, Mohamed A. Mekhtiche and Abeer Abdulmoati Al-Masri
Adv. Respir. Med. 2026, 94(3), 27; https://doi.org/10.3390/arm94030027 - 24 Apr 2026
Abstract
Background: Surfactant Protein D (SP-D) is a critical immunomodulatory collectin maintaining alveolar homeostasis. Obstructive sleep apnea (OSA)-related intermittent hypoxia (IH) disrupts pulmonary surfactant integrity; however, severity-dependent SP-D dynamics remain incompletely characterized. This study explores SP-D as a potential indicator of IH-induced alveolar stress [...] Read more.
Background: Surfactant Protein D (SP-D) is a critical immunomodulatory collectin maintaining alveolar homeostasis. Obstructive sleep apnea (OSA)-related intermittent hypoxia (IH) disrupts pulmonary surfactant integrity; however, severity-dependent SP-D dynamics remain incompletely characterized. This study explores SP-D as a potential indicator of IH-induced alveolar stress and evaluates whether Galectin-3 (Gal-3) inhibition modulates surfactant homeostasis. Methods: Forty adult male Sprague-Dawley rats (8 per group) were randomized to Control (normoxia), Moderate IH (MIH; 15–30 events/hour), Severe IH (SIH; 30–60 events/hour), MIH + Gal-3 inhibitor (Modified Citrus Pectin, 800 mg/kg/day), or SIH + Gal-3 inhibitor. IH exposure lasted 8 h/day for 10 days. Outcomes included circulating SP-D, Surfactant Protein B (SP-B), inflammatory markers, physiological parameters, and histopathological lung injury scores assessed via American Thoracic Society guidelines. Results: SP-D levels showed numerical reductions with increasing IH severity (Control: 1969.07 pg/mL [IQR: 262.15]; SIH: 1404.30 pg/mL [IQR: 351.88]), representing a 28.6% decrease. However, between-group variability resulted in non-significant omnibus testing (Kruskal–Wallis p = 0.187). Gal-3 inhibition elevated SP-D levels, particularly in severe IH (2133.95 pg/mL [IQR: 1240.70]), though high inter-individual variability was observed (CV = 58.1%). SP-B showed significant suppression under moderate IH (p = 0.019) with restoration by treatment. Exploratory correlation analysis revealed moderate positive associations between SP-D and heart rate (r = 0.587) and respiratory rate (r = 0.419) in severe IH, though these did not reach statistical significance (p = 0.126 and p = 0.301, respectively). Histologically, severe IH induced diffuse alveolar damage (total lung score: 19.67 ± 0.82). Gal-3 inhibition produced context-dependent effects: protective in severe IH but paradoxically exacerbating inflammation under moderate IH (29.20 ± 4.64 vs. 20.00 ± 4.34; p < 0.05). Gal-3 inhibition significantly attenuated cardiac injury (injury score: 0.00 ± 0.00 vs. 7.17 ± 0.75 in severe IH; p < 0.001, η2 = 0.859). Conclusions: SP-D demonstrates severity-associated alterations consistent with alveolar epithelial stress during IH, though high variability limits definitive biomarker validation in this sample. Gal-3 inhibition modulates surfactant homeostasis and attenuates cardiopulmonary injury in a context-dependent manner. These findings support further investigation into SP-D as a component of multimodal severity stratification in OSA and highlight Gal-3 inhibition as a context-dependent anti-inflammatory strategy, pending validation in larger cohorts with tissue-level confirmation. Full article
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23 pages, 2311 KB  
Article
Structural Characterization of an Acidic Polysaccharide from Walnut Green Husks and Its Therapeutic Potential in DSS-Induced Ulcerative Colitis
by Sanawar Mansur, Xin Hu, Xinyu Song, Nuerbiye Jueraiti, Anargvl Mahmut, Fuxiang Luo, Aytursun Abuduwaili, Weihao Wang, Zulfiye Talat and Xieraili Tuerxun
Nutrients 2026, 18(9), 1351; https://doi.org/10.3390/nu18091351 - 24 Apr 2026
Abstract
Background/Objectives: The worldwide occurrence of ulcerative colitis (UC) is increasing, but existing treatments frequently suffer from limited effectiveness and notable side effects. walnut green husk polysaccharide (WGHP) has been shown to exhibit anti-inflammatory and immunomodulatory activities; however, its specific potential and mechanisms of [...] Read more.
