Search Results (3,906)

With changes in lifestyle and dietary patterns, the incidence of prostate cancer in China has been increasing steadily, and it has become one of the most common malignancies in men. Chemotherapy remains a primary treatment for prostate cancer, but the subsequent development of drug resistance by tumor cells markedly compromises its therapeutic efficacy. Growth differentiation factor 15 (GDF15) has been shown to be closely associated with tumor cell proliferation and metastasis; however, its contribution to the drug resistance of prostate cancer cells within the tumor microenvironment has not been systematically investigated. In this study, we treated drug-resistant prostate cancer cells (PC3-TXR and DU145-TXR) with conditioned medium (CM) and examined GDF15 expression by Western blotting, real-time PCR, and ELISA. We then exposed drug-resistant cells to various concentrations of recombinant GDF15 (rGDF15) and CM, and assessed invasive and metastatic abilities as well as sensitivity to paclitaxel using Transwell and CCK-8 assays. We generated GDF15-knockout osteocytes using CRISPR-Cas9 technology and detected the expression of resistance-related signaling pathway components and epithelial–mesenchymal transition (EMT) markers. These findings were further validated through subcutaneous tumor formation assays in mice combined with immunohistochemistry to explore the mechanism by which GDF15 regulates drug resistance and metastasis in the crosstalk between drug-resistant prostate cancer cells and bone cells. Our results revealed that GDF15 expression was significantly upregulated in both drug-resistant prostate cancer cells and their surrounding microenvironment. rGDF15 enhanced the invasion and drug resistance of resistant cells, whereas knockout of GDF15 effectively inhibited these effects. Furthermore, we demonstrated that GDF15 regulates the biological behavior of drug-resistant cells by targeting and modulating the AKT signaling pathway and by promoting EMT initiation and progression. These findings clarify the molecular pathway through which GDF15 governs drug resistance in prostate cancer cells, offering a new direction for the treatment of tumor metastasis and biologically targeted therapy. Full article

Background: Maxillary hypoplasia and skeletal Class III malocclusion are deeply intertwined with upper airway constriction and paranasal sinus dysfunction. Conventional orthopedic interventions often struggle to achieve true 3D skeletal translation without inducing undesirable rotational side effects. The Right Angle Maxillary Protraction Appliance (RAMPA) therapy offers a biomimetic and mechanotherapeutic approach, focusing on anterosuperior protraction to restore both structural harmony and respiratory function. Methods: Structured as a comprehensive narrative review, this feature paper thoroughly reviews the multi-disciplinary evidence supporting RAMPA therapy by synthesizing our group’s recent computational (FEM, CFD) and clinical findings alongside the broader literature. We examine Finite Element Method (FEM) simulations detailing sutural mechanotransduction and osteogenic “BMP-2 Trigger Zones”, Computational Fluid Dynamics (CFD) utilizing shear-thinning rheological models for two-phase air–mucus interactions, and large-cohort CBCT and Coben analyses quantifying longitudinal growth. Results: FEM studies confirm that RAMPA, especially when combined with intraoral devices (e.g., gHu-1, VomPress, Hybrid), achieves predictable anterosuperior displacement and concentrates tensile stress to levels hypothesized to stimulate molecular bone remodeling. CFD simulations reveal that this precise skeletal remodeling optimizes wall shear stress (WSS) and theoretically facilitates paranasal mucus clearance via enhanced suction and shear-thinning effects. Clinically, RAMPA induces a 1.2-fold acceleration in natural sinonasal growth velocity. Furthermore, volumetric gains are distinctively pronounced in patients with pre-existing empyema (61.2% increase) compared to those with clear sinuses (18% increase), indicating rapid pathophysiological obstruction relief. Conclusions: By integrating controlled biomechanical forces with fluid-dynamic airway optimization, RAMPA therapy acts as a mechanotherapeutic modulator. It bridges the gap between mechanical intervention, molecular signaling, and physiological homeostasis, offering a comprehensive paradigm for pediatric craniofacial and respiratory restoration. Full article

