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1.
Nanoscale ; 14(28): 10067-10074, 2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35791918

RESUMO

Band structure engineering has a strong beneficial impact on thermoelectric performance, where theoretical methods dominate the investigation of electronic structures. Here, we use angle-resolved photoemission spectroscopy (ARPES) to analyze the electronic structure and report on the thermoelectric transport properties of half-Heusler TiCoSb high-quality single crystals. High degeneracy of the valence bands at the L and Γ band maximum points was observed, which provides a band-convergence scenario for the thermoelectric performance of TiCoSb. Previous efforts have shown how crystallographic defects play an important role in TiCoSb transport properties, while the intrinsic properties remain elusive. Using hard X-ray photoelectron spectroscopy (HAXPES), we discard the presence of interstitial defects that could induce in-gap states near the valence band in our crystals. Contrary to polycrystalline reports, intrinsic TiCoSb exhibits p-type transport, albeit defects still affect the carrier concentration. In two initially identical p-type TiCoSb crystal batches, distinct metallic and semiconductive behaviors were found owing to defects not noticeable by elemental analysis. A varying Seebeck effective mass is consistent with the change at the Fermi level within this band convergence picture. This report tackles the direct investigation of the electronic structure of TiCoSb and reveals new insights and the strong impact of point defects on the optimization of thermoelectric properties.

2.
Regen Biomater ; 9: rbac027, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35592137

RESUMO

Macrophages play a vital role for guiding the fate of osteogenesis- related cells. It is well known that nano-topography and bioactive ions can directly enhance osteogenic behavior. However, the effects of nano-structure combined with bioactive ions release on macrophage polarization and the following osteogenesis and angiogenesis are rarely reported. Herein, Mg(OH)2 films with nano-sheet structures were constructed on the surface of Ti using hydrothermal treatment. The film presented nano-sheet topography and sustained release of Mg ions. The results of in vitro culture of bone marrow-derived macrophages (BMDMs), including PCR, western blot and flow cytometry suggested that the nano-Mg(OH)2 films were more favorable for macrophages polarizing to tissue healing M2 phenotype. Moreover, air-pouch model confirmed that the nano-Mg(OH)2 film coated Ti would induce milder inflammation and thinner fibrous layer in vivo, compared with untreated Ti. Furthermore, macrophages-conditioned culture mediums were collected from nano-Mg(OH)2 coated Ti group was superior for the osteogenic behaviors of mice bone marrow stem cells and the angiogenic behaviors of human umbilical vein endothelial cells. With harmonious early inflammatory response and subsequently improved osteogenesis and angiogenesis, the nano-Mg(OH)2 coated Ti is promising for orthopedic applications.

3.
Langmuir ; 38(18): 5381-5391, 2022 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-35467866

RESUMO

Tumor acidic environment-activated combination therapy holds great promise to significantly decrease side effects, circumvent multiple drug resistance, and improve therapeutic outcomes for cancer treatment. Herein, Sorafenib/ZnPc(PS)4@FeIII-TA nanoparticles (SPFT) are designed with acid-environment turned-on fluorescence to report the activation of triple therapy including photodynamic, chemodynamic, and chemotherapy on hepatocellular carcinoma. The SPFT are composed of SP cores formulated via self-assembly of sorafenib and ZnPc(PS)4, with high drug loading efficiency, and FeIII-TA shells containing FeCl3 and tannic acid. Importantly, the nanoparticles suppress reactive oxygen species (ROS) generation of ZnPc(PS)4 due to their formation in nanoparticles, while assisting simultaneous uptake of the uploaded drugs in cancer cells. The tumor acidic environment initiates FeIII-TA decomposition and accelerates a chemodynamic reaction between FeII and H2O2 to generate toxic •OH. Then, the SP core is decomposed to separate ZnPc(PS)4 and sorafenib, which leads to fluorescence turning-on of ZnPc(PS)4, expedited photodynamic reactions, and burst release of sorafenib. Notably, SPFT shows low dark cytotoxicity to normal cells but exerts high potency on hepatocellular carcinoma cells under near-infrared light irradiation, which is much more potent than either sorafenib or ZnPc(PS)4 alone. This research offers a facile nanomedicine design strategy for cancer therapy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Fotoquimioterapia , Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular Tumoral , Compostos Férricos , Fluorescência , Humanos , Peróxido de Hidrogênio , Neoplasias Hepáticas/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Sorafenibe/farmacologia
4.
Microvasc Res ; 142: 104348, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35245516