Background/Objectives: The worldwide occurrence of ulcerative colitis (UC) is increasing, but existing treatments frequently suffer from limited effectiveness and notable side effects. walnut green husk polysaccharide (WGHP) has been shown to exhibit anti-inflammatory and immunomodulatory activities; however, its specific potential and mechanisms of action against colitis remain unclear. This study aimed to evaluate the effectiveness of purified WGHP on (dextran sulfate sodium) DSS-induced UC and elucidate the underlying mechanisms. Methods: WGHP-2-2, a primary acidic polysaccharide fraction, was extracted from crude WGHP and analyzed through chromatography and spectroscopy. The therapeutic efficacy of WGHP-2 was assessed using a murine model of DSS-induced UC. Assessments included disease severity (DAI, colon length, histopathology), inflammatory markers (tissue IL-6, TNF-α, IL-10), and intestinal barrier integrity (Claudin-5, Occludin, ZO-1). Results: WGHP-2-2 is an acidic polysaccharide with a molecular weight of 15.29 kDa. Its composition includes glucosamine, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, and arabinose, with respective molar ratios of 0.55, 8.48, 3.06, 65.99, 4.49, 10.86, and 6.57. Methylation and NMR analyses revealed a backbone mainly composed of →4)-α-D-GalpA-(1→ and →2)-α-D-Rhap-(1→ linkages, with side chains or terminal residues such as T-Rhap, T-Galp, T-Glcp, and T-Araf. In vivo, WGHP-2 significantly mitigated DSS-induced UC symptoms in a dose-dependent manner. Specifically, the high-dose group (123 mg/kg) markedly attenuated colon shortening and improved histological architecture, including the restoration of colonic crypts. WGHP-2 effectively reduced pro-inflammatory cytokines IL-6 and TNF-α in colon tissues, while increasing the anti-inflammatory cytokine IL-10. Conclusions: WGHP-2 mitigates DSS-induced UC by inhibiting pro-inflammatory cytokines (IL-6, TNF-α), increasing IL-10 levels, and improving intestinal barrier integrity through the upregulation of tight junction proteins. These results position WGHP-2 as a promising lead compound for developing functional foods for UC. Full article
(This article belongs to the Section Carbohydrates)
25 pages, 6071 KB  
Article
Paeoniflorin Ameliorates Cecal Ligation and Puncture-Induced Acute Lung Injury in Mice by Modulating Oxidative Stress, Apoptosis, and Inflammation: Shedding Light on the Role of the JAK2/STAT3 Pathway
by Nourhan Hisham Shady, Reham H. Mohyeldin, Nehad M. Reda Abdel Maqsoud, Peter A. Sidhom, Mahmoud A. A. Ibrahim, Ahmed M. Shawky, Mohamed Hisham, Gerhard Bringmann, Usama Ramadan Abdelmohsen and Dalia H. Abu-Baih
Pharmaceuticals 2026, 19(5), 666; https://doi.org/10.3390/ph19050666 (registering DOI) - 24 Apr 2026
Abstract
Background: Acute lung injury (ALI) is a major complication of sepsis, driven by oxidative stress, inflammation, and apoptosis. Paeoniflorin, a monoterpenoid glycoside, has demonstrated notable antioxidant and anti-inflammatory properties, suggesting potential therapeutic value in ALI. Methods: Sepsis-induced ALI was established in mice using [...] Read more.
