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1.
Materials (Basel) ; 17(14)2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39063914

RESUMO

The application of organic coatings is the most cost-effective and common method for metallic equipment toward corrosion, whose anti-corrosion property needs to be improved and evaluated in a short time. To rapidly and rationally assess the anti-corrosion property of organic coatings in the ocean splash zone, a new accelerated test was proposed. In the study, the corrosion protection property of the coating samples was measured by an improved AC-DC-AC test in a simulated seawater of 3.5 wt.% NaCl solution, a simulated ocean splash zone test and a new accelerated test combining the above two tests. The results showed that the corrosion rate of the coating samples was high in the improved AC-DC-AC test, which lost its anti-corrosion property after 24 cycles equal to 96 h. The main rapid failure reason was that the time of the water and corrosive media arriving at the carbon steel substrate under the alternating cathodic and anodic polarization with symmetrical positive and negative electric charges was shortened. The entire impedance of the coating samples was improved by about 1.6 times more than that in the initial early time in the simulated ocean splash zone test, which was caused by the damage effect from the salt spraying, drying, humidifying, salt immersion, high temperature and UVA irradiation being weaker than the enhancement effect from the post-curing process by the UVA irradiation. In the new accelerated test, the samples lost their corrosion resistance after 12 cycles equal to 288 h with the fastest failure rate. On account of the coupling process of the salt spraying, drying, humidifying, salt immersion, high temperature combined with the cathodic and anodic polarization and the UVA irradiation, the penetration and transmission rate of water and corrosive media in the coating were further accelerated, the corrosion rate on the carbon steel substrate was reinforced even larger and the destruction of the top polymer molecules was more serious. The new accelerated test showed the strongest damage-acceleration effect than that in the other two tests.

2.
Metab Brain Dis ; 39(5): 895-907, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38771413

RESUMO

Meningioma is a prevalent intracranial malignancy known for its aggressive growth. Circular RNAs (circRNAs) play a crucial role in the development of various cancers. However, their involvement in meningioma remains understudied. This study aimed to investigate the function and underlying mechanism of hsa_circ_0004872 in meningioma. The molecular expression of hsa_circ_0004872, PD-L1 and EIF4A3 was identified by RT-qPCR and/or western blot assays. Cell viability, migration, and invasion were assessed through CCK-8 and Transwell assays, respectively. Cytotoxicity was determined using an LDH assay, and cell apoptosis was monitored by flow cytometry. The RNA and protein interactions were assessed through RNA-protein immunoprecipitation (RIP) and RNA pull down analyses. Our findings revealed that hsa_circ_0004872 expression was significantly downregulated in both meningioma tissue samples and cells. Overexpression of hsa_circ_0004872 inhibited the proliferation, metastasis, and immune escape of meningioma cells, as well as enhanced the cytotoxicity of CD8+ T cells by suppressing PD-L1. Furthermore, hsa_circ_0004872 directly interacted with EIF4A3, leading to the degradation of PD-L1 mRNA. Finally, inhibiting EIF4A3 improved the proliferation, metastasis, and immune escape of meningioma cells, as well as the cytotoxicity of CD8+ T cells. Our study demonstrated that hsa_circ_0004872 mitigated the proliferation, metastasis,and immune escape of meningioma cells by targeting the EIF4A3/PD-L1 axis. These findings suggested that hsa_circ_0004872 and EIF4A3 might serve as promising biological markers and therapeutic targets for meningioma treatment.


