Search Results (2,466)

Dietary supplementation with functional nutrients is a safe strategy to improve bone health. This study aimed to investigate the ameliorative effects of Berberine (BBR) on dexamethasone-induced bone loss in mice and its potential mechanisms. Micro-CT, histological staining, ELISA and Western blot were employed to evaluate BBR’s skeletal benefits; 16S rRNA sequencing, serum metabolomics and correlation analysis were used to explore its regulatory mechanisms. In vivo experiments showed that BBR improved bone mineral density and trabecular microarchitecture, and upregulated osteogenic markers (COL1 and BMP2). Intestinal bacterial sequencing showed that BBR altered gut bacterial composition, increasing the abundance of Desulfovibrio and Bacteroides while decreasing opportunistic pathogens. BBR also modulated bacterial richness, evenness, and community stability. Serum metabolomics identified 107 BBR-reversed differential metabolites; of these, 33.64% were lipids and lipid-like molecules, which were mainly involved in glycerophospholipid metabolism. Further correlation analysis revealed that BBR-enriched Desulfovibrio was linked to pathway R04864, producing a key glycerophospholipid metabolite positively correlated with bone mass parameters. Overall, these findings suggest that the attenuation of bone loss by BBR may be associated with alterations in the gut microbiota–glycerophospholipid metabolic axis, supporting its potential as a functional food ingredient for bone health. Full article

In a previous study, we demonstrated that a novel surface treatment applied to laser-melted Ti6Al4V substrates supports osteoblast-like cell adhesion, proliferation, and the activation of early osteogenic pathways. Building on these preliminary findings, the present work aimed to further investigate the ability of the same surface to promote extracellular matrix (ECM) deposition, organization, and osteogenic maturation, which are critical events for the establishment of a stable bone–implant interface in subperiosteal dental implants. Human osteoblast-like MG-63 cells were cultured on Ti6Al4V discs subjected to different surface treatments, including a proprietary surface modification (ATcs) specifically designed for subperiosteal applications. ECM formation and maturation were evaluated through scanning electron microscopy coupled with energy-dispersive spectroscopy, immunofluorescence, and semiquantitative analyses of osteogenic markers type I collagen (COL1A1), secreted protein acidic and rich in cysteine (SPARC), and dentin matrix protein 1 (DMP1) through Western blotting. The results showed that, while all tested surfaces supported cell adhesion, the ATcs surface promoted a distinct osteogenic profile characterized by enhanced DMP1 expression, organized collagen deposition, and the formation of calcium–phosphate–rich mineralized structures. Compared to surfaces that primarily stimulated cell proliferation or early matrix production, ATcs appeared to favour progression toward late-stage osteogenic maturation and matrix mineralization. Taken together, these findings extend our previous observations and indicate that this novel surface treatment not only supports osteoblast viability and early differentiation but also promotes extracellular matrix maturation, a key prerequisite for effective osseointegration. Although further in vivo studies are required, the present data provide additional biological rationale for the use of ATcs-treated Ti6Al4V surfaces in next-generation custom-made subperiosteal implant designs. Full article

