Search Results (868)

Plant-derived polynucleotides (PNs) have emerged as promising regenerative biomolecules; however, their mechanisms remain less defined than those of salmon-derived polydeoxyribonucleotides (S-PDRNs). Here, we extracted polynucleotides from Paeonia lactiflora callus (PL-PN) and evaluated their biological effects on human dermal fibroblasts. PL-PN treatment increased cell viability and pro-collagen I α1 secretion. PL-PN enhanced adenosine A2A receptor expression and activated the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP response element-binding protein (CREB) pathway, accompanied by increased Cyclin D1 levels, retinoblastoma protein (Rb) phosphorylation, and nuclear proliferating cell nuclear antigen (PCNA) levels, indicating an accelerated G1/S transition. PL-PN also significantly reduced nuclear NF-κB localization and downregulated MMP1, MMP3, MMP9, and MMP13, suggesting attenuation of inflammatory and catabolic signaling. Furthermore, PL-PN increased TGF-β maturation, Smad2/3 phosphorylation, and the transcription of COL1A1, COL3A1, and elastin, resulting in enhanced collagen and elastin deposition. These effects are comparable to those of S-PDRN. Although the pathway specificity and in vivo relevance require further studies, our findings provide evidence that PL-PN promotes extracellular matrix regeneration via coordinated proliferative, anabolic, and anti-inflammatory actions. Thus, PL-PN represents a potential sustainable plant-based alternative to S-PDRN for dermatological regeneration. Full article

Background: Myocardial fibrosis, a central pathological process leading to heart failure, lacks specific mechanism-based therapies. Although the anti-inflammatory activity of the natural compound protocatechuic acid is recognized, its direct anti-fibrotic mechanism, particularly concerning the critical role of endothelial–mesenchymal transition (EndMT), remains unexplored. This study aimed to investigate the protective effects and underlying mechanisms of protocatechuic acid. Methods: The study employed both in vivo and in vitro models. For in vivo evaluation, a rat model of myocardial fibrosis was induced by isoproterenol hydrochloride (ISO). For in vitro analysis, human umbilical vein endothelial cells (HUVECs) were stimulated with angiotensin II (Ang II) and subjected to siRNA-mediated histone deacetylase 1 (HDAC1) knockdown, alongside a co-culture model involving HUVECs and the AC16 human cardiomyocyte cells. Additionally, molecular docking and dynamics simulations were performed to evaluate the binding affinity and stability of protocatechuic acid with the target protein, HDAC1. Results: In vivo, protocatechuic acid significantly improved cardiac function, attenuated pathological injury, and reduced collagen deposition in ISO-induced fibrotic rats. It also potently suppressed inflammatory responses and inhibited the EndMT process. These beneficial effects were associated with decreased HDAC1 and increased GATA binding protein 4 (GATA4) expression in perivascular regions, which suggests the modulation of the HDAC1/GATA4 pathway. In vitro, protocatechuic acid suppressed Ang II-induced endothelial inflammation in HUVECs. This effect was replicated by HDAC1 knockdown, thus confirming that the HDAC1/GATA4 pathway mediates its anti-inflammatory action at the cellular level. Furthermore, molecular docking and dynamics simulations indicated that protocatechuic acid stably binds to a key target, HDAC1. Conclusions: Protocatechuic acid alleviates inflammation and EndMT by inhibiting the HDAC1/GATA4 signaling pathway, thereby preserving cardiac function and retarding the progression of myocardial fibrosis. These findings provide a theoretical and experimental foundation for the potential application of protocatechuic acid in treating cardiovascular diseases. Full article

