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Background: The comprehensive management of diabetic bone defects remains a substantial clinical challenge due to the hostile regenerative microenvironment characterized by aggravated inflammation, excessive reactive oxygen species (ROS), bacterial infection, impaired angiogenesis, and unbalanced bone homeostasis. Thus, an advanced multifunctional therapeutic platform capable of simultaneously achieving immune regulation, bacterial elimination, and tissue regeneration is urgently designed for augmented bone regeneration under diabetic pathological milieu. Methods and Results: Herein, a photoactivated soft-hard combined scaffold system (PGCZ) was engineered by introducing polydopamine-modified zeolitic imidazolate framework-8-loaded double-network hydrogel (soft matrix component) into 3D-printed poly(ε-caprolactone) (PCL) scaffold (hard matrix component). The versatile PGCZ scaffold based on double-network hydrogel and 3D-printed PCL was thus prepared and features highly extracellular matrix-mimicking microstructure, suitable biodegradability and mechanical properties, and excellent photothermal performance, allowing long-term structural stability and mechanical support for bone regeneration. Under periodic near-infrared (NIR) irradiation, the localized photothermal effect of PGCZ triggers the on-demand release of Zn2+, which, together with repeated mild hyperthermia, collectively accelerates the proliferation and osteogenic differentiation of preosteoblasts and potently inhibits bacterial growth and biofilm formation. Additionally, the photoactivated PGCZ system also presents outstanding immunomodulatory and ROS scavenging capacities, which regulate M2 polarization of macrophages and drive functional cytokine secretion, thus leading to a pro-regenerative microenvironment in situ with enhanced vascularization. In vivo experiments further demonstrated that the PGCZ platform in conjunction with mild photothermal therapeutic activity remarkably attenuated the local inflammatory cascade, initiated endogenous stem cell recruitment and neovascularization, and orchestrated the osteoblast/osteoclast balance, ultimately accelerating diabetic bone regeneration. Conclusions: This work highlights the potential application of a photoactivated soft-hard combined system that provides long-term biophysical (mild photothermal stimulation) and biochemical (on-demand ion delivery) cues for accelerated healing of diabetic bone defects.
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Regeneração Óssea , Hidrogéis , Terapia Fototérmica , Alicerces Teciduais , Animais , Camundongos , Regeneração Óssea/efeitos dos fármacos , Terapia Fototérmica/métodos , Alicerces Teciduais/química , Hidrogéis/química , Indóis/química , Indóis/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Impressão Tridimensional , Osteogênese/efeitos dos fármacos , Poliésteres/química , Diabetes Mellitus Experimental/terapia , Masculino , Ratos , Polímeros/química , Espécies Reativas de Oxigênio/metabolismo , Cicatrização/efeitos dos fármacos , AngiogêneseRESUMO
The treatment of bone defects remains a substantial clinical challenge due to the lack of spatiotemporal management of the immune microenvironment, revascularization, and osteogenic differentiation. Herein, deferoxamine (DFO)-loaded black phosphorus nanosheets decorated by polydopamine layer are prepared (BPPD) and compounded into gelatin methacrylate/sodium alginate methacrylate (GA) hybrid hydrogel as a smart-responsive therapeutic system (GA/BPPD) for accelerated bone regeneration. The BPPD nanocomposites served as bioactive components and near-infrared (NIR) photothermal agents, which conferred the hydrogel with excellent NIR/pH dual-responsive properties, realizing the stimuli-responsive release of DFO and PO4 3 - during bone regeneration. Under the action of NIR-triggered mild photothermal therapy, the GA/BPPD hydrogel exhibited a positive effect on promoting osteogenesis and angiogenesis, eliminating excessive reactive oxygen species, and inducing macrophage polarization to the M2 phenotype. More significantly, through macrophage M2 polarization-induced osteoimmune microenvironment, this hydrogel platform could also drive functional cytokine secretion for enhanced angiogenesis and osteogenesis. In vivo experiments further demonstrated that the GA/BPPD system could facilitate bone healing by attenuating the local inflammatory response, increasing the secretion of pro-healing factors, stimulating endogenous cell recruitment, and accelerating revascularization. Collectively, the proposed intelligent photothermal hydrogel platform provides a promising strategy to reshape the damaged tissue microenvironment for augmented bone regeneration.