RESUMO

BACKGROUND: Retinoblastoma protein (Rb) supports vasoprotective E2F Transcription Factor 1 (E2f1)/Dihydrofolate Reductase (Dhfr) pathway activity in endothelial cells. Cyclin I (Ccni) promotes Cyclin-Dependent Kinase-5 (Cdk5)-mediated Rb phosphorylation. Therefore, we hypothesized that endothelial Ccni may regulate cardiovascular homeostasis, vessel remodeling, and abdominal aortic aneurysm (AAA) formation. METHODS: Aortic CCNI mRNA expression was analyzed in the Gene Expression Omnibus (GEO) GSE57691 cohort consisting of AAA patients (n = 39) and healthy controls (n = 10). We employed wild-type (WT) mice and endothelial Ccni knockout (Ccnifl/flTie2-Cre) mice to conduct in vivo and ex vivo experimentation using an Angiotensin (Ang) II hypertension model and a CaCl2 AAA model. Mice were assessed for Rb/E2f1/Dhfr signaling, biopterin (i.e., biopterin [B], dihydrobiopterin [BH2], and tetrahydrobiopterin [BH4]) production, cardiovascular homeostasis, vessel remodeling, and AAA formation. RESULTS: Aortic CCNI mRNA expression was downregulated in AAA patients. Both Ang II- and CaCl2-induced WT mice showed aortic Ccni upregulation coupled with vasculoprotective upregulation of Rb/E2f1/Dhfr signaling and biopterins. Endothelial Ccni knockout downregulated medial Rb/E2f1/Dhfr signaling and biopterins in Ang II-induced hypertensive mice, which exacerbated eNos uncoupling and H2O2 production. Endothelial Ccni knockout impaired in vivo hemodynamic responses and endothelium-dependent vasodilatation in ex vivo mesenteric arteries in response to Ang II. Endothelial Ccni knockout exacerbated mesenteric artery remodeling and AAA risk in response to Ang II and CaCl2. CONCLUSIONS: Endothelial Ccni acts as a critical negative regulator of eNos uncoupling-mediated ROS generation and thereby reduces vulnerability to hypertension-induced vascular remodeling and AAA development in mice.


Assuntos
Angiotensina II , Aneurisma da Aorta Abdominal , Hipertensão , Remodelação Vascular , Angiotensina II/farmacologia , Animais , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/genética , Aneurisma da Aorta Abdominal/prevenção & controle , Biopterina/metabolismo , Cloreto de Cálcio/metabolismo , Ciclina I/metabolismo , Proteína Rica em Cisteína 61/metabolismo , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Endotélio/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Hipertensão/genética , Hipertensão/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , RNA Mensageiro/metabolismo , Tetra-Hidrofolato Desidrogenase/genética , Tetra-Hidrofolato Desidrogenase/metabolismo
5.
Biomaterials ; 282: 121408, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35189460

RESUMO

The induction of a suitable immune microenvironment by implant is essential for fast bone regeneration. Surface potential is a critical factor that influences immune cells behavior. We apply polydopamine coatings on a titanium (Ti) surface to decrease its surface potential. A lower surface potential favored the expression of adhesion-related genes in bone marrow-derived monocytes (BMDMs) by activating the focal adhesion kinase signaling pathway. A lower negative surface potential results in higher electronic repulsion between the surface and the BMDMs, because the cells exhibit negative charged membrane. To resist the repulsive force, Integrin ß1 and Integrin ß3 in the cell membrane for low surface potential group are upregulated. Furthermore, BMDMs cultured on Ti with low surface potential are more inclined polarize towards anti-inflammatory phenotype (M2) in vitro and in vivo. Whole gene expression analysis reveals that inhibition of the PI3K-Akt-mTOR signaling axis is responsible for the immune regulation ability of Ti with low surface potential. The cytokines secreted by M2 BMDMs promote osteogenic differentiation of a mouse embryo cell line (C3H10T1/2) and increase osteointegration between the implant and newly formed bone. These findings reveal that surface potential regulation is a promising strategy to reprogram the immune microenvironment for bone regeneration and provide insights into developing biomaterials with immunomodulatory functions.