Vascularization remains a fundamental bottleneck in tissue engineering, as the absence of functional vascular networks limits oxygen and nutrient delivery, resulting in necrotic cores and poor host integration. While structural scaffold design and cell sourcing have advanced considerably, emerging evidence indicates that paracrine signaling, rather than direct cell contact or scaffold architecture alone, is the primary driver of angiogenesis and vasculogenesis within engineered constructs. Key cell types, including endothelial cells (ECs) and mesenchymal stem cells (MSCs), engage in bidirectional paracrine crosstalk through the secretion of vascular endothelial growth factor (VEGF), angiopoietins, hepatocyte growth factor, and platelet-derived growth factor, among other mediators. While researchers have long focused on improving scaffold structure and cell selection, growing evidence shows that the chemical messages cells send to one another play a far more important role in driving blood vessel formation than previously appreciated. This review explores how cells embedded within engineered scaffolds communicate through secreted signals to coordinate the growth of new blood vessels. Two cell types, MSCs and ECs, are central to this process: cells that line blood vessels and bone marrow-derived stem cells. These cells exchange a variety of chemical messages that instruct neighboring cells to multiply, move, and organize into vessel-like structures. Importantly, the material properties of the scaffold itself, including its stiffness, surface texture, and degradation over time, influence the signals cells produce and how those signals spread through the tissue. Strategies to amplify paracrine signaling include growth factor-loaded delivery systems, hypoxic and genetic preconditioning of MSCs, and perfusion bioreactor culture. In vitro and in vivo evidence consistently demonstrates that coculture systems leveraging paracrine interactions produce superior vascular outcomes compared to single-cell or acellular constructs. Despite this progress, challenges related to signaling complexity, reproducibility, and clinical translation persist. Integration of transcriptomic and proteomic profiling, computational modeling, and machine learning approaches offers a path toward rationally designed scaffolds that recapitulate the spatiotemporal dynamics of native vascular signaling and ultimately support functional tissue regeneration. Full article

The development of reusable and biocompatible biomaterial-based culture substrates is increasingly relevant for improving sustainability in biomedical research workflows. In this study, polyethylene terephthalate glycol-modified (PETG) was evaluated as a potential alternative to conventional polystyrene (PS) for in vitro cell culture applications. PETG substrates were fabricated through laser cutting and tested for their ability to support cell adhesion, viability, proliferation, and lineage-specific differentiation across multiple human cell models, including calvarial mesenchymal stromal cells (CMSCs), bone marrow-derived mesenchymal stromal cells (hBM-MSCs), dermal fibroblasts, LHCN-M2 myoblasts, and SH-SY5Y neuroblastoma cells. Morphological and immunofluorescence analyses demonstrated that PETG supported cell attachment and focal adhesion formation, comparable to standard PS surfaces. Cell viability and proliferation assays confirmed metabolic activity and growth over time. Furthermore, PETG substrates supported osteogenic, adipogenic, myogenic, and neuronal differentiation, as demonstrated by histological staining, myotube formation, neurite outgrowth, and lineage-specific gene expression analyses. Finally, PETG maintained CMSC morphology and metabolic activity after repeated recovery, ethanol/UV treatment, and gelatin re-coating, with comparable results between new substrates and those reused for up to three cycles. These findings support PETG as a biocompatible culture substrate with preliminary short-term reuse potential and possible sustainability benefits for laboratory workflows. Full article

Micro-fragmented adipose tissue (mFAT) is a promising autologous biologic in regenerative medicine because it provides a mechanically processed adipose-derived product that preserves native extracellular matrix architecture and a cellular milieu rich in mesenchymal stem cells, pericytes, growth factors, cytokines, and extracellular vesicles. Mechanistically, mFAT is hypothesized to act largely through paracrine signaling that dampens inflammation, supports vascular stabilization, and promotes cartilage and soft-tissue repair; in vitro data suggest modulation of osteoarthritic synovial macrophage signaling, including reductions in chemokines such as CCL2 and CCL3. Preparation involves liposuction harvest followed by closed, sterile mechanical processing without enzymatic digestion or cell expansion, aligning with “minimal manipulation” concepts relevant to regulatory frameworks. Preclinical animal studies generally demonstrate favorable effects on synovial inflammation and cartilage matrix markers (e.g., glycosaminoglycan content) with limited adverse events. Clinically, the strongest body of evidence is in knee osteoarthritis, where multiple prospective and retrospective studies report improvements in pain and function from months to several years after single injections, though response rates vary and study designs are heterogeneous. Evolving data support potential benefit in hip osteoarthritis and select tendon conditions, but cohorts remain small. Overall, mFAT appears safe and potentially effective, yet larger, standardized, long-term randomized controlled trials and comparative studies versus platelet-rich plasma and bone marrow aspirate concentrates are needed to clarify indications, dosing, durability, and mechanisms in vivo. Full article