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Osteogênese , Terapia Fototérmica , Regeneração Óssea , Hidrogéis , MetacrilatosRESUMO
BACKGROUND AND OBJECTIVES: Negative surgical margins are significant in improving patient outcomes. However, surgeons can only rely on visual and tactile information to identify tumor margins intraoperatively. We hypothesized that intraoperative fluorescence imaging with indocyanine green (ICG) could serve as an assistive technology to evaluate surgical margins and guide surgery in bone and soft tissue tumor surgery. METHODS: Seventy patients with bone and soft tissue tumors were enrolled in this prospective, non-randomized, single-arm feasibility study. All patients received intravenous indocyanine green (0.5 mg/kg) before surgery. Near-infrared (NIR) imaging was performed on in situ tumors, wounds, and ex vivo specimens. RESULTS: 60/70 tumors were fluorescent at NIR imaging. The final surgical margins were positive in 2/55 cases, including 1/40 of the sarcomas. Surgical decisions were changed in 19 cases by NIR imaging, and in 7/19 cases final pathology demonstrated margins were improved. Fluorescence analysis showed that the tumor-to-background ratio (TBR) of primary malignant tumors was higher than that of benign, borderline, metastatic, and tumors ≥5 cm in size had higher TBR than those <5 cm. CONCLUSIONS: ICG fluorescence imaging may be a beneficial technique to assist in surgical decision making and improving surgical margins in bone and soft tissue tumor surgery.
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Verde de Indocianina , Neoplasias de Tecidos Moles , Humanos , Margens de Excisão , Estudos Prospectivos , Imagem Óptica/métodos , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/cirurgia , Tomada de DecisõesRESUMO
(1) Background: Biopsies are the gold standard for the diagnosis of musculoskeletal tumors. In this study, we aimed to explore whether indocyanine green near-infrared fluorescence imaging can assist in the biopsy of bone and soft tissue tumors and improve the success rate of biopsy. (2) Method: We recruited patients with clinically considered bone and soft tissue tumors and planned biopsies. In the test group, indocyanine green (0.3 mg/kg) was injected. After identifying the lesion, a near-infrared fluorescence camera system was used to verify the ex vivo specimens of the biopsy in real time. If the biopsy specimens were not developed, we assumed that we failed to acquire lesions, so the needle track and needle position were adjusted for the supplementary biopsy, and then real-time imaging was performed again. Finally, we conducted a pathological examination. In the control group, normal biopsy was performed. (3) Results: The total diagnosis rate of musculoskeletal tumors in the test group was 94.92% (56/59) and that in the control group was 82.36% (42/51). In the test group, 14 cases were not developed, as seen from real-time fluorescence in the core biopsy, and then underwent the supplementary biopsy after changing the puncture direction and the location of the needle channel immediately, of which 7 cases showed new fluorescence. (4) Conclusions: Using the near-infrared fluorescence real-time development technique to assist the biopsy of musculoskeletal tumors may improve the accuracy of core biopsy and help to avoid missed diagnoses, especially for some selected tumors.