Background: Acute lung injury (ALI) is a major complication of sepsis, driven by oxidative stress, inflammation, and apoptosis. Paeoniflorin, a monoterpenoid glycoside, has demonstrated notable antioxidant and anti-inflammatory properties, suggesting potential therapeutic value in ALI. Methods: Sepsis-induced ALI was established in mice using the cecal ligation and puncture (CLP) model. The protective effects of paeoniflorin were evaluated by measuring oxidative stress markers (SOD, GSH, and MDA) and pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) using biochemical assays and RT-PCR. Histopathological examination and apoptosis assessment (Bax and Bcl-2 expression) were performed. Western blot analysis was conducted to investigate the involvement of the JAK2/STAT3 signaling pathway. Network pharmacology analysis was used to identify potential molecular targets, and molecular docking was performed to explore binding interactions. Results: CLP-induced ALI resulted in increased oxidative stress and inflammatory responses, as evidenced by elevated MDA and cytokine levels, along with reduced SOD and GSH levels. Paeoniflorin treatment significantly ameliorated these alterations. Histological damage and apoptosis were markedly reduced, accompanied by the downregulation of Bax and upregulation of Bcl-2. Additionally, paeoniflorin inhibited activation of the JAK2/STAT3 pathway. Network pharmacology identified key ALI-related targets, including IL6, TNF, IL1B, HIF1A, STAT3, NFKB1, CCL2, CYBB, CXCL8, and NOX4. Molecular docking revealed strong binding affinity of paeoniflorin toward HIF-1 and JUN, and moderate interactions with IL-1β, TNF-α, and Bax. Conclusions: Paeoniflorin exerts protective effects against sepsis-induced ALI by attenuating oxidative stress, inflammation, and apoptosis, partly through inhibition of the JAK2/STAT3 signaling pathway. These findings highlight its potential as a promising therapeutic candidate for ALI management. Full article
(This article belongs to the Section Natural Products)
21 pages, 1472 KB  
Article
Nostoc commune Extract Attenuates Oxidative Stress and Neuroinflammation in Ischemic Optic Neuropathy Through PI3K/AKT/mTOR Signaling
by Jia-Ying Chien, Wei-Hsun Chan, Mei-Ling Peng, Siu-Fung Chau, Hsien-Yang Tsai, Shi-Huang Lee, Yu-Chen Chen, Wai-Man Cheang and Shun-Ping Huang
Antioxidants 2026, 15(5), 541; https://doi.org/10.3390/antiox15050541 (registering DOI) - 24 Apr 2026
Abstract
Non-arteritic anterior ischemic optic neuropathy (NAION) is a leading cause of sudden vision loss, yet no effective therapy exists to preserve retinal ganglion cells (RGCs) after ischemic injury. Nostoc commune (NC), an edible cyanobacterium with established antioxidant and anti-inflammatory activities, has emerged as [...] Read more.
Non-arteritic anterior ischemic optic neuropathy (NAION) is a leading cause of sudden vision loss, yet no effective therapy exists to preserve retinal ganglion cells (RGCs) after ischemic injury. Nostoc commune (NC), an edible cyanobacterium with established antioxidant and anti-inflammatory activities, has emerged as a potential functional bioresource with relevance to ocular health. Here, we investigated the therapeutic effects of a crude aqueous extract of NC using a rodent model of anterior ischemic optic neuropathy (rAION). NC treatment significantly improved RGC survival, reduced apoptosis, attenuated macrophage and microglial activation (ED-1, Iba1), suppressed proinflammatory cytokine expression (IL-6), enhanced the reparative marker Ym1+2, and preserved optic-nerve myelination. Functionally, NC administration restored visual signaling as demonstrated by improved Flash Visual Evoked Potential amplitudes. Immunoblot analysis showed increased phosphorylation of PI3K/AKT/mTOR/p70S6K signaling components in retinal tissue following NC treatment. Proteomic profiling further demonstrated that NC extract comprises a coordinated repertoire of phycobiliproteins, antioxidant enzymes, and stress-response proteins that may collectively contribute to its biological effects. Together, these findings suggest that Nostoc commune extract may serve as a promising functional food-derived candidate for protecting RGCs and preserving visual function following ischemic optic neuropathy. Further studies are required to identify its active constituents, optimize formulation strategies, and evaluate its translational potential. Full article
34 pages, 1608 KB  
Article
Complementary and Synergistic Effects of Dietary Bacillus subtilis natto and Lactobacillus plantarum on Growth, Immunity and Intestinal Microflora Restructuring in Juvenile Japanese Flounder (Paralichthys olivaceus)
by Yukun Zhang, Manabu Ishikawa, Shunsuke Koshio, Saichiro Yokoyama, Na Jiang, Weilong Wang, Jiayi Chen, Noman Waheed and Xiaoxiao Zhang
Fishes 2026, 11(5), 259; https://doi.org/10.3390/fishes11050259 - 24 Apr 2026
Abstract
Prophylactic antibiotic use in intensive aquaculture promotes antimicrobial resistance, necessitating the development of microbial-based interventions. This study evaluated the individual, complementary, and synergistic effects of Bacillus subtilis natto (BSN) and Lactobacillus plantarum (LP) on the physiological performance and intestinal microecology of juvenile Japanese [...] Read more.