Introduction: Inflammatory and immune-based prognostic markers such as the Lung Immune Prognostic Index (LIPI) and the Glasgow Prognostic Score (GPS) have gained increasing attention in ES-SCLC, particularly in patients receiving first-line chemoimmunotherapy. However, no prior study has explored a broader, integrated inflammatory framework that evaluates these parameters collectively. Methods: We retrospectively evaluated 166 patients with ES-SCLC treated with first-line platinum–etoposide plus atezolizumab or durvalumab between 2019 and 2025. LIPI could be calculated in 123 patients based on available dNLR and LDH values, while GPS and the Combined Inflammatory Prognostic Score (CIPS) could be assessed in 120 patients with accessible CRP and albumin data. Results: Median PFS and OS were 8.16 and 15.96 months, respectively. In univariate analyses, poor ECOG PS, liver and bone metastases, poor LIPI, poor GPS, and high-risk CIPS were associated with shorter PFS and OS. In multivariate analysis, only LIPI and GPS remained independent predictors of both PFS and OS, while ECOG PS was independently associated with OS. Although CIPS demonstrated clear prognostic separation in univariate analysis, it did not retain independent significance, likely due to sample size limitations and overlap with LIPI and GPS components. Conclusions: LIPI and GPS are strong independent prognostic markers in ES-SCLC receiving chemoimmunotherapy. While CIPS did not demonstrate independent prognostic value in multivariate analysis, its simplicity, balanced two-tier design, and use of routinely available biomarkers highlight its potential clinical utility. To our knowledge, this is the first study to assess a combined inflammatory prognostic model in this population. Prospective multicenter validation is warranted. Full article

Bone formation requires a substantial energy supply to sustain extracellular matrix production and mineralization, yet the temporal contribution of lipid metabolism during osteoblast maturation remains incompletely characterized. This study investigated the molecular and transcriptional remodeling of lipid metabolism. Intracellular lipid distribution was analyzed by confocal microscopy using Nile Red staining. Transcriptional modulation of lipid synthesis, storage, lipolysis, genes associated with mitochondrial fatty acid oxidation, and osteogenic markers were assessed by quantitative real-time PCR, and the biochemical composition was evaluated by Raman spectroscopy. Early stages of spheroid development showed higher expression of genes involved in lipid synthesis and storage (FASN, DGAT2, and PLIN2) together with intracellular lipid accumulation, whereas later stages displayed increased expression of lipolytic and β-oxidation markers (PNPLA2/ATGL, CPT1A, and HADHA), accompanied by the redistribution of lipid droplets. The Raman analysis revealed a time-dependent variation of lipid-associated CH₂/CH₃ bands and modulation of protein-related Amide I–III signals, consistent with biochemical remodeling during maturation. Overall, the data indicate a coordinated transcriptional shift from lipid accumulation-associated pathways toward lipid mobilization during osteogenic progression in a 3D culture. This model provides a controlled experimental platform for investigating metabolic regulation during bone formation and for studying metabolic alterations associated with skeletal disorders. Full article

Titanium implants are widely used in orthopedic and dental fields but often face challenges such as insufficient osseointegration and peri-implant inflammation. While Strontium (Sr) possesses potent bioactive properties, achieving its controlled delivery at the implant-tissue interface remains technically challenging. To address this, we engineered a multidimensional composite coating by constructing a micro/nano-porous TiO₂ substrate via micro-arc oxidation (MAO), followed by polydopamine (PDA)-assisted Sr immobilization. This integrated architecture significantly enhanced surface hydrophilicity and facilitated high-content Sr loading with sustained release kinetics. Biological evaluations demonstrated that the PDA-mediated interface promoted superior initial adhesion and spreading of bone marrow mesenchymal stem cells (BMSCs), synergizing with released Sr²⁺ to markedly upregulate core osteogenic markers (Runx2, ALP). Crucially, the functionalized surface actively optimized the immune microenvironment by inducing M1-to-M2 macrophage polarization and comprehensively suppressing RANKL-induced osteoclastogenesis via the downregulation of TRAP and DC-STAMP. By integrating these pro-osteogenic, anti-inflammatory, and anti-resorptive capabilities, this tri-functional system effectively rebalances the bone remodeling microenvironment. Consequently, it provides a robust, universally applicable strategy for enhancing the therapeutic efficacy of next-generation orthopedic and dental implants. Full article