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Ideal periosteum materials are required to participate in a sequence of bone repair-related physiological events, including the initial immune response, endogenous stem cell recruitment, angiogenesis, and osteogenesis. However, conventional tissue-engineered periosteal materials have difficulty achieving these functions by simply mimicking the periosteum via structural design or by loading exogenous stem cells, cytokines, or growth factors. Herein, we present a novel biomimetic periosteum preparation strategy to comprehensively enhance the bone regeneration effect using functionalized piezoelectric materials. The resulting biomimetic periosteum possessing an excellent piezoelectric effect and improved physicochemical properties was prepared using a biocompatible and biodegradable poly(3-hydroxybutyric acid-co-3-hydrovaleric acid) (PHBV) polymer matrix, antioxidized polydopamine-modified hydroxyapatite (PHA), and barium titanate (PBT), which were further incorporated into the polymer matrix to fabricate a multifunctional piezoelectric periosteum by a simple one-step spin-coating method. The addition of PHA and PBT dramatically enhanced the physicochemical properties and biological functions of the piezoelectric periosteum, resulting in improved surface hydrophilicity and roughness, enhanced mechanical performance, tunable degradation behavior, and stable and desired endogenous electrical stimulations, which is conducive to accelerating bone regeneration. Benefiting from endogenous piezoelectric stimulation and bioactive components, the as-fabricated biomimetic periosteum demonstrated favorable biocompatibility, osteogenic activity, and immunomodulatory functions in vitro, which not only promoted adhesion, proliferation, and spreading as well as osteogenesis of mesenchymal stem cells (MSCs) but also effectively induced M2 macrophage polarization, thereby suppressing reactive oxygen species (ROS)-induced inflammatory reactions. Through in vivo experiments, the biomimetic periosteum with endogenous piezoelectric stimulation synergistically accelerated the formation of new bone in a rat critical-sized cranial defect model. The whole defect was almost completely covered by new bone at 8 weeks post treatment, with a thickness close to that of the host bone. Collectively, with its favorable immunomodulatory and osteogenic properties, the biomimetic periosteum developed here represents a novel method to rapidly regenerate bone tissue using piezoelectric stimulation.
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Osteogênese , Periósteo , Ratos , Animais , Periósteo/fisiologia , Regeneração Óssea , Engenharia Tecidual , Durapatita/farmacologia , Alicerces Teciduais/químicaRESUMO
Aim: Skeletal involvement of Cryptococcus neoformans is rare and normally associated with disseminated cryptococcosis or potential predisposing factors. Here, we report an atypical case of osteoarticular cryptococcosis in an immunocompetent patient. Case Presentation: We report a case of cryptococcal osteomyelitis in a 45-year-old female who presented with swelling and pain in the left inner thigh. After a biopsy of the pubic bone and surrounding soft tissue, the pathological results and bacterial culture of the biopsy tissue confirmed Cryptococcus neoformans infection. After draining the pus by aspiration and administering oral fluconazole (400 mg/d) treatment, the patient's symptoms disappeared. Conclusion: Cryptococcus neoformans is a rare etiology of infection of the entire pubis, and oral fluconazole and pus aspiration could benefit some cryptococcal osteomyelitis patients with soft-tissue cryptococcal infection.
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Osteogenesis and osteoclastogenesis are closely associated during the bone regeneration process. The development of multifunctional bone repair scaffolds with dual therapeutic actions (pro-osteogenesis and anti-osteoclastogenesis) is still a challenging task for bone tissue engineering applications. Herein, through a facile surface coating process, mussel-inspired polydopamine (PDA) is adhered to the surface of a biocompatible porous scaffold followed by the immobilization of a small-molecule activator (LYN-1604 (LYN)) and the subsequent in situ coprecipitation of hydroxyapatite (HA) nanocrystals. PDA, acting as an intermediate bridge, can provide strong LYN immobilization and biomineralization ability, while LYN targets osteoclast precursor cells to inhibit osteoclastic differentiation and functional activity, which endows LYN/HA-coated hybrid scaffolds with robust anti-osteoclastogenesis ability. Due to the synergistic effects of the LYN and HA components, the obtained three-dimensional hybrid scaffolds exhibited the dual effects of osteoclastic inhibition and osteogenic stimulation, thereby promoting bone tissue repair. Systematic characterization experiments confirmed the successful fabrication of LYN/HA-coated hybrid scaffolds, which exhibited an interconnected porous structure with nanoroughened surface topography, favorable hydrophilicity, and improved mechanical properties, as well as the sustained sequential release of LYN and Ca ions. In vitro experiments demonstrated that LYN/HA-coated hybrid scaffolds possessed satisfactory cytocompatibility, effectively promoting cell adhesion, spreading, proliferation, alkaline phosphatase activity, matrix mineralization, and osteogenesis-related gene and protein secretion, as well as stimulating angiogenic differentiation of endothelial cells. In addition to osteogenesis, the engineered scaffolds also significantly reduced osteoclastogenesis, such as tartrate-resistant acid phosphatase activity, F-actin ring staining, and osteoclastogenesis-related gene and protein secretion. More importantly, in a rat calvarial defect model, the newly developed hybrid scaffolds significantly promoted bone repair and regeneration. Microcomputed tomography, histological, and immunohistochemical analyses all revealed that the LYN/HA-coated hybrid scaffolds possessed not only reliable biosafety but also excellent osteogenesis-inducing and osteoclastogenesis-inhibiting effects, resulting in faster and higher-quality bone tissue regeneration. Taken together, this study offers a powerful and promising strategy to construct multifunctional nanocomposite scaffolds by promoting osteo/angiogenesis and suppressing osteoclastogenesis to accelerate bone regeneration.