Prophylactic antibiotic use in intensive aquaculture promotes antimicrobial resistance, necessitating the development of microbial-based interventions. This study evaluated the individual, complementary, and synergistic effects of Bacillus subtilis natto (BSN) and Lactobacillus plantarum (LP) on the physiological performance and intestinal microecology of juvenile Japanese flounder (Paralichthys olivaceus). Over a 60-day trial, juveniles (initial weight: 5.81 ± 0.03 g) received a basal diet (CON) or a diet supplemented with 107 CFU/g of BSN, LP, or both (BSN+LP). The BSN+LP consortium elicited complementary improvements in final body weight (21.39 ± 0.75 g vs. 18.66 ± 0.44 g in CON) and feed conversion efficiency (p < 0.05). Transcriptomic analysis revealed synergistic upregulation of digestive proteases (trypsin, chymotrypsin). Notably, an in pro-inflammatory markers (IL-1β, TNF-α) was counterbalanced by substantial upregulation of anti-inflammatory cytokines (IL-10, 5.65-fold; TGF-β1, 4.48-fold), suggesting the induction of mucosal tolerance rather than pathological enteritis. High-throughput 16S rRNA sequencing showed that the control cohort had a potential baseline microbial, characterized by a high relative abundance of Proteobacteria. BSN+LP administration significantly altered this microbial community into a fermentative eubiosis enriched in Firmicutes and Bacteroidota. Correlation network analyses confirmed negative interaction dynamics: increased abundance of Lactobacillus, Bacteroides, and Muribaculaceae was negatively correlated with baseline pathobiont abundance. These findings indicate that co-administration of BSN and LP hypothetically enhances metabolic energy harvest via short-chain fatty acid-producing taxa, strengthens the gut–immune axis, and competitively mitigates opportunistic pathogens. Full article
17 pages, 7593 KB  
Article
Bone Regeneration Drug BMP-7 Mitigates Ponatinib-Induced Cardiotoxicity via Inhibition of Pyroptosis and Modulation of TGF-β/SMAD Signaling Pathway
by Jonatas M. Rolando and Dinender K. Singla
Cells 2026, 15(9), 762; https://doi.org/10.3390/cells15090762 (registering DOI) - 24 Apr 2026
Abstract
Background: Ponatinib (PON), an effective tyrosine kinase inhibitor for leukemias harboring the T315I mutation, is limited by severe cardiotoxicity, including myocardial infarction and heart failure. Here, we investigated the therapeutic potential of Bone Morphogenetic Protein-7 (BMP-7), an anti-inflammatory growth factor, in a murine [...] Read more.
Background: Ponatinib (PON), an effective tyrosine kinase inhibitor for leukemias harboring the T315I mutation, is limited by severe cardiotoxicity, including myocardial infarction and heart failure. Here, we investigated the therapeutic potential of Bone Morphogenetic Protein-7 (BMP-7), an anti-inflammatory growth factor, in a murine model of PON-induced cardiotoxicity. Methods: C57BL/6J mice were distributed into experimental groups receiving PON (25 mg/kg cumulative dose) either alone or with BMP-7 (600 μg/kg cumulative dose), along with a corresponding control group. Cardiac analyses included molecular and histological assessments. Results: PON administration induced a marked increase in monocyte infiltration and M1 macrophage polarization. These inflammatory events led to the upregulation of the pyroptotic cascade, leading to activation of the TGF-β1/SMAD2/3 signaling axis. In contrast, BMP-7 significantly attenuated these pathological responses by suppressing inflammation-induced pyroptosis and the TGF-β1/SMAD2/3 signaling axis. Conclusions: These findings identify inflammation-induced pyroptosis as a central driver of the pathological changes in PON-induced cardiotoxicity. Notably, our work highlights BMP-7’s capacity to inhibit these disease-related alterations. Collectively, these results expand on the current knowledge of the mechanistic framework of PON-induced cardiotoxicity, while also emphasizing BMP-7 as a promising therapeutic candidate with potential translational relevance. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Heart Regeneration)
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25 pages, 3567 KB  
Article
Human Milk Oligosaccharide LNnT Attenuates Colonic Barrier Dysfunction and Associated Cognitive Impairment via Modulating Sphingolipid Metabolism and Gut Microbiota
by Minghui Wang, Liuying Zhu, Jinqiang Liao, Lulu Bao, Hongyan Li, Zeyuan Deng, Jing Li, Liufeng Zheng and Bing Zhang
Molecules 2026, 31(9), 1410; https://doi.org/10.3390/molecules31091410 - 24 Apr 2026
Abstract
This study focuses on Lacto-N-neotetraose (LNnT), a core component of human milk oligosaccharides. Although LNnT has been demonstrated to promote early intestinal development and maintain gut homeostasis, its protective mechanism against D-galactose-induced intestinal injury and associated cognitive impairment remains unclear. This investigation systematically [...] Read more.