Background: Pulmonary fibrosis (PF) currently lacks effective therapeutic interventions. Roxadustat, an oral small-molecule inhibitor of hypoxia-inducible factor prolyl hydroxylase, has been shown in several studies to attenuate the progression of fibrotic diseases. However, its therapeutic efficacy in PF remains to be fully elucidated. The aim of this study was to evaluate roxadustat’s therapeutic benefits on PF as well as the underlying mechanisms of action. Methods: Bleomycin was administered intraperitoneally to establish a PF mouse model. H&E staining, Masson staining, and immunohistochemistry (IHC) were used to assess histopathological and fibrotic changes. Changes in the expression levels of inflammatory mediators, including IL-1β, TGF-β1, and TNF-α, were examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Network pharmacology combined with transcriptomic analysis was employed to identify potential target genes and associated signaling pathways. Subsequently, RT-qPCR and Western blot analyses were carried out to experimentally validate the predicted targets and pathways and to verify the protective effects of roxadustat in PF mice. Results: Roxadustat markedly ameliorated bleomycin-induced pulmonary fibrosis in mice. The therapeutic effect was evidenced by a reduction in alveolar damage, thinner alveolar septa, diminished infiltration of inflammatory cells, and decreased collagen deposition. Concomitantly, the expression levels of inflammatory mediators, including IL-1β, TGF-β1, and TNF-α, were significantly lowered. Integrated network pharmacology and transcriptomic analyses revealed the involvement of critical signaling pathways, specifically nuclear factor-kappa B (NF-κB) and peroxisome proliferator-activated receptor (PPAR). Experimental validation further demonstrated that roxadustat downregulated the expression of key genes (S100A8, S100A9, and Fos) in murine lung tissues. It also suppressed the protein ratios of phosphorylated p65 to total p65 and phosphorylated IκBα to total IκBα. Moreover, roxadustat treatment upregulated PPARγ protein expression. Conclusions: These data indicate that roxadustat ameliorates bleomycin-induced PF in mice, an effect associated with modulation of the NF-κB and PPAR signaling pathways. The findings provide a preclinical rationale for further investigation of roxadustat as a potential treatment for PF. Full article

Background/Objectives: Hippocampal neuroinflammation (HNF) is a key pathological feature in neurodegenerative disorders. Milk-derived exosomes, as bioactive extracellular vesicles, have underexplored potential in regulating brain neuroinflammatory responses. This study aimed to characterize desert milk exosomes (D-Exo) and investigate their neuroprotective and anti-neuroinflammatory effects in LPS-induced HNF mice model and an LPS-stimulated BV2 microglia. Methods: Exosomes were isolated from desert and non-desert milk (ND-Exo) for proteomic analysis. After pretreating BV2 cells with exosomes and stimulating with LPS, their inflammatory responses and polarization were assessed by RT-PCR. Balb/c mice were orally gavaged with D-Exo or 0.9% NaCl for 28 days before LPS injection. Cognitive function was assessed via behavioral tests, with microglial/astrocyte activation analyzed by immunofluorescence. Results: D-Exo exhibited superior stability and a unique proteomic profile enriched with proteins linked to neuroinflammation and blood-brain barrier (BBB) integrity, notably within the AMPK signaling pathway. In vitro, D-Exo shifted LPS-stimulated microglia from the M1 to the M2 phenotype. In vivo, it alleviated HNF and cognitive decline, reduced Aβ_1-42 and Tau deposition, elevated BDNF and MAP2, and suppressed neuroinflammation and glial activation. Conclusions: D-Exo is enriched with specific proteins, attenuates neuroinflammation and cognitive decline by regulating microglial M1/M2 polarization and AMPK pathway, highlighting its preventive potential. Full article