Engineering multifunctional scaffolds that effectively promote bone regeneration while concurrently mitigating the risk of infection remains a significant challenge in the field of bone tissue engineering. In this study, we present the fabrication of electrospun poly(lactic acid) (PLA) nanofibrous composite scaffold (PLASrCu) incorporating strontium peroxide (SrO₂) and copper-doped hydroxyapatite (CuHA) particles. The resulting composite scaffold exhibited interconnected porous structures and extracellular matrix-like morphologies. Physicochemical characterization confirmed the preservation of PLA chemical structure and the successful incorporation of crystalline SrO₂ and CuHA phases, with the tensile strength increasing from 2.3 to 2.8 MPa. The PLASrCu scaffold exhibited sustained ion release of Sr and Cu (12.2 and 13.3 mg/L, respectively, over 14 days), together with controlled oxygen generation (10.2 mg/L within 30 min), particularly under hypoxic conditions. In vitro biological assessments demonstrated that the PLASrCu scaffold significantly enhanced cell proliferation and viability. Moreover, osteogenic differentiation and mineralization were markedly promoted, as evidenced by upregulated expression of COL1, OPN, and RUNX2 (5.1-, 2.6-, and 1.9-fold increases, respectively) and increased calcium deposition. Importantly, the Cu-containing scaffolds effectively inhibited the growth of Staphylococcus aureus and Pseudomonas aeruginosa, resulting in antibacterial rates above 99.9%. Collectively, these results demonstrate that the PLASrCu nanofibrous scaffold integrates osteogenic, oxygen-generating, and antibacterial functions within a single platform, highlighting its strong potential for the regeneration of infected and oxygen-deficient bone defects. Full article

Intranasal corticosteroids (INCS) remain the cornerstone of pharmacologic treatment for allergic rhinitis (AR) because of their well-established anti-inflammatory efficacy and generally favorable benefit–risk profile. Nevertheless, concerns regarding local and systemic corticosteroid-related adverse events (AEs) continue to influence patient adherence, prescribing practices, and long-term treatment acceptance. In routine clinical practice, safety perception and corticosteroid-related concerns frequently influence adherence and formulation selection to a greater extent than differences in clinical efficacy, particularly in pediatric populations and in patients requiring prolonged continuous therapy. Differences in pharmacokinetic and pharmacodynamic properties, including systemic bioavailability, glucocorticoid receptor affinity, lipophilicity, protein binding, and extent of first-pass metabolism, are considered important safety profile determinants of currently available INCS formulations. Available evidence indicates that local AEs, particularly epistaxis, nasal irritation, dryness, and sensory discomfort, represent the most frequently reported treatment-related AEs across INCS formulations, although these events are generally mild, self-limiting, and infrequently treatment-limiting. Clinically significant structural nasal complications, including septal perforation or progressive mucosal injury, appear uncommon in currently available studies. Systemic AEs, including hypothalamic–pituitary–adrenal (HPA) axis suppression, ocular toxicity, growth impairment, or clinically meaningful effects on bone metabolism, have not been consistently demonstrated with currently used low-systemic-exposure formulations administered at recommended therapeutic doses. Although systemic glucocorticoid exposure has been associated with alterations in lipid metabolism, adipose tissue function, and metabolic homeostasis, currently available intranasal corticosteroids demonstrate minimal systemic exposure, making clinically relevant metabolic effects unlikely under recommended therapeutic conditions. Formulations such as mometasone furoate, fluticasone propionate, fluticasone furoate, and ciclesonide exhibit pharmacokinetic characteristics associated with minimal systemic exposure because of extensive first-pass metabolism and low oral bioavailability. Although substantial pharmacokinetic differences exist between currently available INCS formulations, direct comparative evidence demonstrating clinically meaningful superiority in systemic safety outcomes remains limited. Current evidence suggests that formulation-dependent differences are clinically more relevant with respect to local tolerability, sensory characteristics, patient preference, and long-term adherence than major systemic safety outcomes. Pediatric evidence is generally reassuring, although historical concerns regarding growth suppression associated with earlier corticosteroid formulations continue to influence clinical practice. Currently available evidence supports the use of modern INCS as effective and generally well-tolerated therapeutic options across adult and pediatric populations. Full article