Background: Extracranial metastasis (EM) from glioblastoma (GB), IDH-wildtype (WHO CNS 2021 grade 4) is rare and often under-recognized, yet it has immediate implications for staging and management. We report a case series integrating advanced neuroimaging, whole-body imaging, and pathology/biomarkers to characterize imaging–pathology correlates of EM and highlight practical clinical triggers that should prompt systemic evaluation. Case presentation: We report three patients with adult-type, IDH-wildtype GB who developed EM confirmed by cytology/histology and/or concordant multimodality imaging. Brain MRI (1.5T/3T) demonstrated aggressive primary tumors with qualitative elevation of DSC-perfusion and frequent tumor–surface contact (dural, ependymal/leptomeningeal contact). Intratumoral susceptibility signal reached grade 3 where assessed. All patients underwent surgical resection followed by temozolomide-based chemoradiation; two received fotemustine and bevacizumab, and one underwent re-irradiation. EM presented with clinical triggers including severe axial/back pain, palpable cervical masses, and/or cytopenias. Initial EM sites were bone marrow/vertebrae (n = 1) and cervical lymph nodes (n = 2); staging revealed additional osseous disease in both nodal cases and a small pulmonary nodule in one. Nodal and osseous lesions were FDG-avid on 18F-FDG PET/CT. OLIG2-positive cytology confirmed cervical nodal metastases, and bone marrow aspiration with GFAP/OLIG2 positivity confirmed medullary infiltration. All tumors shared a molecular profile of TERT-promoter mutation, ATRX wild-type, TP53 mutation, and MGMT-promoter methylation. Despite attempts at second- and third-line therapies, disease progression was rapid, and all patients succumbed within 8–16 months of diagnosis. Discussion: This series underscores that EM can occur despite MGMT-promoter methylation and supports the concept of heterogeneous metastatic phenotypes in GB. Our cases reinforce that new axial/back pain or hematologic abnormalities may signal osseous or marrow involvement, and necrotic cervical lymphadenopathy in GB patients warrants dedicated imaging and tissue confirmation with glial markers. Integrating brain MRI features (high perfusion, surface contact, susceptibility burden) with FDG-PET/CT and targeted cytology/pathology can expedite diagnosis and inform multidisciplinary care. Conclusions: EM can arise despite MGMT-promoter methylation in IDH-wildtype GBM. Imaging red flags (high perfusion, surface contact, necrotic/FDG-avid cervical nodes) and clinical cues (axial pain, cytopenias, neck masses) should prompt early systemic staging (CT/PET-CT) and targeted tissue confirmation to advance management. Full article

Background and Objectives: The contribution of body composition to muscle weakness and physical performance in older adults remains incompletely defined. This study aimed to evaluate the discriminative capacity of total and segmental body composition variables to identify muscle weakness and low physical performance in older adults. Materials and Methods: A cross-sectional study was conducted in 268 community-dwelling older adults (72.2 ± 8.2 years; 81.3% women). Body composition (lean mass, fat mass, and bone mineral content [BMC], total and segmental) was assessed using dual-energy X-ray absorptiometry. Muscle weakness was assessed by handgrip strength (≤27 kg in men; ≤16 kg in women), and low physical performance by the Short Physical Performance Battery ≤8. Sex-stratified receiver operating characteristic (ROC) analyses were performed. Results: No significant differences were found between sexes for age (p = 0.307) or body mass index (p = 0.892). However, men exhibited significantly higher waist circumference (105.2 ± 11.9 vs. 97.8 ± 12.4 cm; p < 0.001) and handgrip strength (30.3 ± 6.8 vs. 18.3 ± 4.6 kg; p < 0.001) than women. Regarding body composition, men presented higher total lean mass (50.4 ± 6.9 vs. 37.2 ± 4.6 kg; p < 0.001) and total bone mineral content (2666 ± 483 vs. 1940 ± 286 g; p < 0.001). Conclusions: Body composition variables showed higher discriminative capacity for muscle weakness than for low physical performance. The ability of lean mass and BMC to identify low physical performance was modest in both sexes, suggesting that structural body composition variables alone may be insufficient to discriminate complex functional impairment in older adults. Full article