Assuntos
Osteogênese , Fosfatidilinositol 3-Quinases , Animais , Regeneração Óssea , Diferenciação Celular , Camundongos , Propriedades de Superfície , Titânio/farmacologia
6.
Biomaterials ; 283: 121438, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35220020

RESUMO

Bioactive glass nanoparticles (BGN) have attracted increasing attention for their use in bone tissue repair owing to their special osteogenic activity; however, the underlying molecular mechanism remains unclear. In this study, we report a new mechanism by which BGN regulate bone loss in an osteoporosis mouse model. We found that BGN induced the expression of extracellular vesicles secreted by bone marrow mesenchymal stem cells (BGN + BMSC-EVs), which can inhibit osteoclast differentiation in vitro. Furthermore, our results showed that BGN + BMSC-EVs were rich in the long non-coding RNA NRON, which can inhibit the nuclear translocation of NFATc1 by binding to the nuclear factor of activated T cells transcription factors, thereby inhibiting osteoclast differentiation. We validated the function and biological safety of BGN + BMSC-EVs in an ovariectomized mouse model of osteoporosis. The results of in vivo studies showed that BGN + BMSC-EVs could alleviate bone loss in osteoporotic mice, restore the mechanical properties of mouse femurs, and improve the biochemical indicators in the peripheral blood for bone metabolism in mice, with little to no acute, systemic toxicity. This study may provide a new explanation for the role of BGN in inhibiting osteoclast differentiation and relieving bone loss; additionally, the study findings reveal a promising strategy for the treatment of bone resorption disorders.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Nanopartículas , Osteoporose , RNA Longo não Codificante , Animais , Células da Medula Óssea/metabolismo , Diferenciação Celular , Vesículas Extracelulares/metabolismo , Camundongos , Osteoclastos/metabolismo , Osteogênese , Osteoporose/metabolismo , Osteoporose/terapia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
7.
Nat Mater ; 21(2): 203-209, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34811495

RESUMO

A large anomalous Nernst effect (ANE) is crucial for thermoelectric energy conversion applications because the associated unique transverse geometry facilitates module fabrication. Topological ferromagnets with large Berry curvatures show large ANEs; however, they face drawbacks such as strong magnetic disturbances and low mobility due to high magnetization. Herein, we demonstrate that YbMnBi2, a canted antiferromagnet, has a large ANE conductivity of ~10 A m-1 K-1 that surpasses large values observed in other ferromagnets (3-5 A m-1 K-1). The canted spin structure of Mn guarantees a non-zero Berry curvature, but generates only a weak magnetization three orders of magnitude lower than that of general ferromagnets. The heavy Bi with a large spin-orbit coupling enables a large ANE and low thermal conductivity, whereas its highly dispersive px/y orbitals ensure low resistivity. The high anomalous transverse thermoelectric performance and extremely small magnetization make YbMnBi2 an excellent candidate for transverse thermoelectrics.