This study focuses on Lacto-N-neotetraose (LNnT), a core component of human milk oligosaccharides. Although LNnT has been demonstrated to promote early intestinal development and maintain gut homeostasis, its protective mechanism against D-galactose-induced intestinal injury and associated cognitive impairment remains unclear. This investigation systematically examined the protective effects and underlying mechanisms of LNnT against D-gal-induced colonic damage and cognitive impairment in mice. The results demonstrated that LNnT not only significantly improved systemic physiological phenotypes and upregulated the expression of colonic tight junction proteins to repair the intestinal barrier, but also effectively enhanced learning and memory abilities in mice. Concurrently, LNnT reduced serum proinflammatory factor levels, elevated the anti-inflammatory factor IL-10, and alleviated oxidative stress. Furthermore, LNnT remodeled the gut microbiome structure by increasing microbial diversity, enhancing beneficial bacteria abundance, and promoting short-chain fatty acid production. Untargeted metabolomics analysis further revealed that LNnT corrected metabolic disturbances by regulating key sphingolipid molecules (ceramide, sphingosine, S1P) and the expression of related metabolic enzymes (ACER2, SphK2). In summary, this study suggests that LNnT mitigates intestinal injury and improves cognitive function, potentially through modulation of the gut microbiota–sphingolipid metabolism axis, although further causal validation is warranted. These findings provide a mechanistic foundation for future studies exploring its potential as a functional dietary ingredient. Full article
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24 pages, 1923 KB  
Review
Mogrosides as Dual-Function Sweeteners: A Comprehensive Review of Extraction, Metabolism, Antidiabetic Mechanisms, and Food Applications
by Qiqi Feng, Tao Wang, Qing Wang, Hongyu Pan, Yujie Zhong and Yongliang Zhuang
Nutrients 2026, 18(9), 1342; https://doi.org/10.3390/nu18091342 - 24 Apr 2026
Abstract
Mogrosides, the primary bioactive compounds of Siraitia grosvenorii, are natural, non-caloric sweeteners with promising therapeutic potential for diabetes. They provide a dual advantage: delivering sweetness without impacting blood glucose levels, while simultaneously exerting beneficial antidiabetic effects. This review systematically synthesizes current knowledge [...] Read more.
Mogrosides, the primary bioactive compounds of Siraitia grosvenorii, are natural, non-caloric sweeteners with promising therapeutic potential for diabetes. They provide a dual advantage: delivering sweetness without impacting blood glucose levels, while simultaneously exerting beneficial antidiabetic effects. This review systematically synthesizes current knowledge on mogrosides, covering their extraction methods, metabolic pathways, and underlying antidiabetic mechanisms. We first detail key extraction techniques and examine their metabolic fate, which is primarily characterized by gut microbiota-mediated deglycosylation leading to the formation of mogrol. Subsequently, the antidiabetic efficacy of mogroside-rich extracts and pivotal monomeric derivatives is critically evaluated, with an emphasis on mechanistic insights such as AMP-activated protein kinase (AMPK) pathway activation, anti-inflammatory and antioxidant activities, immunomodulatory effects, and the regulation of gut microbiota. It is important to note that due to the limitation of clinical trial data, most of the evidence reviewed derives from in vitro studies or animal models. Finally, their emerging role as functional ingredients within the food industry was discussed. Collectively, this review aimed to establish a robust scientific foundation for the development of mogrosides as safe, plant-derived sweeteners endowed with enhanced health-promoting properties for the prevention and management of diabetes. Full article
(This article belongs to the Section Nutrition and Diabetes)
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33 pages, 1626 KB  
Article
Fractional Reaction–Diffusion Modelling of Immune-Mediated Demyelination in Multiple Sclerosis Under IFN-Beta and Glatiramer Acetate Therapy
by Aytekin Enver, Fatma Ayaz, Mehmet Yavuz and Fuat Usta
Fractal Fract. 2026, 10(5), 281; https://doi.org/10.3390/fractalfract10050281 - 23 Apr 2026
Abstract
We propose a dimensionally consistent fractional spatio-temporal PDE framework for modelling immune-mediated demyelination in multiple sclerosis (MS). The system couples effector and regulatory T cells, M1/M2 macrophage polarisation, pro- and anti-inflammatory cytokines, oligodendrocyte dynamics, and time-dependent therapeutic controls within a unified distributed-parameter structure. [...] Read more.