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The treatment of osteosarcoma has reached a bottleneck period in recent 30 years, there is an urgent need to find new drugs and treatment methods. Nigericin, an antibiotic derived from Streptomyces hygroscopicus, has exerted promising antitumoral effect in various tumors. The anticancer effect of Nigericin in human osteosarcoma has never been reported. In the present study, we explored the anticancer effects of Nigericin in osteosarcoma in vitro and in vivo. Our results showed that nigericin treatment significantly reduced tumor cell proliferation in dose-dependent and time-dependent in human osteosarcoma cells. Nigericin can inhibit cell growth of osteosarcoma cells, in addition to S-phase cycle arrest, the nigericin induces apoptosis. Furthermore, bioinformatics predicted that Nigericin exerts anticancer effects through inhibiting SRC/STAT3 signaling pathway in osteosarcoma. The direct binding between SRC and activator of transcription 3 (STAT3) was confirmed by Western blot. Nigericin can down regulate STAT3 and Bcl-2. In order to further elucidate the inhibitory effect of nigericin on SRC/STAT3/Bcl-2 signal transduction mechanism, we established human osteosarcoma cancer cells stably expressing STAT3. Western blot confirmed that nigericin exerts anticancer effects on human osteosarcoma cancer cells by directly targeting STAT3. In addition, Nigericin can significantly inhibit tumor migration and invasion. Finally, Nigericin inhibits tumor growth in a mouse osteosarcoma model. The nigericin targeting the SRC/STAT3/BCL-2 signaling pathway may provide new insights into the molecular mechanism of nigericin on cancer cells and suggest its possible clinical application in osteosarcoma.
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Neoplasias Ósseas , Osteossarcoma , Animais , Apoptose , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Camundongos , Nigericina/farmacologia , Nigericina/uso terapêutico , Osteossarcoma/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fator de Transcrição STAT3/metabolismoRESUMO
Deficient bone regeneration causes bone defects or nonunion in a substantial proportion of trauma patients that urges for novel therapies. To develop a reliable therapy, we investigated the effect of negative pressure wound therapy (NPWT) on bone regeneration in vivo in a rat calvarial defect model. Negative pressure (NP) treatment in vitro was mimicked to test its effect on osteoblast differentiation in rat mesenchymal stem cells (MSCs) and MC3T3-E1 cells. Transcriptomic analyses, pharmaceutical interventions, and shRNA knockdowns were conducted to explore the underlying mechanism and their clinical relevance was investigated in samples from patients with nonunion. The potential application of a combined therapy of MSCs in hydrogels with negative pressure was tested in the rat critical-size calvarial defect model. We found that NPWT promoted bone regeneration in vivo and NP treatment induced osteoblast differentiation in vitro. NP induced osteogenesis via activating macroautophagy/autophagy by AMPK-ULK1 signaling that was impaired in clinical samples from patients with nonunion. More importantly, the combined therapy involving MSCs in hydrogels with negative pressure significantly improved bone regeneration in rat critical-size calvarial defect model. Thus, our study identifies a novel AMPK-ULK1-autophagy axis by which negative pressure promotes osteoblast differentiation of MSCs and bone regeneration. NPWT treatment can potentially be adopted for therapy of bone defects.Abbreviations: ADP, adenosine diphosphate; AICAR/Aic, acadesine; ALP, alkaline