8.
Regen Biomater ; 8(6): rbab065, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34881047

RESUMO

The distinct structural properties and osteogenic capacity are important aspects to be taken into account when developing guided bone regeneration membranes. Herein, inspired by the structure and function of natural periosteum, we designed and fabricated using electrospinning a fibrous membrane comprising (poly)--ε-caprolactone (PCL), collagen-I (Col) and mineralized Col (MC). The three-layer membranes, having PCL as the outer layer, PCL/Col as the middle layer and PCL/Col/MC in different ratios (5/2.5/2.5 (PCM-1); 3.3/3.3/3.3 (PCM-2); 4/4/4 (PCM-3) (%, w/w/w)) as the inner layer, were produced. The physiochemical properties of the different layers were investigated and a good integration between the layers was observed. The three-layered membranes showed tensile properties in the range of those of natural periosteum. Moreover, the membranes exhibited excellent water absorption capability without changes of the thickness. In vitro experiments showed that the inner layer of the membranes supported attachment, proliferation, ingrowth and osteogenic differentiation of human bone marrow-derived stromal cells. In particular cells cultured on PCM-2 exhibited a significantly higher expression of osteogenesis-related proteins. The three-layered membranes successfully supported new bone formation inside a critical-size cranial defect in rats, with PCM-3 being the most efficient. The membranes developed here are promising candidates for guided bone regeneration applications.

9.
Biomater Sci ; 9(24): 8202-8220, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34727152

RESUMO

The response of immune systems is crucial to the success of biomedical implants in vivo and in particular, orthopedic implants must possess appropriate immunomodulatory functions to allow sufficient osteointegration. In this work, lithium (Li) is incorporated into titanium (Ti) implants by plasma electrolytic oxidation to realize slow and sustained release of Li ions. In vitro cellular behaviors of mice bone marrow derived macrophages (BMDMs), including gene expression, cytokine secretion, and surface marker analysis suggest that a low dose of Li incorporation could enhance the recruitment of BMDMs, restrict pro-inflammatory polarization (M1 phenotype), and promote anti-inflammatory polarization (M2 phenotype). The in vivo air pouch implantation model is constructed to simulate the microenvironment associated with aseptic loosening and the histology results confirm that a small dose of Li could relieve inflammatory reactions surrounding the implants. Moreover, compared to the Li-free group, the macrophage-conditioned culture medium (MCM) from Li-doped samples is more beneficial for the osteogenic differentiation of the mouse embryo cell line (C3H10T1/2) and angiogenesis of human umbilical vein endothelial cells (HUVECs), which is further confirmed by better osteointegration ability in the bone implantation model of Li-incorporating Ti implants. Furthermore, the molecular mechanism study discloses that osteoimmunomodulatory activity of Li-incorporating Ti implants is achieved by regulating the cascade molecules in the PI3K/AKT signalling pathway. This work reveals that favorable immune-modulated osteogenesis and osseointegration of bone implants can be realized by the incorporation of Li which broadens the strategy to develop the next generation of immunomodulatory biomaterials.


Assuntos
Lítio , Osteogênese , Animais , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt
10.
ACS Omega ; 6(38): 24575-24584, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34604639

RESUMO

Mg alloys are promising biodegradable orthopedic implants in the future. However, poor corrosion resistance and biocompatibility limit their wide applications. In this study, a pure Mg-Al layered double hydroxide (Mg-Al LDH) film on AZ31 was prepared through combining hydrofluoric acid pretreatment and hydrothermal treatment. Electrochemical analysis and the immersion test suggested that the as-prepared Mg-Al LDH-coated sample exhibited significantly enhanced corrosion resistance. The in vitro cell culture revealed that the Mg-Al LDH film was favorable for the alkaline phosphatase activity, collagen secretion, and osteogenesis-related gene expression of MC3T3-E1. Furthermore, the LDH-coated sample was beneficial for the migration, vascular endothelial growth factor secretion, and angiogenesis-related gene expression of human umbilical vein endothelial cells. The subcutaneous implantation test demonstrated that the Mg-Al LDH film could protect the substrate from corrosion and induce milder inflammation. The femur implantation demonstrated that the Mg-Al LDH sample showed better bone regeneration and osseointegration than bare AZ31. In summary, the as-prepared pure Mg-Al LDH film is able to enhance the in vitro and in vivo performances of AZ31, indicating a promising application in the orthopedic field.