Guided Bone Regeneration (GBR) is a pivotal technique in dental and orthopedic applications for regenerating bone in areas of deficiency. Natural polymers such as collagen, chitosan, alginate, and gelatin have emerged as essential materials in GBR due to their biocompatibility, biodegradability, and bioactivity. These polymers not only provide a scaffold for bone regeneration but also support cellular adhesion, proliferation, and differentiation. Despite their benefits, challenges such as variable degradation rates, insufficient mechanical strength, and limited bioactivity hinder their optimal clinical use. To address these limitations, ongoing research focuses on enhancing the properties of natural polymers. Composite materials combining fast- and slow-degrading polymers are being developed to achieve consistent degradation rates. Surface modifications, including nanoscale texturing and growth factor coatings, are improving bioactivity. Nanotechnology further enhances the structural and therapeutic potential of GBR materials, while advancements in 3D bioprinting enable the creation of customized scaffolds with precise architecture. These innovations aim to bridge the gap between biological compatibility and clinical functionality, making natural polymers more adaptable and effective in GBR. This review highlights the mechanisms, challenges, and advancements in natural polymers for GBR, emphasizing their potential to transform bone regeneration into a more reliable and patient-centered approach. Full article

The objective of this study was to evaluate the effects of fermented rapeseed meal (FRSM) replacing soybean meal (SBM) on growth performance, carcass traits, meat quality, serum biochemical parameters, and intestinal morphology in finishing pigs. Fifty healthy barrows (Duroc × Landrace × Yorkshire, DLY) were randomly assigned to five groups (n = 10): group A (control, soybean meal-based diet with 0% FRSM) and groups B, C, D, and E with 2.8%, 5.6%, 8.4%, and 11.2% FRSM inclusion, respectively. FRSM inclusion had no significant effect on growth performance. Compared with group A, group C showed greater bone weight and backfat thickness (p < 0.05), whereas group D had a lower dressing percentage (p < 0.05). Meanwhile, group D showed improved pressing loss and increased levels of arachidonic acid and α-linolenic acid (p < 0.05). Serum analysis revealed reduced malondialdehyde and elevated alanine, methionine, lysine, and cysteine concentrations in group D (p < 0.05). Jejunal villus height and villus height-to-crypt depth ratio were significantly increased in groups D and E, indicating improved intestinal morphology. However, group E reduced colonic acetic acid concentration. Adding 8.4% FRSM improved fatty acid composition, meat quality, and intestinal structure without compromising growth performance, suggesting that FRSM is a viable and sustainable alternative protein source in finishing pig diets. Full article

The aim of the study was to compare the production results, slaughter value, and physicochemical and biochemical parameters of the muscles of Ross 308 broiler chickens. The study included 225 individuals divided into three groups of 75 birds each. Each group was subdivided into three subgroups of 25 birds each (replicates). The control group received zinc (Zn) in the form of zinc oxide (ZnO) and copper (Cu) in the form of copper (II) sulfate pentahydrate (CuSO₄·5H₂O). Experimental group I received the microelements zinc and copper exclusively in the form of zinc hydroxychloride and dicopper chloride trihydroxide. Experimental group II received zinc and copper in both inorganic and hydroxychloride forms. The obtained results were processed using statistical analysis using the STATISTICA 13.0 [2016] program. The significance of differences between groups was inferred based on Tukey’s test. Chickens from the experimental groups were characterized by higher body weight (p ≤ 0.05) and eviscerated carcass weight (p ≤ 0.05) and better feed utilization (p ≤ 0.05). Moreover, compared with the control group, the carcasses of chickens from the experimental groups were characterized by a lower weight of breast muscles (p ≤ 0.05) and skin with subcutaneous fat, a similar weight of leg muscles, and a significantly greater weight of the remaining carcass components (p ≤ 0.01). The use of Zn and Cu in the form of hydroxychlorides in broiler chicken nutrition increased the fat content in the muscles (p ≤ 0.05), the concentrations of Zn and Cu in the liver, and significantly improved the tibial bone strength of broiler chickens. The application of Zn and Cu in the form of hydroxychlorides in the diets (experimental groups I and II) enhanced lipid and protein oxidation processes and the overall antioxidant capacity in the breast muscle. To conclude, dietary supplementation with zinc and copper hydroxychlorides in broilers promotes growth performance, bone strength, and mineral bioavailability, though it reduces breast muscle yield and triggers oxidative stress in these tissues. Full article

