Search Results (3,137)

Survival rates in pediatric cancer have increased substantially over recent decades. However, children and survivors frequently experience treatment-related alterations in physical function, body composition, bone health, and metabolic regulation. Chemotherapy, glucocorticoid exposure, physical inactivity, nutritional imbalance, and inflammatory and neuroendocrine disturbances may contribute to reduced lean mass, decreased bone mineral density, sarcopenic obesity, and long-term cardiometabolic risk. This narrative review critically summarizes current evidence on multimodal exercise and nutritional interventions in pediatric oncology, with particular attention to their effects on physical function, body composition, nutritional status, and metabolic health. Literature searches were conducted in PubMed, Scopus, and Web of Science up to April 2026, combining contextual evidence with studies evaluating combined exercise and nutritional strategies. Current evidence suggests that structured and supervised exercise, particularly resistance and combined aerobic–resistance training, is feasible and safe, and may improve cardiorespiratory fitness, muscle strength, functional capacity, and body composition. Nutritional care should be individualized, prioritizing adequate protein intake, micronutrient status, periodic reassessment of energy requirements, and body composition rather than relying on BMI alone. Nevertheless, available findings remain limited by small sample sizes, heterogeneous protocols, variable supervision, inconsistent outcome assessment, and limited long-term follow-up. Integrating exercise, nutrition, and regular monitoring into pediatric oncology care may help mitigate treatment-related functional and metabolic complications. Future studies should prioritize adequately powered randomized trials, standardized intervention protocols, objective monitoring of exercise intensity, harmonized body composition and functional outcomes, and longer follow-up to define clinically applicable multimodal care models. Full article

Periodontitis is a biofilm-associated inflammatory disease that still requires effective local non-antibiotic antibacterial strategies. In this study, we developed a protonated defect-engineered atomic-layered graphitic carbon nitride nano-system (PVCN) for visible light photodynamic antibacterial therapy. Defect engineering was used to improve visible light absorption and photodynamic activity, while protonation introduced a positively biased surface potential to strengthen bacteria–material interactions and enhance interfacial antibacterial efficacy. Under visible light irradiation, PVCN showed increased ROS production, stronger bacterial adhesion, and rapid killing activity against both Staphylococcus aureus and Escherichia coli, with bactericidal efficiency above 95%. PVCN also disrupted S. aureus biofilms and induced membrane damage, intracellular content leakage, and metabolic suppression. Atomic force microscopy and omics analyses further supported enhanced bacterial adsorption as an important contributor to the improved antibacterial efficacy of PVCN. In vitro assays demonstrated preliminary cytocompatibility and hemocompatibility. In a ligature-induced mouse periodontitis model, PVCN reduced bacterial burden, alleviated inflammation, and attenuated alveolar bone loss. These results support PVCN as a promising photodynamic antibacterial material with preliminary therapeutic potential in experimental periodontitis, and highlight bio-interface regulation as a useful strategy for designing efficient carbon nitride-based photodynamic antibacterial materials. Full article

Osteoporosis and hyperglycemia are increasingly recognized as dual public health concerns in T1DM. However, the precise molecular mechanisms by which exercise ameliorates these conditions, particularly the contribution of mechanosensitive channels such as Piezo1, remain incompletely elucidated. To explore these mechanisms, T1DM mice were subjected to a 6-week treadmill training protocol (15 m/min, 20 min/day, 6 days/week) to evaluate the functions of exercise on diabetic osteoporosis and hyperglycemia. Exercise intervention markedly improved bone quality in T1DM mice, alleviating osteoporotic manifestations, as evidenced by enhanced mechanical strength, restored bone microarchitecture, and normalized histomorphology. Concurrently, exercise significantly reduced hyperglycemia. To clarify the role of Piezo1, mechanical stretch was applied to Piezo1-knockout MC3T3-E1 (Piezo1^−/−) cells in vitro, mimicking the mechanical stimulation induced by exercise. Consistent with the in vivo results, mechanical stimulation facilitated osteogenic differentiation and glucose metabolism through Piezo1-mediated mechanotransduction. Importantly, these beneficial effects were substantially abrogated in Piezo1^−/− cells, highlighting the central role of Piezo1. Collectively, these findings demonstrate that Piezo1-mediated mechanotransduction constitutes a critical factor by which exercise mitigates osteoporosis and hyperglycemia in T1DM mice. This study provides a framework for the development of new therapeutic strategies targeting Piezo1-mediated mechanotransduction for T1DM management. Full article