Background: Cutaneous radiation injury arises when ionizing radiation disrupts epidermal barrier integrity, triggering persistent DNA damage, oxidative stress, and senescence-associated inflammatory signaling that drive extracellular matrix degradation and impaired regeneration. Clinical burden is rising due to dose-intensified radiotherapy, but also due to an increased use of energy-based aesthetic procedures that elicit radiation-like dermal injury. Dermal fibroblasts exhibit marked sensitivity to ionizing radiation and rapidly acquire senescence-associated secretory phenotypes that suppress collagen biosynthesis and promote chronic inflammation, underpinning the need for regenerative treatments that restore tissue homeostasis and regenerative competence. Mesenchymal stem cell–derived exosomes have emerged as a promising therapeutic strategy in this setting, with increasing preclinical evidence demonstrating their capacity to attenuate oxidative stress, enhance DNA damage-repair pathways, and normalize fibroblast metabolic function. Methods: In this study, we examine the expression profiles for 14 radiation response–associated genes of irradiated human dermal fibroblasts that were treated with bone marrow and umbilical cord MSC-derived exosomes at different timepoints using quantitative RT-PCR analysis. We also explore functional relationships among these genes through interaction network analysis, and outline a framework to organize pathway-level transcriptional responses to irradiation and exosome treatment. Results: MSC-derived exosome treatment was associated with attenuated early damage response signaling at 24 h, followed by increased expression of genes associated with DNA repair and oxidative stress recovery at intermediate timepoints. Exosome-treated cells also exhibited transcriptional changes consistent with modulation of cell-cycle regulatory pathways and reduced expression of pro-inflammatory markers by 5 d. These findings suggest that MSC-derived exosomes influence the temporal organization of the fibroblast transcriptional response to ionizing radiation and may contribute to molecular programs associated with tissue recovery following ionizing radiation exposure. Full article

Endoscopic sinus surgery (ESS) is commonly performed to treat chronic rhinosinusitis and selected sinonasal tumors, yet postoperative complications such as neo-osteogenesis and restenosis remain frequent, largely due to impaired mucosal regeneration after extensive epithelial and bony tissue loss. Successful nasal epithelial repair requires a microenvironment that preserves cell viability, phenotype, and barrier integrity. Conventional culture substrates often lack physiological relevance or rely on animal-derived components, limiting translational applicability. In this study, we evaluated nanofibrillar cellulose (NFC) hydrogel (GrowDex^®) as a xeno-free scaffold for primary human nasal epithelial cells (NECs). NECs isolated from healthy donor tissue were characterized by immunofluorescence and qPCR for basal, goblet, and ciliated cell markers. Cells embedded in NFC were assessed for viability, cytotoxicity, epithelial morphology, and barrier function. Transepithelial electrical resistance (TEER) and FITC-dextran permeability assays were used to quantify barrier integrity and compared with collagen- and polylysine-based controls. NECs cultured in NFC maintained high viability, stable epithelial morphology, and preserved subtype-specific marker expression without detectable cytotoxicity. NFC-supported cultures demonstrated enhanced barrier formation, indicated by higher TEER values and reduced paracellular permeability relative to controls, and sustained structural integrity during extended culture. These findings identify NFC hydrogel as a biocompatible, non-animal scaffold that supports functional human nasal epithelium regeneration and may contribute to advanced tissue engineering strategies for craniofacial bone repair. Full article