Background/objectives: Cannabidiol (CBD) is a non-psychoactive constituent of Cannabis sativa, which has potential skeletal benefits through modulation of bone cell function and inflammatory signalling. However, evidence of its effects and mechanisms in bone health remains fragmented. This scoping review summarised the current findings on the impact of CBD on bone outcomes and its mechanisms of action. Methods: A systematic search of PubMed, Scopus, and Web of Science was conducted in October 2025 for original studies published in English, with the primary objective of examining the effects of CBD on bone health, regardless of study design. After applying inclusion and exclusion criteria, 24 primary studies were included. Data on model design, CBD formulation, treatment parameters, bone-related outcomes, and proposed mechanisms were extracted and analysed descriptively. Results: Among the studies included, eleven demonstrated beneficial effects of CBD on bone formation, mineralisation, callus quality, or strength; eleven showed mixed outcomes; and two demonstrated no apparent benefit. Previous studies have shown that CBD suppresses bone resorption by reducing osteoclast differentiation and activity while promoting osteoblast proliferation and matrix deposition. Mechanistically, CBD’s effects involve activation of cannabinoid receptor 2, modulation of the receptor activator of nuclear factor-κB ligand/osteoprotegerin pathway, and regulation of osteoblastogenic and osteoclastogenic signalling through bone morphogenetic protein, Wnt, mitogen-activated protein kinase, nuclear factor-κB, and peroxisome proliferator-activated receptor signalling. The anti-inflammatory and antioxidant actions of CBD further contribute to a favourable bone microenvironment. Conclusions: Preclinical evidence suggests that CBD has a bone-protective role through multifaceted pathways that enhance osteoblast function and suppress osteoclast activity. Nevertheless, robust human trials are necessary to confirm its efficacy, determine its optimal dosing, and clarify its long-term safety. Full article

Lignocellulosic bio-based materials, such as wood, biocomposites, and natural fibers, exhibit desirable structural properties. This comprehensive review emphasizes the foundational and latest advancements in bioinspired improvement strategies, such as direct mineralization, biomineralization, lignocellulosic nanomaterials, protein-based treatments, and metal-chelating processes. Significant focus was placed on biomimetics, emulating natural protective mechanisms, with discussions on relevant topics including hierarchical mineral deposition, free-radical formation and quenching, and selective metal ion binding, and relating them to lignocellulosic bio-based material property improvements, particularly against fire and fungi. This review evaluates the effectiveness of different bioinspired processes: mineralized and biomineralized composites improve thermal stability, nanocellulose and lignin nanoparticles provide physical, thermal, and chemical barriers, proteins offer biochemical inhibition and mineral templating, and chelators interfere with fungal oxidative pathways while simultaneously improving fire retardancy through selective binding with metal ions. Synergistic approaches integrating various mechanisms could potentially lead to long-lasting and multifunctional protection. This review also highlights the research gaps, challenges, and potential for future applications. Full article

Simultaneously inhibiting beta-amyloid protein (Aβ) aggregation and reducing metal ion overload in the brain is a promising strategy for treating Alzheimer’s disease (AD). Aloe emodin (AE) is one of the major components of the traditional Chinese medicine rhubarb. Based on its reported pharmacological effects and its structural affinity for metal ions, this study aims to explore the potential of AE in improving AD pathology. Through the injection of Aβ or copper-Aβ complex in the bilateral hippocampus of rats, we constructed two kinds of nontransgenic animal models. Behavioral tests were used to evaluate cognitive impairment, and the effects of AE on neuronal damage and Aβ deposition were measured via Nissl staining and immunohistochemistry. Furthermore, we detected copper content in the serum and brain tissues as well as some biochemical indexes of Aβ cascade pathology in the brain tissues of model rats to explore the mechanism of action. AE treatment decreased copper accumulation and regulated Aβ metabolism in the brain of model rats, thereby improving Aβ deposition, memory impairment, hippocampal nerve cell damage, and related biochemical indicators. AE ameliorated the AD pathology of the model rats by targeting copper-induced Aβ toxicity, revealing a mechanism of action by which AE may exhibit good clinical efficacy in treating AD. Full article