Layer chickens have dual physiological demands for rapid growth and continuous egg production. The maintenance of skeletal homeostasis in layer chickens relies on the precise coordination among OCs, osteoblasts (OBs), and osteocytes. The imbalances in the supply of nutrients such as calcium (Ca) and phosphorus (P), as well as dysfunction of the “gut–bone” axis, can disrupt normal bone development in layer chickens, leading to bone diseases such as tibial dyschondroplasia (TD) and osteoporosis (OP), seriously damaging the production performance of layer chickens. This review systematically summarizes the knowledge background of the metabolic reprogramming of OCs in layer chickens, especially mitochondria-mediated biological processes, including oxidative phosphorylation (OXPHOS), glycolysis, reactive oxygen species (ROS) signaling, mitophagy, etc. Notably, the co-culture system of OCs derived from the bone marrow cavity of embryos in vitro has been established in laying chickens. However, there are few reports on the study of mitochondrial metabolism of OCs using this model. Therefore, this review particular focuses on the bone metabolism mediated by OCs in layer chickens and proposes future research priorities, including the application of gene editing and multi-omics methods to ultimately achieve targeted nutritional or pharmacological interventions for optimizing mitochondrial function and promoting bone health. Full article

Follistatin (FST) binds to and neutralizes members of the transforming growth factor-beta (TGF-β) superfamily, thereby regulating diverse physiological processes, including regulation of skeletal muscle, adipose, and bone homeostasis. FST also promotes adipose browning and enhances energy metabolism, leading to improved plasma lipid profiles and metabolic health in mice. Given the emerging association between brown adipose tissue (BAT) activation and reduced atherosclerosis, we investigated the anti-atherogenic potential of FST. Transcriptomic and metabolomic analyses of the Hybrid Mouse Diversity Panel (HMDP) revealed that Fst expression was negatively correlated with aortic lesion area and positively correlated with the expression of multiple adipose browning-associated genes. Adeno-associated viral delivery of Fst (AAV1-FST344) in Ldlr^−/− mice significantly reduced aortic lesion area, improved plasma lipid profiles, and decreased expression of adhesion (VCAM1) and inflammatory (iNOS, TNF-α) markers in white adipose tissue (WAT), liver, and heart. Fst gene delivery also markedly increased uncoupling protein 1 (UCP1) expression in WAT, consistent with WAT browning. Integrated correlation analyses of Fst expression with tissue metabolites, together with plasma metabolite–lesion associations identified in the HMDP, implicated the arginase 1 (Arg1)-mediated metabolic pathway as a key regulator of atherogenesis. Consistent with these findings, Arg1 expression was significantly elevated in WAT, liver, and heart of AAV1-FST344-treated mice and in wild-type versus Fst-knockout mouse embryonic fibroblasts (MEFs). Immunostaining localized Arg1 predominantly to CD68⁺ macrophages in heart and liver. Given recent evidence identifying Arg1 as a novel mediator of efferocytosis, these findings suggest that Arg1 may promote macrophage metabolic reprogramming and resolution of inflammation by enhancing the clearance of apoptotic cells. Furthermore, Fst gene delivery increased the expression of fibroblast growth factor 21 (Fgf21) and adiponectin (AdipoQ) in WAT. Collectively, these findings identify Fst as a novel anti-atherogenic regulator that protects against vascular disease by promoting adipose browning, improving lipid metabolism, and activating Arg1-mediated metabolic pathways. Full article