phosphatase; ALPL, alkaline phosphatase, biomineralization associated; AMP, adenosine monophosphate; AMPK, AMP-activated protein kinase; ARS, alizarin red S staining; ATG7, autophagy related 7; ATP, adenosine triphosphate; BA1, bafilomycin A1; BGLAP/OCN, bone gamma-carboxyglutamate protein; BL, BL-918; BS, bone surface; BS/TV, bone surface per tissue volume; BV/TV, bone volume per tissue volume; C.C, compound C; CCN1, cellular communication network factor 1; COL1A1, collagen type I alpha 1 chain; COL4A3, collagen type IV alpha 3 chain; COL4A4, collagen type IV alpha 4 chain; COL18A1, collagen type XVIII alpha 1 chain; CQ, chloroquine; GelMA, gelatin methacryloyl hydrogel; GO, Gene Ontology; GSEA, gene set enrichment analysis; HIF1A, hypoxia inducible factor 1 subunit alpha; HPLC, high-performance liquid chromatography; ITGAM/CD11B, integrin subunit alpha M; ITGAX/CD11C, integrin subunit alpha X; ITGB1/CdD9, integrin subunit beta 1; KEGG, Kyoto Encyclopedia of Genes and Genomes; MAP1LC3B/LC3B, microtubule associated protein 1 light chain 3 beta; micro-CT, microcomputed tomography; MSCs, mesenchymal stem cells; MTOR, mechanistic target of rapamycin kinase; NP, negative pressure; NPWT, negative pressure wound therapy; PRKAA1/AMPKα1, protein kinase AMP-activated catalytic subunit alpha 1; PRKAA2, protein kinase AMP-activated catalytic subunit alpha 2; PTPRC/CD45, protein tyrosine phosphatase receptor type C; ROS, reactive oxygen species; RUNX2, RUNX family transcription factor 2; SBI, SBI-0206965; SPP1/OPN, secreted phosphoprotein 1; THY1/CD90, Thy-1 cell surface antigen; SQSTM1, sequestosome 1; TGFB3, transforming growth factor beta 3; ULK1/Atg1, unc-51 like autophagy activating kinase 1.
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Autofagia , Tratamento de Ferimentos com Pressão Negativa , Proteínas Quinases Ativadas por AMP/metabolismo , Monofosfato de Adenosina , Fosfatase Alcalina/farmacologia , Animais , Autofagia/fisiologia , Proteína Homóloga à Proteína-1 Relacionada à Autofagia , Regeneração Óssea , Colágeno Tipo IV/farmacologia , Gelatina , Hidrogéis/farmacologia , Integrinas , Metacrilatos , Osteogênese , Ratos , Microtomografia por Raio-XRESUMO
Inspired by natural redwood and bone, a biomimetic strategy is presented to develop a highly bioactive redwood-like nanocomposite via radial freeze casting of biocompatible hydrogels followed by the in situ coprecipitation of a Si-containing CaP hybrid nanocoating (SCPN). The engineered material displays radially aligned macrochannels and a porous network structure similar to those of natural redwood. In addition to acting as a mechanical reinforcement, introducing SCPNs into the weak redwood-like scaffold yields not only a nanoroughened surface topography, a low swelling ratio, retarded enzymatic degradation, and enhanced protein absorption abilities but also the sustained sequential release of Si and Ca ions, thereby providing essential biophysical and biochemical cues for effective bone regeneration. Benefiting from the redwood-like structures and bioactive SCPNs, the biomimetic materials create a favorable microenvironment for promoting the initial adhesion, spreading, proliferation, and migration of bone marrow-derived mesenchymal stem cells and human umbilical vein endothelial cells. Furthermore, the in vitro and in vivo data showed that the biocompatible redwood-like scaffold with precipitated SCPN can synergistically promote osteogenesis and angiogenesis in their aligned direction. Collectively, this work presents a novel bioinspired redwood-like material with multifunctional properties that provides new insight into bone defect repair.