Amyloidosis is a group of disorders caused by extracellular deposition of insoluble fibrillar proteins, leading to progressive organ dysfunction. Cardiac amyloidosis is clinically significant, as myocardial infiltration results in restrictive cardiomyopathy, arrhythmias, and heart failure. The main subtypes are light-chain (AL) and transthyretin (ATTR) amyloidosis, while AA and isolated atrial amyloidosis (IAA) are less common. Accurate subtype identification is crucial for management and prognosis. Diagnosis requires a multimodal approach combining imaging and tissue-based techniques. Echocardiography is usually first-line, showing increased wall thickness, biatrial enlargement, and apical sparing. Cardiac magnetic resonance (CMR) provides superior tissue characterization through late gadolinium enhancement and elevated extracellular volume. Nuclear scintigraphy with 99mTc-labeled tracers enables non-invasive ATTR detection, while amyloid-specific PET tracers show potential for early diagnosis. Histochemical confirmation remains essential. Congo Red staining with apple-green birefringence under polarized light is the diagnostic gold standard, supported by Thioflavin T, PAS, and Alcian Blue stains. Immunohistochemistry and mass spectrometry aid amyloid typing, while electron microscopy provides ultrastructural confirmation. Integrating imaging, histochemical, immunohistochemical, and proteomic techniques enhances early recognition and precise classification, improving therapeutic strategies and patient outcomes. Full article

Determining protein requirements (PRs) for dogs remains a longstanding challenge. During growth, the rapid rate of protein deposition increases the demand for amino acids. In adult dogs, differences in overall diet digestibility and lower energy requirements of domestic dogs have led to discrepancies between the minimum crude protein (CP) value proposed by the National Research Council (NRC; 80 g of CP/kg of diet) and the 180 g of CP/kg of diet proposed by the European Pet Food Industry Federation (FEDIAF) and the Association of American Feed Control Officials (AAFCO), although most commercially available adult dog feeds offer protein levels that exceed both recommendations. In elderly dogs, physiological changes such as sarcopenia and reduced energy intake indicate a potential increase in PR, although evidence remains scarce. A similar gap exists for pregnant and lactating bitches, since most recommendations rely on extrapolations from growth studies. Classical PR recommendations were based on body weight gain and nitrogen balance (NB), methods that present important limitations. Due to this, stable isotope methods—including ¹³C-leucine, ¹⁵N-glycine, and ¹³C-phenylalanine—have emerged as precise methodological tools, enabling a detailed and dynamic assessment of whole-body protein metabolism, protein quality, and more accurate determination of PR and recommended allowance across different life stages. Full article

Despite the recognized involvement of TTC39 family genes in metabolism related to pigment deposition, their evolutionary features and potential roles in body coloration in teleost fish remain largely unexplored. We identified three TTC39 genes in Plectropomus leopardus, conserved domains, and evolutionary relationships. The three genes (TTC39A, TTC39B, and TTC39C) were mapped to different chromosomes, yet they shared similar conserved protein domains. Phylogenetic and collinearity analyses indicated that TTC39 genes are evolutionarily conserved among Danio rerio. Gene structure and motif analyses further highlighted the homology and distributional diversity within the TTC39 family. Quantitative expression assays comparing red and black skin revealed significant upregulation of TTC39A and TTC39B in red skin, suggesting that these genes play a role in regulating skin color. These findings provide a foundation for future studies examining how TTC39 genes regulate red skin coloration in P. leopardus. Full article

The massive influx of pelagic Sargassum in the Caribbean poses a serious environmental, social, and economic problem, as the stranded biomass is often treated as waste and deposited in landfills. This literature review synthesizes recent research highlighting its potential for valorization in various industries, turning this challenge into an opportunity. Sargassum has low levels of protein and lipids. Still, it is particularly rich in carbohydrates, such as alginates, fucoidans, mannitol, and cellulose, as well as secondary metabolites, including phenolic compounds, flavonoids, pigments, and phytosterols with antioxidant and bioactive properties. These biochemical characteristics allow for its application in renewable energy (bioethanol, biogas, biodiesel, and combustion), agriculture (fertilizers and biostimulants), construction (composite materials, cement additives, and insulation), bioremediation (adsorption of heavy metals and dyes), and in the health sector (antioxidants, anti-inflammatories, and pharmacological uses). A major limitation is its high bioaccumulation capacity for heavy metals, particularly arsenic, which increases environmental and health risks and limits its direct use in food and feed. Therefore, innovative pretreatment and bioprocessing are essential to mitigate these risks. The most promising approach for its utilization is a biorefinery model, which allows for the sequential extraction of multiple high-value compounds and energy products to maximize benefits, reduce costs, and sustainably transform Sargassum from a coastal pest into a valuable industrial resource. Full article