Background: Colorectal cancer is a common malignancy and 5-fluorouracil (FU) remains a mainstay of chemotherapy despite its toxicity. As an important part of comprehensive tumor treatment, dual-protein (DP) nutritional intervention is attracting more and more attention. Methods: This study preliminarily evaluated the regulatory effects of DP intervention on colorectal cells of CT26 tumor-bearing mice, examining the dosage and administration methods of DP, as well as the anti-tumor effects of FU alone or in combination with DP. Results: The results showed that low- and medium-dose DP numerically increased spleen index and showed trends toward alleviating FU-induced thymic atrophy, splenic damage, nephrotoxicity, and myocardial injury. It also partly mitigated muscle wasting, prevented FU-induced shortening of the colorectal tract, and reduced intestinal injury. In addition, DP was associated with increased lymphocyte, monocyte, and platelet counts and decreased granulocytes, suggesting possible alleviation of chemotherapy-induced bone marrow suppression and a potential effect on hematopoietic function. Flow cytometry results indicated possible effects of DP on CD4⁺ T and CD8⁺ T cell proliferation or apoptosis, modulation of effector and memory phenotypes, reduced splenic neutrophil levels, balanced B cell function, and maintained natural killer cell activity. In addition, DP intervention also showed trends toward regulating hepatic lipid metabolism and partially alleviating FU-induced dyslipidemia and muscle damage. In addition, DP and FU could increase IL-2, IL-10, GM-CSF and IFN-γ and decrease IL-6 and TNF-α. Conclusion: In conclusion, a moderate dose (0.67 g/kg) of DP had the most favorable trends, and the pre-intervention mode was more effective. This study also provided exploratory data on the potential of DP in reducing chemotherapy-related toxicity. These findings will provide preliminary scientific support for nutritional therapy in colorectal cancer patients, as well as for the research, development, and application of dual-protein foods for special medical purposes. Full article

Background: We previously reported that knocking down the ubiquitin E3 ligase LNX2 in bone marrow monocytes by shRNAs attenuated osteoclastogenesis in vitro. However, the role of LNX2 in the regulation of osteoclasts and bone homeostasis in vivo remains unknown. Methods: In this study, we generated myeloid Lnx2 conditional knockout mice by crossing Lnx2-flox mice with LysM-Cre mice. The role of LNX2 was verified through in vitro osteoclast induction experiments using mononuclear macrophages and experiments on estrogen-deficient osteoporosis models. Results: Micro-CT and histological analysis unveiled that loss of Lnx2 in osteoclast precursor cells decreased osteoclast numbers and increased trabecular bone mass in mice. Moreover, Lnx2 deficiency prevented bone loss in an ovariectomized mouse model of postmenopausal osteoporosis. In vitro mechanistic studies identified that the loss of Lnx2 had little effect on cell proliferation but significantly inhibited the formation of osteoclasts and bone resorption. Furthermore, the deletion of Lnx2 decreased the expression of NOTCH2 and its downstream HES1 via enhancing the level of the NOTCH2 inhibitor, NUMB. Conclusions: Our findings elucidate an important role of Lnx2 in the regulation of osteoclasts and bone metabolism and indicate that Lnx2 is a potential therapeutic target for the treatment of osteoporosis. Full article

Neuropathic pain remains a major clinical challenge due to its complex pathophysiology and limited treatment efficacy. Recent evidence suggests that vitamin D, beyond its classical role in bone and mineral metabolism, exerts neuroprotective and immunomodulatory effects that may influence pain perception. This review synthesizes current findings on the relationship between vitamin D status and neuropathic pain, highlighting potential mechanisms such as modulation of neuroinflammation, regulation of neuronal excitability, and influence on neurotransmitter pathways. Observational studies frequently report an association between vitamin D deficiency and increased pain severity, while interventional trials indicate that supplementation may alleviate neuropathic symptoms in specific populations. However, results remain heterogeneous, and mechanistic studies are still emerging. Understanding the interplay between vitamin D and neuropathic pain could open new avenues for adjunctive therapeutic strategies and personalized medicine approaches. Further high-quality clinical trials and mechanistic research are warranted to clarify causality and optimize clinical applications. Full article