11.
Nat Commun ; 12(1): 5408, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535648

RESUMO

Valley anisotropy is a favorable electronic structure feature that could be utilized for good thermoelectric performance. Here, taking advantage of the single anisotropic Fermi pocket in p-type Mg3Sb2, a feasible strategy utilizing the valley anisotropy to enhance the thermoelectric power factor is demonstrated by synergistic studies on both single crystals and textured polycrystalline samples. Compared to the heavy-band direction, a higher carrier mobility by a factor of 3 is observed along the light-band direction, while the Seebeck coefficient remains similar. Together with lower lattice thermal conductivity, an increased room-temperature zT by a factor of 3.6 is found. Moreover, the first-principles calculations of 66 isostructural Zintl phase compounds are conducted and 9 of them are screened out displaying a pz-orbital-dominated valence band, similar to Mg3Sb2. In this work, we experimentally demonstrate that valley anisotropy is an effective strategy for the enhancement of thermoelectric performance in materials with anisotropic Fermi pockets.

12.
Regen Biomater ; 8(6): rbab053, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34557310

RESUMO

Primary malignant bone tumors can be life-threatening. Surgical resection of tumor plus chemotherapy is the standard clinical treatment. However, postoperative recovery is hindered due to tumor recurrence caused by residual tumor cells and bone defect caused by resection of tumor tissue. Herein, a multifunctional mussel-inspired film was fabricated on Mg alloy, that is, an inner hydrothermal-treated layer, a middle layer of polydopamine, and an outer layer of doxorubicin. The modified Mg alloy showed excellent photothermal effect and thermal/pH-controlled release of doxorubicin. The synergistic effect of chemotherapy and photothermal therapy enabled the modified Mg alloy to kill bone tumor in vitro and inhibit tumor growth in nude mice. Moreover, because of the controlled release of Mg ions and biocompatibility of polydopamine, the modified Mg alloy supported extracellular matrix mineralization, alkaline phosphatase activity, and bone-related gene expression in C3H10T1/2. Bone implantation model in rats verified that the modified Mg showed excellent osteointegration. These findings prove that the use of mussel-inspired multifunction film on Mg alloy offers a promising strategy for the therapy of primary malignant bone tumor.

13.
Nat Commun ; 12(1): 4576, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34321475

RESUMO

A large non-saturating magnetoresistance has been observed in several nonmagnetic topological Weyl semi-metals with high mobility of charge carriers at the Fermi energy. However, ferromagnetic systems rarely display a large magnetoresistance because of localized electrons in heavy d bands with a low Fermi velocity. Here, we report a large linear non-saturating magnetoresistance and high mobility in ferromagnetic MnBi. MnBi, unlike conventional ferromagnets, exhibits a large linear non-saturating magnetoresistance of 5000% under a pulsed field of 70 T. The electrons and holes' mobilities are both 5000 cm2V-1s-1 at 2 K, which are one of the highest for ferromagnetic materials. These phenomena are due to the spin-polarised Bi 6p band's sharp dispersion with a small effective mass. Our study provides an approach to achieve high mobility in ferromagnetic systems with a high Curie temperature, which is advantageous for topological spintronics.

14.
Adv Healthc Mater ; 10(14): e2100392, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34050712

RESUMO

Pathogenic microorganisms' infections have always been a difficult clinical challenge and lead to serious health problems. Thus, a new strategy is urgently needed. In this study, a simple preparation method for Ti3 C2 MXene colloidal solution is proposed. In vitro, Staphylococcus aureus is treated with 250 µg mL-1 of Ti3 C2 colloidal solution under 5 min of 808 nm near-infrared (NIR) laser irradiation twice. Staphylococcus aureus is eliminated by the "nanothermal blade" effect from Ti3 C2 combined with NIR; the antibacterial rate is 99%, which is higher than the antibacterial rate of pure Ti3 C2 alone 78%. The antibacterial mechanism underlying this treatment may be that the thermal Ti3 C2 nanosheets first transfer heat to the cell membrane, disrupting the membrane structure, disturbing the metabolism and causing leakage of bacterial protein and deoxyribonucleic acid, consequently leading to bacterial death. In vivo results indicate that Ti3 C2 colloidal solution under NIR can effectively kill Staphylococcus aureus and prevent inflammation. Moreover, 250 µg mL-1 Ti3 C2 colloidal solution is nontoxic to mouse organs during the therapeutic process. Therefore, Ti3 C2 colloidal solution can be an ideal candidate for subcutaneous infection application. The antibacterial mechanism proposed in this study aids the investigation of other MXenes as antibacterial agents.