Improving phosphorus (P) utilization in broilers is crucial for reducing feed costs and environmental pollution. Bone mineralization trait is strongly associated with P utilization in poultry and is thus often used as an alternative trait for evaluating P utilization. Dentin matrix protein 1 (DMP1), an essential matrix protein for bone mineralization and P deposition, has been shown to be actively involved in P utilization in broilers, but the underlying mechanisms remain unclear. The current study aimed to investigate the possible mechanisms whereby DMP1 regulates P utilization of poultry by using gene silencing and overexpression technologies, combined with an in vitro model of primary broiler osteoblasts. The results showed that DMP1 overexpression augmented the P utilization of broiler osteoblasts, characterized by significant increases (p < 0.001) in P utilization rate, mineralization formation, alkaline phosphatase activity, and bone gla protein content. Meanwhile, DMP1 overexpression effectively (p < 0.05) activated the focal adhesion kinase (FAK) signaling, along with obvious (p < 0.01) decreases in fibroblast growth factor 23 (FGF23) expression and production. In contrast, DMP1 silencing reversed (p < 0.05) the above effects. Consistently, FAK activation promoted (p < 0.05) P utilization accompanied by remarkable (p < 0.05) decreases in FGF23 expression and production. Furthermore, gain- and loss-of-function assays demonstrated that a high level of FGF23 contributed to impaired P utilization, while a low level was beneficial. Interestingly, blocking FAK signaling not only recovered (p < 0.05) the FGF23 expression and production in DMP1 overexpressed cells but also obviously (p < 0.05) weakened their P utilization. These findings indicate that DMP1 inhibits FGF23 expression by activating FAK, thereby contributing to P utilization in broiler osteoblasts. They reveal a novel DMP1-FAK-FGF23 regulatory axis in broiler osteoblasts and provide a potential target for improving P efficiency in poultry. Full article

Corilagin is a hydrolyzable ellagitannin and naturally occurring polyphenolic compound widely distributed in medicinal plants. It is also present in longan (Dimocarpus longan), known as lumyai in Thailand, a subtropical fruit extensively cultivated across China and Southeast Asia. Corilagin has been reported to exhibit strong antioxidant, anti-inflammatory, hepatoprotective, and anticancer activities through modulation of multiple cellular signaling pathways. However, despite these well-established pharmacological properties, its potential role in regulating bone marrow mesenchymal stem cell (BM-MSC) differentiation has not been fully explored in biomedical applications. In this study, we investigated the effects of corilagin on BM-MSC viability, protein-binding interactions, and lineage-specific differentiation toward osteogenic and chondrogenic pathways. Cytotoxicity assessment using human synovial SW-982 cells demonstrated that corilagin maintained cell viability at concentrations ranging from 1.56 to 50 µg/mL within 48 h, whereas prolonged exposure resulted in a time-dependent reduction in viability. In BM-MSCs, corilagin significantly enhanced osteogenic and chondrogenic differentiation in a dose-dependent manner, as evidenced by increased mineral deposition and cartilage matrix formation, as revealed by Alizarin Red S, Toluidine Blue, and Alcian Blue staining. Quantitative analyses further showed the upregulation of key lineage-specific genes, including Runx2 and osteopontin (OPN) for osteogenesis and Sox9 and aggrecan for chondrogenesis. Protein-binding assays confirmed the molecular interaction capacity of corilagin, supporting its biological activity. Overall, these findings demonstrate that corilagin promotes MSC-mediated osteogenic and chondrogenic differentiation while maintaining acceptable cytocompatibility, highlighting its potential as a natural small-molecule candidate for bone and cartilage tissue engineering and other biomedical fields with regenerative medicine applications. Full article