Objective: This systematic review aimed to evaluate the effects of biomimetic surface engineering strategies applied to dental implants on osseointegration and peri-implant bone regeneration compared with conventional implant surfaces. Materials and Methods: A comprehensive literature search was conducted in the Web of Science, PubMed, and Scopus databases in accordance with the PRISMA guidelines, covering the period from January 2021 to January 2026. A total of 12 studies, including in vivo animal experiments and in vitro investigations, that met the inclusion criteria were analyzed. Risk of bias assessment was performed using the SYR-CLE tool and the ARRIVE guidelines. Results: Biomimetic strategies, including laser texturing, sulfonation, bioactive coatings, and growth factor/peptide functionalization (e.g., BMP-2, FGF-2, and PRF), significantly increased bone–implant contact (BIC), new bone volume (BV/TV), and biomechanical stability (pullout strength and reverse torque) compared to conventional surfaces. These surfaces enhance fixation under conditions of low bone density, such as osteoporosis, and improve infection resistance through antibacterial activity. In addition, these modifications enhance cellular adhesion, osteogenic differentiation, angiogenesis, and immune modulation. Conclusions: Current experimental evidence suggests that biomimetic implant surface engineering transforms dental implants from passive biomaterials into multifunctional bioactive interfaces capable of simultaneously regulating osteogenesis, immune response, angiogenesis, and antibacterial activity. Although promising outcomes have been demonstrated in preclinical studies, standardized long-term human clinical studies are still required to validate translational potential and long-term clinical efficacy. Full article

Periodontitis is a chronic inflammatory disease driven largely by dysregulated host responses that lead to destruction of periodontal tissues. Integrins are heterodimeric transmembrane receptors that regulate cell adhesion and bidirectional signaling in epithelial cells, immune cells, periodontal ligament fibroblasts, and osteoclasts. During disease progression, integrin-related responses may shift across overlapping molecular phases. Epithelial integrins such as α3β1 and α6β4 support barrier integrity, whereas α5β1 may facilitate microbial interaction and inflammatory signaling. β2 integrins and α4β1 contribute to leukocyte recruitment and inflammatory amplification, whereas increased α9β1-associated signaling and reduced αvβ6-mediated regulation of transforming growth factor β (TGF-β) may promote inflammatory persistence. Matrix-associated integrins, including α2β1 and α11β1, support extracellular matrix (ECM) organization and mechanotransduction, whereas αvβ3 cooperates with Receptor activator of nuclear factor kappa B ligand (RANKL) to promote osteoclast activity and alveolar bone resorption. Impaired β1 integrin-dependent signaling and potentially reduced αvβ5-associated efferocytosis may contribute to defective resolution and regeneration. Importantly, integrin expression, activation, and downstream signaling are distinct, and the strength of evidence varies among integrin subtypes. This review proposes a conceptual framework in which periodontitis reflects a dynamic imbalance in integrin-mediated processes that link inflammation, bone resorption, and regenerative failure, rather than being a direct equivalent of clinical periodontal stages or grades. Full article

As a traditional element of Chinese medicine, Hippocampus erectus is well known for promoting adolescent growth, yet its active fractions and underlying molecular mechanisms remain unclear. In this study, the aqueous extract of H. erectus was subjected to in vitro simulated gastrointestinal digestion and ultrafiltration to separate three molecular weight fractions (<10 kDa, 10–30 kDa, >30 kDa). Their chemical profiles were characterized, and osteogenic activities were systematically evaluated using cell assays, a juvenile rat model, and integrated transcriptomics and data-independent acquisition (DIA) proteomics. Results revealed that chemical profiling showed the >30 kDa fraction was mainly composed of hemocyanin subunits, and the 10–30 kDa fraction was enriched in growth-related amino acids and steroid derivatives; functionally, the 10–30 kDa fraction promoted preosteoblast proliferation and early differentiation via enhanced alkaline phosphatase (ALP) activity, while the >30 kDa fraction dominated late osteoblast maturation and mineralization. Both fractions significantly increased rat body and bone length by expanding growth plate proliferative zones and elevating serum insulin-like growth factor-1 (IGF-1)/bone morphogenetic protein-2 (BMP-2) levels. Transcriptomic and proteomic analyses identified vascular endothelial growth factor (VEGF), Wingless-related integration site (Wnt), phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt), and extracellular matrix (ECM)–receptor interaction as potential core regulatory pathways. Integrated multi-omics analysis further confirmed Frizzled-related protein B (Frzb) and AKT1 substrate 1 (Akt1s1) as candidate key regulatory targets enriched in the Wnt and adenosine monophosphate-activated protein kinase (AMPK) signaling pathways. These findings elucidate the multi-fraction, multi-pathway mechanism of H. erectus in promoting skeletal development, providing scientific evidence for its traditional use and a theoretical basis for growth-promoting functional food development. Full article