Assuntos
Titânio , Animais , Camundongos
15.
Bioact Mater ; 6(9): 2729-2741, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33665504

RESUMO

Titanium (Ti) has been the most widely used orthopedic implant in the past decades. However, their inert surface often leads to insufficient osteointegration of Ti implant. To solve this issue, two bioactive Mg(OH)2 films were developed on Ti surfaces using hydrothermal treatment (Ti-M1# and Ti-M2#). The Mg(OH)2 films showed nano-flake structures: sheets on Ti-M1# with a thickness of 14.7 ± 0.7 nm and a length of 131.5 ± 2.9 nm, and on Ti-M2# with a thickness of 13.4 ± 2.2 nm and a length of 56.9 ± 5.6 nm. Both films worked as Mg ions releasing platforms. With the gradual degradation of Mg(OH)2 films, weakly alkaline microenvironments will be established surrounding the modified implants. Benefiting from the sustained release of Mg ions, nanostructures, and weakly alkaline microenvironments, the as-prepared nano-Mg(OH)2 coated Ti showed better in vitro and in vivo osteogenesis. Notably, Ti-M2# showed better osteogenesis than Ti-M1#, which can be ascribed to its smaller nanostructure. Moreover, whole genome expression analysis was applied to study the osteogenic mechanism of nano-Mg(OH)2 films. For both coated samples, most of the genes related to ECM-receptor interaction, focal adhesion, and TGF-ß pathways were upregulated, indicating that these signaling pathways were activated, leading to better osteogenesis. Furthermore, cells cultured on Ti-M2# showed markedly upregulated BMP-4 gene expression, suggesting that the nanostructure with Mg ion release ability can better activate BMP-4 related signaling pathways, resulting in better osteogenesis. Nano-Mg(OH)2 films demonstrated a superior osteogenesis and are promising surface modification strategy for orthopedic applications.

16.
Biomater Sci ; 9(9): 3319-3333, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33527931

RESUMO

The bifunctional tissue engineering scaffold with anti-tumor and bone repair properties is promising for the therapy of bone tumor where large bone defects often occur. In this study, hydroxyapatite (HA), poly(dopamine) (PDA), and carboxymethyl chitosan (CMCS) composite scaffolds were prepared by the 3D-printing technology. PDA significantly improved the rheological properties of the slurry for molding, mechanical properties, surface relative potential, and water absorption of composite scaffolds. The osteogenic properties of HA/PDA/CMCS composite scaffolds were evaluated by the cell experiment in vitro. The photothermal properties and anti-tumor effects of the scaffolds in vivo were assessed by the tumor model in nude mice. HA/PDA/CMCS composite scaffolds could promote more osteogenic differentiation of mouse bone marrow stromal cells (mBMSCs) than scaffolds without PDA in vitro and the effect was not hindered by the photothermal process. The PDA-modified composite scaffold had excellent photothermal properties. Cell experiments showed that scaffolds with PDA under irradiation could suppress the tumor effectively. In vivo anti-tumor effects in nude mice indicated that the HA/PDA/CMCS composite scaffold promoted cell apoptosis/necrosis by the direct photothermal effect. Vascular injury was developed subsequently, which lead to the suppression of tumor cell proliferation due to hypoxia-ischemia. HA/PDA/CMCS composite scaffolds with multiple effects have great potential application in bone tumor therapy.