Accurate radiation biodosimetry is urgently needed for medical management after large-scale radiation exposure. Partial-body irradiation with 5% bone marrow sparing (PBI/BM5) provides a realistic radiation model. The current study specifically focused on the high-dose lethality window (12–16 Gy), where survival transitioned from 100% to 0%, representing a clinically distinct and underserved scenario requiring dedicated biodosimetry tools. We defined the survival profile of male C57BL/6 mice after PBI/BM5 and found that doses of 13.5–14.0 Gy were nonlethal within 12 days, whereas 15.0–15.5 Gy caused 100% mortality within 12 days, with a calculated LD_50/12 of 14.68 Gy. A separate cohort of 14.0 Gy showed 100% survival up to 90 days post-radiation. To develop serum cytokine-based biodosimetry in high-dose radiation exposure, mice were exposed to 12.0–16.0 Gy PBI/BM5, and serum was collected on days 1, 3, and 7. A multiplex cytokine assay was used to quantify 70 total cytokines/chemokines. After the exclusion of 4 targets outside detection limits, 66 markers were utilized for downstream analysis. PCA, clustering and heatmaps, and LASSO classification revealed that cytokine signatures can classify radiation groups/status/doses. A 4-cytokine panel (IL-7, GDF-15, IL-16 and FLT3L) could distinguish naïve vs. irradiated mice on all study days. A 24-cytokine signature panel distinguished radiation survivors vs. non-survivors, and another 34-cytokine panel separated radiation doses (12–16 Gy); the prediction was better on day 7 compared to earlier time points. This exploratory study was specifically designed to define the systemic inflammatory response in a high-dose window where survival transitions from 100% to 0% (the ‘lethality threshold’) in a clinically relevant partial-body irradiation model. These findings show that serum cytokines have strong potential for high-dose triage, survival prediction, and dose discrimination within the near-lethal exposure range in a clinically relevant PBI/BM5 model. Extension to lower dose ranges is an important direction for future work. Full article

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, with most cases arising from B-cell precursors expressing the CD19 marker. CD19 negativity in B-lineage ALL (B-ALL) is very rare de novo and poses diagnostic and therapeutic challenges. Sometimes, de novo CD19-negative B-ALL is associated with hypercalcemia, which is a potentially life-threatening metabolic disorder in children, rarely occurring in cancers. Most often it is reported in solid tumors, and few cases are reported in pediatric acute leukemia. CD19-negative B-ALL relapse is also an increasing dramatic event, secondary to immunotherapy. We describe a ten-month-old infant presenting with hypercalcemia, anemia, and osteolytic bone lesions. Bone marrow analysis revealed CD10-positive and CD19-negative B-ALL. The patient achieved complete remission but later experienced two relapses and died of respiratory failure after a second allogeneic hematopoietic stem cell transplantation (HSCT). Only nine cases of de novo CD19-negative B-ALL have been reported so far. Many are associated with hypercalcemia and osteolytic lesions. However, here we highlight the clinical impact of the more common secondary form of CD19-negative B-ALL as a relapse of CD19-positive ALL, right after the administration of targeted immunotherapy. Full article

Background/Objectives: Early-life skeletal growth is critical for achieving optimal peak bone mass. This study aimed to investigate whether synbiotic supplementation with 2′-fucosyllactose (2′-FL) and Lactiplantibacillus plantarum Hi188 (Hi188) influences bone development in growing mice and its potential association with gut microbial modulation. Methods: Three-week-old BALB/c mice were orally supplemented with 2′-FL, Hi188, or their combinations at low and medium doses for 7 weeks. Bone length, microarchitecture and mechanical properties were analyzed. Serum bone turnover markers and osteogenic gene expression were analyzed by ELISA and qRT-PCR, respectively. Gut microbiota composition, and short-chain fatty acid (SCFA) production were analyzed by 16S-rRNA sequencing and GC-FID, respectively. Correlation associations among microbial taxa, SCFAs, and skeletal parameters were also assessed. Results: Medium-dose synbiotic supplementation significantly increased tibial and spine length without altering body weight or intestinal histology. Trabecular bone density and volume fraction were elevated, accompanied by reduced trabecular separation and improved mechanical strength. Serum BALP levels were increased and TRACP-5b levels were reduced, together with upregulation of osteogenesis- and matrix-related genes. Synbiotic treatment also modulated gut microbial composition, enriched SCFA-associated taxa, and significantly enhanced total and individual SCFA levels. Correlation analyses revealed selective associations among specific microbial taxa, SCFAs, and skeletal structural and molecular parameters. Conclusions: Medium doses of synbiotic supplementation were associated with improved skeletal growth and bone quality during development, alongside coordinated modulation of bone remodeling and gut microbial metabolic activity. These findings suggest its potential as a functional nutritional strategy for supporting early bone health. Full article