Assuntos
Antígeno B7-H1 , Proliferação de Células , Fator de Iniciação 4A em Eucariotos , Neoplasias Meníngeas , Meningioma , RNA Circular , Meningioma/patologia , Meningioma/imunologia , Meningioma/genética , Meningioma/metabolismo , Humanos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , RNA Circular/genética , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/imunologia , Neoplasias Meníngeas/metabolismo , Fator de Iniciação 4A em Eucariotos/genética , Fator de Iniciação 4A em Eucariotos/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Movimento Celular , Evasão Tumoral , Apoptose , RNA Helicases DEAD-box
3.
Acta Biomater ; 180: 308-322, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38615813

RESUMO

Motor functional improvement represents a paramount treatment objective in the post-spinal cord injury (SCI) recovery process. However, neuronal cell death and axonal degeneration following SCI disrupt neural signaling, impeding the motor functional recovery. In this study, we developed a multifunctional decellularized spinal cord-derived extracellular matrix (dSECM), crosslinked with glial cell-derived neurotrophic factor (GDNF), to promote differentiation of stem cells into neural-like cells and facilitate axonogenesis and remyelination. After decellularization, the immunogenic cellular components were effectively removed in dSECM, while the crucial protein components were retained which supports stem cells proliferation and differentiation. Furthermore, sustained release of GDNF from the dSECM facilitated axonogenesis and remyelination by activating the PI3K/Akt and MEK/Erk pathways. Our findings demonstrate that the dSECM-GDNF platform promotes neurogenesis, axonogenesis, and remyelination to enhance neural signaling, thereby yielding promising therapeutic effects for motor functional improvement after SCI. STATEMENT OF SIGNIFICANCE: The dSECM promotes the proliferation and differentiation of MSCs or NSCs by retaining proteins associated with positive regulation of neurogenesis and neuronal differentiation, while eliminating proteins related to negative regulation of neurogenesis. After crosslinking, GDNF can be gradually released from the platform, thereby promoting neural differentiation, axonogenesis, and remyelination to enhance neural signaling through activation of the PI3K/Akt and MEK/Erk pathways. In vivo experiments demonstrated that dSECM-GDNF/MSC@GelMA hydrogel exhibited the ability to facilitate neuronal regeneration at 4 weeks post-surgery, while promoting axonogenesis and remyelination at 8 weeks post-surgery, ultimately leading to enhanced motor functional recovery. This study elucidates the ability of neural regeneration strategy to promote motor functional recovery and provides a promising approach for designing multifunctional tissue for SCI treatment.


Assuntos
Matriz Extracelular , Fator Neurotrófico Derivado de Linhagem de Célula Glial , Neurogênese , Remielinização , Traumatismos da Medula Espinal , Animais , Feminino , Ratos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Matriz Extracelular/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/farmacologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/citologia , Neurogênese/efeitos dos fármacos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Remielinização/efeitos dos fármacos , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/patologia
4.
Food Chem ; 448: 139124, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38554586

RESUMO

In this study, we applied various thermal pretreatment methods (e.g., hot-air, microwave, and stir-frying) to process walnut kernels, and conducted comparative analysis of the physicochemical properties, nutritional components, in vitro antioxidant activity, and flavor substances of the extracted walnut oil (WO). The results indicated that, thermal pretreatment significantly increased the extraction of total trace nutrients (e.g., total phenols, tocopherols, and phytosterols) in WO. The WO produced using microwave had 2316.71 mg/kg of total trace nutrients, closely followed by the stir-frying method, which yielded an 11.22% increase compared to the untreated method. The WO obtained by the microwave method had a higher Oxidative inductance period (4.05 h) and oil yield (2.48%). After analyzing the flavor in WO, we found that aldehydes accounted for 28.77% of the 73 of volatile compounds and 58.12% of the total flavor compound content in microwave-pretreated WO, these percentages were higher than those recorded by using other methods. Based on the comprehensive score obtained by the PCA, microwave-pretreatment might be a promising strategy to improve the quality of WO based on aromatic characteristics.