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Osteogênese , Sequoia , Regeneração Óssea , Células Endoteliais da Veia Umbilical Humana , Humanos , Dióxido de Silício , Alicerces TeciduaisRESUMO
OBJECTIVE: This study aims to explore the effect of daidzein, which is a natural isoflavone compound mainly extracted from soybeans, on osteosarcoma and the potential molecular mechanism. MATERIAL AND METHODS: 143B and U2OS osteosarcoma cells were treated with gradient concentrations of daidzein, and MTT assay was used to determine the cell proliferation capacity and IC50. Hoechst 33342 staining and Annexin V-FITC/PI detection were used to determine apoptosis. Cell cycle was analyzed by flow cytometry, and migration ability were detected by transwell assays and scratch wound assay. An osteosarcoma xenograft mice model was applied to investigate the effect of daidzein on osteosarcoma in vivo. Systematic pharmacology and molecular modeling analysis were applied to predict the target of daidzein to osteosarcoma, and the target Src was verified by western blotting. We also observed the effect of daidzein on cell proliferation and apoptosis of Src-overexpressing osteosarcoma cells. RESULTS: In vitro, daidzein significantly inhibited 143B and U2OS osteosarcoma cell proliferation and migration, and induced cell cycle arrest. In vivo, daidzein exerts antitumor effects in osteosarcoma xenograft mice. After systematic screening and analysis, Src-MAPK signaling pathway was predicted as the highest-ranked pathway. Western blot demonstrated that daidzein inhibited phosphorylation of the Src-ERK pathway in osteosarcoma cells. Also, overexpression of Src could partially reverse the inhibitory effects of daidzein on osteosarcoma cell proliferation. CONCLUSION: Daidzein exerts an antitumor effect on osteosarcoma, and the mechanism may be through the Src-ERK pathway.
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INTRODUCTION: Osteosarcoma is a malignant tumor associated with high mortality rates due to the toxic side effects of current therapeutic methods. Tanshinone IIA can inhibit cell proliferation and promote apoptosis in vitro, but the exact mechanism is still unknown. The aims of this study are to explore the antiosteosarcoma effect of tanshinone IIA via Src kinase and demonstrate the mechanism of this effect. MATERIALS AND METHODS: Osteosarcoma MG-63 and U2-OS cell lines were stable transfections with Src-shRNA. Then, the antiosteosarcoma effect of tanshinone IIA was tested in vitro. The protein expression levels of Src, p-Src, p-ERK1/2, and p-AKt were detected by Western blot and RT-PCR. CCK-8 assay and BrdU immunofluorescence assay were used to detect cell proliferation. Transwell assay, cell scratch assay, and flow cytometry were used to detect cell invasion, migration, and cell cycle. Tumor-bearing nude mice with osteosarcoma were constructed. The effect of tanshinone IIA was detected by tumor HE staining, tumor inhibition rate, incidence of lung metastasis, and X-ray. RESULTS: The oncogene role of Src kinase in osteosarcoma is reflected in promoting cell proliferation, invasion, and migration and in inhibiting apoptosis. However, Src has different effects on cell proliferation, apoptosis, and cell cycle regulation among cell lines. At a cellular level, the antiosteosarcoma effect of tanshinone IIA is mediated by Src downstream of the MAPK/ERK and PI3K/AKt signaling pathways. At the animal level, tanshinone IIA played a role in resisting osteosarcoma formation by Src downstream of the MAPK/ERK and PI3K/AKt signaling pathways. CONCLUSION: Tanshinone IIA plays an antiosteosarcoma role in vitro and in vivo and inhibits the progression of osteosarcoma mediated by Src downstream of the MAPK/ERK and PI3K/AKt signaling pathways.