The bark of Myrica rubra (Lour.) Siebold & Zucc (M. rubra) is a natural remedy widely used in China and other Asian countries to treat tissue and bone injuries, burns, scalds, gastrointestinal ulcers, and diarrhea. Myricanol is an important ingredient in the bark of M. rubra. This review summarizes articles published over the past 26 years on the pharmacological effects and mechanisms of action of myricanol, aiming to advance research and applications of myricanol. Evidence shows that myricanol has multiple bioactive properties, including antioxidant, anticancer, anti-inflammatory, antimicrobial, antidiabetic, and antihyperlipidemic effects. Myricanol improves metabolic abnormalities in mice by activating the AMPK/SIRT1/PGC-1α signaling pathway. It also demonstrates significant anticancer, antioxidant, and anti-inflammatory actions, primarily by regulating Caspase and BCL-2 family proteins, inhibiting iNOS expression, scavenging free radicals, and interacting with Peroxiredoxin 5. Therefore, myricanol shows great potential for the treatment of cancer, metabolic abnormalities, and inflammatory bowel disease. Further research is needed to improve its bioavailability, confirm its pharmacological effects and mechanisms in vivo, and explore its pharmacokinetic properties and safety. Full article

Background/Objectives: Plant-based diets are increasingly adopted by families with young children, yet their potential effects on bone development and metabolic regulation during early childhood remain insufficiently understood. This study aimed to evaluate body composition, bone mineral density (BMD), biochemical markers of bone turnover, and adipokine profiles in healthy children aged 5–6 years adhering to lacto-ovo-vegetarian or omnivorous diets. Methods: A cross-sectional analysis was conducted in a well-characterized cohort of 90 healthy normal-weight children consuming either lacto-ovo-vegetarian or omnivorous diets. Body composition and bone mineral density were measured using dual-energy X-ray absorptiometry, and circulating markers of bone formation, resorption, and adipokines were determined using ELISA methods. Correlation analyses were performed to examine the relationships between anthropometric variables, bone parameters, and adipokines. Results: No significant differences were observed between vegetarian and omnivorous diets in anthropometric characteristics, bone mineral content (BMC), or BMD, indicating comparable skeletal status. However, vegetarian children exhibited significantly higher levels of bone turnover markers, including bone alkaline phosphatase (BALP) (p = 0.023) and C-terminal telopeptide of type I collagen (CTX-I) (p = 0.035), and a lower osteocalcin OC/CTX-I ratio (p = 0.027). These findings may suggest a subtle imbalance in bone remodeling dynamics in these children, although their clinical significance remains uncertain. Additionally, higher levels of carboxylated osteocalcin (Gla-OC) (p = 0.022) and an increased carboxylated to undercarboxylated OC (Gla-OC/Glu-OC) ratio (p = 0.005) were observed in vegetarian children. Among adipokines, vegetarian children showed lower HMW adiponectin levels (p = 0.05) and a lower HMW/total adiponectin ratio (p = 0.012). Correlation analyses revealed distinct metabolic patterns between groups. In vegetarian children, bone parameters were primarily associated with lean mass, indicating the predominant role of mechanical factors in skeletal development. In contrast, omnivorous children demonstrated a more integrated relationship between bone indices and adipokines. Conclusions: In conclusion, while a lacto-ovo-vegetarian balanced diet supports normal bone mass in early childhood, it may be associated with subtle alterations in bone metabolism and its regulatory pathways, including adipokine profiles. These findings highlight the importance of adequate dietary planning and underscore the need for longitudinal studies to determine long-term effects on bone status. Full article