Assuntos
Quitosana , Osteogênese , Animais , Regeneração Óssea , Dopamina , Durapatita , Indóis , Camundongos , Camundongos Nus , Polímeros , Engenharia Tecidual , Tecidos Suporte
17.
Orthop Surg ; 13(1): 185-195, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33442922

RESUMO

OBJECTIVES: To evaluate whether curettage with adjuvant microwave therapy was successful in the treatment of giant cell tumor of the bone (GCTB) in extremities, especially for GCTB with pathological fractures and GCTB of the distal radius. METHODS: This was a retrospective study of 54 cases of GCTB of the extremities treated by curettage with adjuvant microwave therapy between 2007 and 2019. Five patients were lost to follow up and excluded from the study. A total of 33 male and 21 female patients were included in this study. Patients were aged 15-57 years (mean 29.72 ± 10.48 years). Among these patients, there were 10 cases of GCTB with pathological fractures and eight cases of GCTB of the distal radius; one of these cases was combined with a pathological fracture. Comprehensive imaging examinations (X-rays [including lesion site and chest], CT, MRI, emission computed tomography, and pathology examination) of all patients were reviewed. The clinical staging of these patients were evaluated radiologically using the Campanacci classification system based on the extent of spread of the tumor. All patients underwent curettage with adjuvant microwave therapy. Clinical and imaging evaluations were performed in all cases to check for recurrence or metastasis. Lower limb and upper limber function were assessed using the Musculoskeletal Tumor Society score (MSTS), and wrist function was assessed according to the disabilities of the arm, shoulder and hand (DASH) score. Data on surgical-related complications were recorded. RESULTS: All cases were followed up for 24-126 months (mean 60.69 ± 29.61 months). There were 24 patients with a Campanacci grade of 3 and 30 with a Campanacci grade of 2. The 52 patients were continuously disease-free. The local recurrence rate was 3.70% (2 patients). One patient had recurrence in the proximal femur, and the other developed in soft tissue of the calf muscle. No recurrence occurred for GCTB of the distal radius. One recurrence occurred in a GCTB with pathological fractures. The intervals were 9 and 28 months, respectively. The cases of recurrence all had a Campanacci grade of 3 (8.33%). The median MSTS among the 54 patients was 27.67 ± 3.81. The mean wrist function DASH score was 8.30 ± 2.53. The mean MSTS was 28.67 ± 1.63 and 26.71 ± 5.49 for patients with GCTB of the distal radius and for those with pathological fractures, respectively. In comparing patients with and without pathological fractures, there was no significant difference in the MSTS functional score. Five patients had complications after the surgery. CONCLUSION: Curettage with adjuvant microwave ablation therapy provided favorable local control and satisfactory functional outcomes in the treatment of GCTB, especially for cases with pathological fractures and those with GCTB of the distal radius.


Assuntos
Neoplasias Ósseas/terapia , Curetagem/métodos , Extremidades/cirurgia , Tumor de Células Gigantes do Osso/terapia , Micro-Ondas/uso terapêutico , Ablação por Radiofrequência/métodos , Adulto , Terapia Combinada , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
18.
Acta Biomater ; 121: 682-694, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33220487

RESUMO

Osteosarcoma (OS) remains one of the most threatening primary malignant human tumors of the bone, especially in the first or second decade of life. Unfortunately, the clinical therapeutic efficacy has not substantially improved over the past four decades. Therefore, to achieve efficient tumor eradication, a new approach to prevent tumor recurrence is urgently needed. Here, we develop a new bisphosphonate (BP)-loaded microarc oxidation (MAO) coated magnesium-strontium (Mg-Sr) alloy pellet that can inhibit OS, and we illuminate the cellular and molecular mechanisms of the inhibiting effect. To generate such pellets, nitrogen-containing BP is chemically conjugated with a MAO coating on hollow Mg-Sr alloys. We demonstrate that BP coated Mg pellet has multiple desired features for OS therapy through in vitro and in vivo studies. At the cellular level, BP coated Mg pellets not only induce apoptosis and necrosis, as well as antitumor invasion of OS cells in the two-dimensional (2D) cell culture environment, but also damage the formation of multicellular tumor spheroids by OS cell lines in the three-dimensional (3D) cell culture environment. At the in vivo level, BP coated Mg pellets can destroy tumors and prevent neoplasm recurrence via synergistic Mg degradation and drug release. It is further suggested that the superior inhibitory effect on OS of our pellet is achieved by inhibiting the mevalonate pathway at the molecular level. Hence, these results collectively show that the BP coated Mg pellet is a promising candidate for future applications in repairing defects after tumor removal in OS therapy.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Ligas/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Materiais Revestidos Biocompatíveis , Difosfonatos/farmacologia , Humanos , Magnésio/farmacologia , Ácido Mevalônico , Recidiva Local de Neoplasia , Nitrogênio , Osteossarcoma/tratamento farmacológico
19.
J Med Chem ; 63(24): 15655-15667, 2020 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-33300796