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Osteosarcoma is the most common primary orthopedic malignant bone tumor in adolescents. However, the traditional neoadjuvant chemotherapy regimen has reached the bottleneck. TPZ is a hypoxic prodrug that has a powerful anti-tumor effect in the hypoxic microenvironment of tumors. And ferroptosis is a newly discovered cell death in 2012, and ferroptosis inducers have been used in anti-tumor therapy research in recent decades. Though, the role of TPZ and ferroptosis in osteosarcoma remains unclear. The aim of this study was to investigate the role of TPZ in osteosarcoma and the specific mechanism. MTT assay showed the extraordinary inhibition of TPZ on three osteosarcoma cells under hypoxia. And fluorescence of Fe2+ staining was enhanced by TPZ. Western blotting showed decreased expression of SLC7A11 and GPX4. Lipid peroxidation was confirmed by MDA assay and C11 BODIPY 581/591 staining. SLC7A11 overexpression could restored the proliferation and migration abilities inhibited by TPZ. Thus, we for the first time demonstrated that TPZ could inhibit the proliferation and migration of osteosarcoma cells, and induce ferroptosis in part through inhibiting SLC7A11.
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Sistema y+ de Transporte de Aminoácidos/metabolismo , Antineoplásicos/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Ferroptose/efeitos dos fármacos , Osteossarcoma/tratamento farmacológico , Tirapazamina/farmacologia , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Humanos , Osteossarcoma/metabolismoRESUMO
BACKGROUND Our objective was to explore a synthetic alginate hydrogel delivery system for the delivery of demineralized bone matrix (DBM) particles for bone graft substitutes. MATERIAL AND METHODS The physiochemical properties of surface morphology, porosity measurements, in vitro degradation, equilibrium swelling, and mechanical testing of combined DBM powder and alginate in amounts of 0 mg/1 mL, 25 mg/1 mL, 50 mg/1 mL, and 100 mg/1 mL were detected. In vitro cell culture and in vivo studies using Sprague-Dawley rats were performed to evaluate the biocompatibility and osteoinductivity of DBM-alginate (ADBM) composites. RESULTS DBM particles were uniformly scattered in all composites, and macro-scale pores were omnipresent. All composites showed a similar low degradation rate, with approximately 85% of weight remaining after 15 days. As the concentration of DBM particles in composites increased, degradation in collagenase and elastic modulus increased and the pore area and swelling ratio significantly decreased. No cytotoxicity of ADBM or alginate on mesenchymal stem cells (MSCs) was observed. Cell cultivation with ADBM showed greater osteogenic potential, evidenced by the upregulation of alkaline phosphatase and alizarin red staining activity and the mRNA expression level of marker genes RUNX2, OCN, OPN, and collagen I compared with the cells grown in alginate. Evaluation of ectopic bone formation revealed the osteoinductivity of the ADBM composites was significantly greater than that of DBM particles. Osteoinduction of the composites was demonstrated by a cranial defect model study. CONCLUSIONS The delivery of DBM particles using a synthetic alginate hydrogel carrier may be a promising approach in bone tissue engineering for bone defects.
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Alginatos/química , Matriz Óssea/transplante , Substitutos Ósseos/química , Hidrogéis/química , Engenharia Tecidual/métodos , Animais , Matriz Óssea/química , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: The present study aimed to evaluate the short-term clinical feasibility and efficacy of the minimally invasive endoscopic technique (MIET) for the treatment of symptomatic benign bone lesions. MATERIALS AND METHODS: This single-institution retrospective study investigated 34 patients with symptomatic benign bone lesions from December 2015 to June 2017. Patients involved in this study presented with definite indications for surgical intervention. All procedures were performed under endoscopic guidance for direct visualization followed by complete curettage of tumor tissue. There were 19 males and 15 females, with a mean age of 33.3 ± 12.7 years (range, 17-68 years). The lesions were located in the upper extremities (20, 58.8%), lower extremities (9, 26.5%) and pelvis (5, 14.7%). Primary outcomes were measured before and after intervention using the visual analog scale (VAS), the Musculoskeletal Tumor Society (MSTS) stage and the 36-item Short-Form Health Survey (SF-36) scoring system. RESULTS: Of the 34 patients included in this study, all completed follow-up examinations, with a mean follow-up duration of 22.4 ± 7.6 months (range, 13-35 months). Significantly improved VAS, MSTS and SF-36 scores were observed at 3 months after the initial treatment (P < 0.001), suggesting enhanced pain relief and improved functional recovery and quality of life following surgery. All procedures were technically successful, with the exception of 3 cases (8.8%) manifesting access site numbness; these patients recovered within the follow-up period through symptomatic treatment alone. Only 2 patients (5.9%; one osteoblastoma and one enchondroma) experienced local recurrence and underwent standard open curettage within the follow-up period. All patients showed functional stability without any major complications. CONCLUSION: The MIET is an effective and safe alternative treatment for symptomatic benign bone lesions. The short-term efficacy of MIET was favorable and associated with improved pain palliation, quality of life and functional recovery.