Background/Objectives: Serum 25-hydroxyvitamin D (25OHD) is a key determinant of calcium-phosphorus homeostasis and bone metabolism; however, its role as a modifier of the bone mineral density (BMD) response to romosozumab, a dual-action anabolic agent for osteoporosis, remains poorly characterized, particularly across different levels of renal function. This study investigated whether the renal function category and prior treatment history modified the association between baseline 25OHD and romosozumab BMD response. Methods: We conducted a retrospective cohort study of 315 consecutive Japanese patients treated with romosozumab (210 mg subcutaneously monthly for 12 months) at Mutsu General Hospital, Aomori, Japan (2019–2025; IRB approval RO7-5; date of approval: 20 January 2026). Patients were stratified by eGFR-based renal function category: preserved renal function (eGFR ≥ 60 mL/min/1.73 m², n = 199) and moderately reduced renal function (eGFR 30–59 mL/min/1.73 m², n = 86). Patients with severely reduced renal function (eGFR 15–29, n = 11) were excluded from the comparative analyses. Spearman rank correlations (Rs) were computed between baseline 25OHD and (i) baseline TRACP-5b and (ii) 12-month lumbar spine BMD changes. Mediation analysis was performed to examine TRACP-5b as a potential mediator. Results: In the preserved renal function group, baseline 25OHD was significantly and inversely correlated with TRACP-5b (Rs = −0.246, p = 0.0007). This correlation was absent in the moderately reduced renal function group (Rs = +0.036, p = 0.74), and the interaction was statistically significant (z = −2.38, p = 0.017). Among treatment-experienced patients, lower 25OHD levels were correlated with greater LS-BMD response (Rs = −0.197, p = 0.036), whereas no such correlation was observed in treatment-naïve patients (Rs = −0.009, p = 0.902). Mediation analysis did not identify TRACP-5b as a significant mediator. Conclusions: The association between serum 25OHD and romosozumab BMD response appears to be context-dependent across renal function categories and prior treatment history. These findings are hypothesis-generating and require prospective validation before they can be applied to clinical practice. Full article

Introduction: platelet-rich fibrin (PRF) is a second-generation platelet concentrate which is known for promoting cell migration, tissue repair, angiogenesis and bone formation. In contrast, the specific effects of trauma-activated PRF on mesenchymal stromal cells (MSC) are not yet fully understood. The present study investigates systemic effects of surgical trauma-activated PRF on MSCs in vitro, analyzing their metabolic activity, inflammatory responses, and regenerative capacity to optimize advanced treatment concepts for severe fractures and injuries. Material & Methods: PRF membranes (T-PRF from trauma patients, C-PRF from healthy controls) were generated. After co-incubation with MSC cells for 24, 72, and 120 h, further investigations of metabolic activity (MTT assay) and gene expression analyses were performed. Results: for MTT assay, results especially showed a significantly higher metabolic activity of T-PRF after 120 h. ELISA-results measuring cytokine levels (CXCL10, IL-6, VEGF, and IDO) exposed a frequent peak in T-PRF group at 72 h, declining slightly at 120 h. In the gene expression analyses, T-PRF exerted a comparatively stronger stimulating effect on MAPK14 and VEGFA after 24 h, while a decrease in gene expression for MAPK8, MAPK14, and RUNX2 was observed over time. Conclusion: surgical trauma-activated PRF seems to be a powerful inducer of early inflammatory and stress responses in MSCs with preserved angiogenic but limited osteogenic signaling. Therefore, a targeted balance between inflammatory activation and sustainable regeneration, as well as optimized preparation and possible combination with immunomodulatory approaches, appear to be crucial for the therapeutic success of PRF-based strategies. Full article