We propose a dimensionally consistent fractional spatio-temporal PDE framework for modelling immune-mediated demyelination in multiple sclerosis (MS). The system couples effector and regulatory T cells, M1/M2 macrophage polarisation, pro- and anti-inflammatory cytokines, oligodendrocyte dynamics, and time-dependent therapeutic controls within a unified distributed-parameter structure. In contrast to ad hoc replacements of integerorder derivatives by Caputo fractional derivatives, the fractional extension proposed here is derived from an underlying continuous-time random walk (CTRW) process with Mittag–Leffler-distributed residence times. This stochastic derivation yields a governing system in which a single commensurate fractional order α ∈ (0, 1], together with a characteristic memory timescale τ0, ensures dimensional consistency and mass balance across all coupled components. The model is formulated as a system of nonlinear reaction–diffusion equations with cross-regulatory and multiplicative interaction terms governing immune amplification, cytokine feedback, and the demyelination–remyelination balance. Analytical interpretation shows how non-Markovian residence times induce Mittag–Leffler-type relaxation and thereby modify effective growth, decay, and stability properties. Numerical simulations compare classical and fractional dynamics, revealing that memory-driven kinetics prolong effector T-cell and M1-macrophage activity, attenuate reparative M2 and oligodendrocyte responses, and extend the effective action of bang–bang therapy inputs representing IFN-β and glatiramer acetate beyond their dosing windows. The results indicate that integer-order models may underestimate chronic inflammatory persistence and demyelination severity, while providing a mathematically and physically well-posed platform for memory-aware immune modelling and therapy evaluation in MS. Full article
27 pages, 760 KB  
Review
Bioactive Compounds in Coffee: Metabolism, Bioavailability and Health Effects—A Review
by Hajnal Finta, Sándor Pál, Margit Solymár, Zsuzsanna Faust, Marius-Călin Cherecheș, Florina Ruța, Daniela-Edith Ceană, Corneliu-Florin Buicu and Enikő Nemes-Nagy
Molecules 2026, 31(9), 1404; https://doi.org/10.3390/molecules31091404 - 23 Apr 2026
Abstract
Coffee is a very popular psychoactive beverage with a complex composition. Besides its stimulant effect due to caffeine, it contains several bioactive compounds with antioxidant properties and potent metabolic activity. Its clinical efficacy is fundamentally determined by the bioavailability and metabolic fate of [...] Read more.
Coffee is a very popular psychoactive beverage with a complex composition. Besides its stimulant effect due to caffeine, it contains several bioactive compounds with antioxidant properties and potent metabolic activity. Its clinical efficacy is fundamentally determined by the bioavailability and metabolic fate of its constituents. The bioactive components of coffee, such as polyphenols, melanoidins, phytosterols, biogenic amines, and carotenoids, have notable antioxidant, anti-inflammatory, and immunomodulatory effects. This review aims to present the main bioactive components of coffee, their biological effects, mechanisms of action, and the influence of preparation methods and individual variability on metabolic outcomes in common chronic diseases. The data are synthesized from clinical, prospective, and interventional studies to examine how processing variables and biological metabolism influence the health-promoting potential of coffee antioxidants. Brewing methods like hot filtration optimize the extraction of these antioxidants. Individual clinical outcomes are further modulated by genetic polymorphisms and gut microbiota variability, which influence the activation of the cellular Nrf2 antioxidant defense pathway. Full article
(This article belongs to the Special Issue Bioavailability of Bioactive Food Compounds)
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