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Infecções por Coronavirus/diagnóstico , Extremidade Inferior , Pneumonia Viral/diagnóstico , Trombose Venosa/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Betacoronavirus/isolamento & purificação , COVID-19 , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Estudos Transversais , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/virologia , SARS-CoV-2 , Índice de Gravidade de Doença , Trombose Venosa/complicações , Trombose Venosa/tratamento farmacológico , Trombose Venosa/epidemiologiaRESUMO
PURPOSE: To evaluate the safety and efficacy of a system aiming to correct scoliosis called "electromagnetically controlled shape-memory alloy rods" (EC-SMAR) used in a rabbit model. METHODS: We heat-treated shape-memory alloy (SMA) rods to achieve a transition temperature between 34 and 47 °C and a C-shape austenite phase. We then developed a water-cooled generator capable of generating an alternating magnetic field (100 kHz) for induction heating. We next studied the efficacy of this system in vitro and determined some parameters prior to proceeding with animal experiments. We then employed a rabbit model, in which we fixed a straight rod along the spinous processes intraoperatively, and conducted induction heating postoperatively every 4 days for 1 month, while performing periodic X-ray assessments. RESULTS: Significant kyphotic deformations with Cobb angles of about 45° (p < 0.01) were created in five rabbits, and no complications occurred throughout the experiment. The rabbits are still very much alive and do not show any signs of discomfort. CONCLUSIONS: This is the first system that can modulate spinal deformation in a gradual, contactless, noninvasive manner through electromagnetic induction heating applied to SMA alloy rods. Although this study dealt with healthy spines, it provides promising evidence that this device also has the capacity to correct human kyphosis and even scoliosis in the future. These slides can be retrieved under Electronic Supplementary Material.
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Escoliose , Ligas de Memória da Forma , Ligas , Animais , Níquel , Coelhos , Escoliose/cirurgia , Coluna Vertebral , TitânioRESUMO
OBJECTIVE: The present study aimed to evaluate the short-term clinical performance and safety of percutaneous microwave ablation (MWA) techniques for the treatment of bone tumors. METHODS: This single-institution retrospective study investigated 47 cases of bone tumors treated by MWA from June 2015 to June 2018. The study included 26 patients (55.3%) with benign bone tumors and 21 patients (44.7%) with malignant bone tumors. The tumors were located in the spine or sacrum (15, 31.9%), the upper extremities (6, 12.8%), the lower extremities (17, 36.2%) and the pelvis (9, 19.1%). Outcomes regarding clinical efficacy, including pain relief, quality of life, and intervention-related complications, were evaluated before and after MWA using the visual analog scale (VAS) and the 36-item Short-Form Health Survey (SF-36) scoring system. RESULTS: Of the 47 patients included in this study, all of them completed follow-up examinations, with a mean follow-up duration of 4.8 ± 1.6 months (range, 2-9 months). Significantly improved VAS and SF-36 scores were recorded after the initial treatment (P<0.001), suggesting that almost 100% of patients experienced pain relief and an improved quality of life following surgery. No major intervention-related complications (e.g., serious neurovascular injury or infection) occurred during or after the treatment. We recorded only three minor posttreatment complications (6.4%, 3/47), which were related to thermal injury that caused myofasciitis and affected wound healing. CONCLUSION: In our study, the short-term efficacy of MWA was considerably favorable, with a relatively low rate of complications. Our results also showed that MWA was effective for pain relief and improved patients' quality of life, making it a feasible treatment alternative for bone tumors.