Periodontitis (PD) and rheumatoid arthritis (RA) are chronic inflammatory disorders that impose substantial individual and societal burdens worldwide. PD is characterized by progressive destruction of the periodontal ligament and alveolar bone, leading to tooth loss, impaired oral function, and sustained systemic inflammatory burden. RA, affecting approximately 0.5–1% of the population, is a chronic autoimmune disease marked by persistent synovial inflammation, progressive joint destruction, disability, and reduced quality of life. Increasing evidence indicates that these conditions are biologically and clinically interconnected. Both diseases share key pathogenic pathways, including microbial dysbiosis, immune dysregulation, chronic inflammation, genetic susceptibility, and aberrant autoantibody responses. Particular attention has focused on keystone periodontal pathogens such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, which may promote protein citrullination and the formation of anti-citrullinated protein antibodies (ACPA), thereby providing a plausible mechanistic bridge between periodontal infection and systemic autoimmunity. Shared genetic risk factors, including HLA-DRB1 susceptibility alleles, further support a common host predisposition. Clinical, epidemiological, and translational studies increasingly support a bidirectional association. Individuals with PD appear to have a higher risk of RA development, whereas patients with RA demonstrate greater prevalence, severity, and progression of periodontal disease. Interventional studies suggest that nonsurgical periodontal therapy may reduce local periodontal inflammation, circulating inflammatory biomarkers, and RA disease activity indices, while effective pharmacological control of RA may also improve periodontal outcomes. This narrative review critically evaluates the PD–RA relationship across four interconnected domains: (i) epidemiological and clinical associations between PD and RA, (ii) key mechanisms underlying RA pathogenesis, (iii) shared biological pathways linking both diseases, and (iv) the extent to which treatment of one condition influences the other. Particular emphasis is placed on major sources of heterogeneity and confounding—including smoking, metabolic comorbidities, disease stage, therapeutic exposure, and variable diagnostic definitions—that may explain inconsistencies across the literature. By integrating current mechanistic and clinical evidence, this review provides a structured synthesis that extends beyond a descriptive overview of association studies. A clearer understanding of the periodontal–rheumatologic axis may facilitate risk stratification, identify novel therapeutic targets, and support integrated multidisciplinary care. Targeting both oral and systemic inflammation may improve outcomes in patients with coexisting PD and RA and may potentially reduce the risk or severity of one condition in individuals already affected by the other. Full article

Bone grafting remains limited, and the strategies to design even more structurally complex scaffolds—able to reproduce the hierarchical architecture of bone extracellular matrix—are rapidly growing. In this study, we report the fabrication of a hierarchically structured scaffold produced by layering poly(ε-caprolactone)/gelatin (PCL/Gt) or poly(lactic acid)/gelatin (PLA/Gt) electrospun nanofibers via coaxial electrospinning onto 3D-printed poly(lactic acid) (PLA) scaffolds via fused deposition modeling (FDM). After the printing process, PLA disks (10 × 1 mm, 20% infill, ~80% porosity, pore size ~1.57 mm) were coated with core/shell (PCL/Gt, PLA/Gt) fibers to investigate the in vitro interfacial response of osteoblasts in comparison with monocomponent fibrous coatings (PCL, PLA, Gt). SEM and TEM confirmed that core/shell fibers exhibited bead-free morphologies, with a significant reduction in fiber diameter (≈287–316 nm) and higher interfibrillar porosity compared to monocomponent fibers. FTIR and thermogravimetric analyses indicated the presence of hydrogen bonding between the polyester and gelatin, and the absence of residual solvent after deposition. At the same time, water contact angle measurements confirmed an increase in hydrophilic properties from 80–86° to 120° ascribable to the presence of gelatin. Accordingly, in vitro response of human fetal osteoblasts (hFOB 1.19) exhibited an evident improvement in the case of Gt-based fibrous coatings (i.e., PCL/Gt and PLA/Gt) in terms of early adhesion (4–24 h) and metabolic activity from 3 to 21 days, cell spreading into star-shaped morphologies, formation of extracellular matrix, and mineral phase deposition. In more detail, a remarkable increase in alkaline phosphatase activity was observed in Gt-based coaxial coatings from day 7 onward, with the highest values recorded for PLA/Gt. Overall, we demonstrated that the Gt-based coaxial fibrous coating provided a mix of topological and biochemical cues that synergistically promoted key osteoblast activities at the interface, supporting the regeneration of new bone tissue in highly tailored 3D-printed scaffolds, thus suggesting a promising strategy for personalized regenerative medicine. Full article