Postmenopausal osteoporosis is an age-related condition in which estrogen deficiency drives low-grade inflammation and oxidative stress, disrupting the homeostatic balance between bone formation and resorption. Since osteopenia represents a critical intermediate stage, preventive strategies are essential to mitigate its progression. Preclinical studies suggest that hydrogen sulfide (H₂S), a gaseous mediator with antioxidant properties, protects bone metabolism by supporting osteoblast function and suppressing osteoclast activity. Building on this evidence, we conducted the first exploratory clinical trial assessing the effects of inhalation therapy with sulfurous mineral waters on systemic biomarkers in postmenopausal women with osteopenia. Thirty-eight eligible participants underwent a daily inhalation of sulfurous waters (14.6 mg/L sulfide) for 12 consecutive days. Biomarkers of oxidative stress, inflammation, and bone turnover were assessed at baseline, immediately post-treatment, and five days after cessation in the serum of patients. The treatment was well tolerated and did not cause any early adverse effect. Serum H₂S levels, measured in a subset of participants, significantly increased, confirming systemic bioavailability. Sulfurous water inhalation induced a marked change in oxidative stress, with malondialdehyde levels declining by up to 37% from baseline. Pro-inflammatory cytokines, particularly IL-8 and MIP-1α, were significantly decreased (up to 50–70%) at the end of the treatment. Reference bone turnover markers P1NP and CTX-1 did not show significant changes; however, BALP exhibited a significant increase, suggesting the activation of pathways linked to biomineralization. These findings provide preliminary human evidence that inhaled sulfurous waters enhance systemic H₂S bioavailability and modulate redox and inflammatory pathways associated with bone remodeling in osteopenic women, supporting the rationale for further controlled pharmacodynamic investigations evaluating the potential of H₂S in bone health. Full article

Background/Objectives: Osteoarthritis is a chronic joint disorder involving the progressive breakdown of articular cartilage, which leads to joint pain and impaired mobility. The present study investigated the effects of curcuminoids phospholipid (CP) on osteoarthritis progression, assessed its cartilage-protective effects, and elucidated the underlying mechanisms. Methods: Male Sprague–Dawley rats were randomly allocated to six experimental groups. One group received an intra-articular saline injection as the normal control (NC), while the remaining five groups were injected with monosodium iodoacetate (MIA) and consisted of an MIA control group (MC), a positive control group treated with celecoxib (PC, 3 mg/kg), and three groups treated with CP (31.25, 62.5, or 125 mg/kg). Results: Compared with the MC group, CP administration significantly improved pain-related behavior, as assessed by weight-bearing measurements. Micro-computed tomography and histological analyses demonstrated that CP administration mitigated subchondral bone erosion and preserved cartilage integrity. Additionally, the CP treatment significantly reduced markers associated with cartilage degradation, including matrix metalloproteinases and cartilage oligomeric matrix proteins; downregulated the expression of matrix-degrading enzymes; and restored aggrecan expression. Serum levels of inflammatory mediators, including nitric oxide; prostaglandin E₂; C-reactive protein; and pro-inflammatory cytokines, including interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β, were reduced following CP administration. Furthermore, CP decreased the activation of nuclear factor kappa B (NF-κB) signaling. Conclusions: These findings suggest that CP may be a promising functional agent for osteoarthritis, demonstrating beneficial effects on pain-related outcomes and cartilage integrity, potentially mediated by its anti-inflammatory activity. Full article