RESUMO

Dasatinib is a kinase-targeted drug used in the treatment of leukemia. Regrettably, it remains far from optimal medicine due to insurmountable drug resistance and side effects. Photodynamic therapy (PDT) has proven that it can induce systemic immune responses. However, conventional photosensitizers as immunomodulators produce anticancer immunities, which are inadequate to eliminate residual cancer cells. Herein, a novel compound 4 was synthesized and investigated, which introduces dasatinib and zinc(II) phthalocyanine as the targeting and photodynamic moiety, respectively. Compound 4 exhibits a high affinity to CCRF-CEM cells/tumor tissues, which overexpress lymphocyte-specific protein tyrosine kinase (LCK), and preferential elimination from the body. Meanwhile, compound 4 shows excellent photocytotoxicity and tumor regression. Significantly, compound 4-induced PDT can obviously enhance immune responses, resulting in the production of more immune cells. We believe that the proposed manner is a potential strategy for the treatment of T-cell acute lymphoblastic leukemia.


Assuntos
Fatores Imunológicos/química , Fármacos Fotossensibilizantes/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dasatinibe/química , Dasatinibe/farmacologia , Dasatinibe/uso terapêutico , Feminino , Humanos , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Indóis/química , Indóis/farmacologia , Indóis/uso terapêutico , Isoindóis , Células Matadoras Naturais/citologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Luz , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/genética , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/metabolismo , Camundongos , Camundongos Nus , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Compostos Organometálicos/uso terapêutico , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Espécies Reativas de Oxigênio/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Compostos de Zinco
20.
Mol Med Rep ; 22(2): 906-914, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32468060

RESUMO

Osteosarcoma is the most common malignant bone tumour and the second leading cause of cancer­related death in children and adolescents. Microwave ablation has an excellent therapeutic effect on bone tumours by instantaneously increasing the temperature in the tumour; however, there is a risk of damaging the surrounding healthy tissues by exposure to a high temperature when the treatment power is too large. In the present study, two anti­tumour reagents, a heat shock protein 90 (HSP90) inhibitor (PF­04929113) and a transforming growth factor­ß1 (TGF­ß1) inhibitor (SB­525334) were employed to enhance the therapeutic effect of mild­power microwave ablation. It was revealed that microwaving to 48˚C combined with HSP90 and TGF­ß1 inhibitors significantly increased the apoptotic rate of VX2 cells. The same results were observed during in vivo experiments using New Zealand rabbits to model osteosarcoma. In addition, the results indicated that the expression of cytochrome c, caspase­3 and caspase­9 were upregulated in response to the treatment, which indicated that the mitochondrial apoptotic signalling pathway had been activated. These findings may provide a novel strategy for the development of microwave ablation in osteosarcoma treatment, which could effectively kill tumour cells without damaging the surrounding normal tissues.


Assuntos
Neoplasias Ósseas/terapia , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Micro-Ondas/uso terapêutico , Osteossarcoma/terapia , Ablação por Radiofrequência/métodos , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Benzamidas/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Modelos Animais de Doenças , Glicina/uso terapêutico , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Imidazóis/uso terapêutico , Indazóis/uso terapêutico , Quinoxalinas/uso terapêutico , Coelhos , Fator de Crescimento Transformador beta1/metabolismo , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/efeitos da radiação
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