Human induced pluripotent stem cells (hiPSCs) offer significant potential for differentiation and research applications in cardiovascular diseases. When induced differentiated hiPSC-derived cardiomyocytes (hiPSC-CMs) are transplanted into the infarcted myocardial region, they exhibit extremely low survival rates and unsatisfactory therapeutic effects due to ischemia, hypoxia, and immune inflammation in the surrounding environment. To address this issue, we used Panax notoginseng saponin R1 (NGR1), which has demonstrated significant protective effects in prior research, to pretreat hiPSC-CMs before transplantation. Utilizing an in vitro H₂O₂ oxidative stress model and a nude mouse myocardial infarction (MI) model, we investigated the mechanism through which NGR1 pretreatment enhances the therapeutic efficacy of hiPSC-CM transplantation. The results revealed that the hiPSC-CMs expressed cTnT. NGR1 did not promote the proliferation of hiPSC-CMs but instead induced elevated levels of p-Akt protein in these cells. Compared to hiPSC-CM transplantation alone, transplantation of hiPSC-CMs pretreated with NGR1 exhibited higher ejection fraction (EF) and fractional shortening (FS) values, along with reduced infarct size and collagen deposition. Additionally, there were more HNA-positive cardiomyocytes in the cardiac tissue, fewer TUNEL-positive signals, and increased VWF-positive and Lyve1-positive signals. Furthermore, the gene expression levels of VEGFC, IGF-1, and SDF-1 were higher. Therefore, NGR1 pretreatment improves the survival of transplanted hiPSC-CMs in tissues, reduces myocardial apoptosis, enhances cardiac function, decreases infarct size and collagen deposition, promotes angiogenesis and lymphangiogenesis, and stimulates paracrine secretion. Full article

Lion-head goose is a large-sized breed native to Guangdong Province, China, exhibits remarkable capacity for fatty liver production under overfeeding conditions and is highly valued by local farmers and consumers. However, the molecular mechanisms driving fatty liver development in this breed are still unknown. In this study, we evaluated liver weight differences between normally fed and overfed Lion-head geese and further examined sex-specific differences following overfeeding. Overfeeding significantly increased liver weight more than 340%, and males possess a stronger capacity for lipid deposition under the same feeding regimen compared with females. RNA-Seq analysis identified 1476 differentially expressed genes (DEGs) shared by both sexes, which were mainly enriched in lipid and energy metabolism, oxidative stress, and mitochondrial pathways. In addition, 627 male-specific and 420 female-specific DEGs revealed sex-dependent differences, with males showing stronger transcriptional regulation and females exhibiting enhanced antioxidant and detoxification responses. Weighted gene co-expression network analysis (WGCNA) revealed 320 co-hub genes enriched in lipid and energy metabolism in overfeeding-induced fatty liver, along with 9 co-hub genes related to sex differences. Alternative splicing (AS) analysis detected 131 differentially spliced genes (DSGs). Integration of both approaches identified 7 overlapping genes, HYCC2 (Hyccin PI4KA lipid kinase complex subunit 2), AGL (Amylo-Alpha-1,6-Glucosidase and 4-Alpha-Glucanotransferase), CCDC62 (Coiled-coil domain containing 62), IGSF5 (Immunoglobulin superfamily member 5), MGARP (Mitochondria-localized glutamic acid-rich protein), CD80 (Cluster of Differentiation 80), and FPGS (Folylpolyglutamate synthase), as potential key regulators. These findings provide new insights into transcriptional and post-transcriptional regulation of overfeeding-induced fatty liver in geese. Full article