Background: Growth disorders, including central precocious puberty and delayed puberty, can significantly affect linear growth, skeletal maturation, metabolic regulation, and psychosocial development during childhood and adolescence. This systematic review synthesizes the current evidence regarding the effectiveness and safety of hormone-based therapies used in children with disorders of pubertal maturation. Methods: A PRISMA-guided systematic search was carried out between January 2016 and March 2026 in different databases, such as MEDLINE (PubMed), EMBASE, CENTRAL, Scopus, Web of Science, CINAHL, LILACS and OpenGrey; the protocol was previously registered in the PROSPERO database (CRD420251068048). Non-randomized, randomized controlled trials and observational research including participants aged 0–18 years receiving hormone therapies were eligible. Risk of bias was assessed using validated, design-specific tools. Results: Twenty studies involving 21,812 participants were included. GnRHa therapy improved final adult height (+3.5 to +4.5 cm) and reduced bone age advancement (−0.6 to −1.3 years) in children with central precocious puberty. rhGH therapy increased growth velocity (+3.0 to +5.0 cm/year) and height SDS (+0.3 to +0.9), particularly in idiopathic short stature and Prader–Willi syndrome. Combined GnRHa plus rhGH therapy showed greater short-term growth benefits than GnRHa alone. Both therapies showed favorable safety profiles, with predominantly mild adverse events and discontinuation rates below 2%. However, the evidence was limited by substantial heterogeneity and moderate-to-serious risk of bias. Conclusions: GnRHa and rhGH therapies are generally effective and safe for improving growth and pubertal outcomes in pediatric endocrine disorders. However, further long-term studies are needed to clarify their metabolic and psychosocial effects in adulthood. Nevertheless, these conclusions should be interpreted with caution due to the study’s moderate-to-serious risk of bias and heterogeneity. Full article

Palmitic acid (PA), the most abundant saturated fatty acid in the human body, is implicated in lipotoxicity under hyperlipidemic conditions, with potential consequences for bone metabolism. To investigate its impact on developing bone tissue, this study used an ex vivo organotypic embryonic chick femur model, exposing femora to control (0 µM), low (50 µM), and high (200 µM) PA concentrations. A multimodal approach, integrating microtomographic, histochemical, ultrastructural, and gene expression analyses, was used to assess tissue architecture, matrix composition, mineralization, and molecular adaptations. PA exposure significantly reduced longitudinal femoral growth, as evidenced by decreased femoral length and tissue volume. Gene expression analysis revealed reduced expression of selected osteogenic differentiation-related markers, including RUNX2, BMP2, and SPP1. However, COL1A2 expression was upregulated, correlating with increased collagenous matrix deposition and enhanced mineralization in PA-treated groups. Alcian blue staining further suggested reduced proteoglycan-rich cartilage matrix, particularly at 200 µM PA. Additionally, PA modulated the expression of both pro-inflammatory and anti-inflammatory mediators, along with increased autophagy-associated responses, as suggested by the upregulation of autophagy-related genes and the presence of autophagosomes and autolysosomes. These findings indicate that PA does not simply exert a deleterious effect on bone tissue but rather redirects the developmental trajectory of the organotypic femur by reducing longitudinal growth while promoting collagen-rich matrix maturation and mineral compaction. This response may involve altered cartilage-associated endochondral processes, fatty-acid-driven metabolic adaptation, osteoblast/osteocyte maturation, and autophagy-associated matrix processing under lipid-enriched conditions. Full article

Anterior cruciate ligament reconstruction relies on interference screw fixation, yet insufficient graft osseointegration remains a critical clinical challenge. This study aimed to develop and characterize a 3D-printed polymeric–hydroxyapatite composite interference screw with an osteoinductive surface to enhance localized osteogenic responses. Screws were designed, modeled, and fabricated using fused deposition modeling 3D printing with a polycaprolactone-poly(lactic-co-glycolic acid)-hydroxyapatite composite. Physico-chemical characterization was performed using scanning electron microscopy. Biocompatibility was assessed through mesenchymal stem cell metabolic activity assays and morphological analysis. Osteogenic gene expression was quantified by RT-qPCR following culture in osteogenic differentiation medium. In vivo osseointegration was evaluated histologically at five and nine weeks following implantation in the proximal tibial epiphysis of a rat model. 3D printing successfully produced screws with consistent geometry and surface characteristics. The composite material supported robust mesenchymal stem cell proliferation without cytotoxicity or morphological abnormalities. Histological examination revealed progressive bone formation with no adverse tissue reactions, including the absence of cyst formation, osteolysis, or excessive fibrosis. RT-qPCR revealed upregulation of osteogenic markers in those enhanced screws. These results indicate that the 3D-printed polymeric–hydroxyapatite composite screws are biocompatible and capable of stimulating localized osteogenic activity, supporting their potential as a biological foundation for future evaluation in anterior cruciate ligament reconstruction applications. Full article