Assuntos
Aromatizantes , Juglans , Oxirredução , Óleos de Plantas , Paladar , Compostos Orgânicos Voláteis , Juglans/química , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/análise , Aromatizantes/química , Aromatizantes/análise , Óleos de Plantas/química , Antioxidantes/análise , Antioxidantes/química , Temperatura Alta , Micro-Ondas
5.
Exp Hematol ; 133: 104192, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38432427

RESUMO

Hematopoietic stem cell transplantation remains the preferred treatment for a variety of hematopoietic function disorders. To address the issue of limited numbers of hematopoietic stem/progenitor cells (HSPCs), significant progress has been made in the technology for ex vivo expansion of HSPCs. In addition, biomaterial-assisted in vivo production technology for therapeutic cells, including HSPCs, is gradually gaining attention. With the aid of specifically functional biomaterials, researchers can construct bone-like tissues exhibiting typical bone marrow-like structures (termed in vivo osteo-organoids in this article) for the production of therapeutic cells. These in vivo osteo-organoids mimic the native bone marrow niche and provide a microenvironment conducive to the expansion and differentiation of HSPCs. In this perspective article, we systematically summarize the history of in vivo osteo-organoids as a model for studying hematopoiesis and cancer metastasis and propose the challenges faced by the in vivo osteo-organoid production platform for therapeutic cells in terms of clinical translation. Ultimately, we hope to achieve functional customization of in vivo osteo-organoid-derived cells through continuously developed material design methods, so as to meet the treatment needs of different types of diseases and bring hope for life to more people.


Assuntos
Materiais Biocompatíveis , Células-Tronco Hematopoéticas , Humanos , Animais , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Transplante de Células-Tronco Hematopoéticas , Organoides/citologia , Hematopoese , Diferenciação Celular
6.
J Vis Exp ; (204)2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38436379

RESUMO

Hematopoietic stem cell transplantation (HSCT) requires a sufficient number of therapeutic hematopoietic stem/progenitor cells (HSPCs). To identify an adequate source of HSPCs, we developed an in vivo osteo-organoid by implanting scaffolds loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) into an internal muscle pouch near the femur in mice. After 12 weeks of implantation, we retrieved the in vivo osteo-organoids and conducted flow cytometry analysis on HPSCs, revealing a significant presence of HSPC subsets within the in vivo osteo-organoids. We then established a sublethal model of hematopoietic/immune system injury in mice through radiation and performed hematopoietic stem cell transplantation (HSCT) by injecting the extracted osteo-organoid-derived cells into the peripheral blood of radiated mice. The effect of hematopoietic recovery was evaluated through hematological, peripheral blood chimerism, and solid organ chimerism analyses. The results confirmed that in vivo osteo-organoid-derived cells can rapidly and efficiently reconstruct damaged peripheral and solid immune organs in irradiated mice. This approach holds potential as an alternative source of HSPCs for HSCT, offering benefits to a larger number of patients.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Coleta de Tecidos e Órgãos , Humanos , Animais , Camundongos , Organoides , Quimerismo , Células-Tronco Hematopoéticas
7.
Bioact Mater ; 35: 208-227, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38327823

RESUMO

Repair of large bone defects caused by severe trauma, non-union fractures, or tumor resection remains challenging because of limited regenerative ability. Typically, these defects heal through mixed routines, including intramembranous ossification (IMO) and endochondral ossification (ECO), with ECO considered more efficient. Current strategies to promote large bone healing via ECO are unstable and require high-dose growth factors or complex cell therapy that cause side effects and raise expense while providing only limited benefit. Herein, we report a bio-integrated scaffold capable of initiating an early hypoxia microenvironment with controllable release of low-dose recombinant bone morphogenetic protein-2 (rhBMP-2), aiming to induce ECO-dominated repair. Specifically, we apply a mesoporous structure to accelerate iron chelation, this promoting early chondrogenesis via deferoxamine (DFO)-induced hypoxia-inducible factor-1α (HIF-1α). Through the delicate segmentation of click-crosslinked PEGylated Poly (glycerol sebacate) (PEGS) layers, we achieve programmed release of low-dose rhBMP-2, which can facilitate cartilage-to-bone transformation while reducing side effect risks. We demonstrate this system can strengthen the ECO healing and convert mixed or mixed or IMO-guided routes to ECO-dominated approach in large-size models with clinical relevance. Collectively, these findings demonstrate a biomaterial-based strategy for driving ECO-dominated healing, paving a promising pave towards its clinical use in addressing large bone defects.

8.
Small ; 20(3): e2303773, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37702145

RESUMO

Designing suitable nanomaterials is an ideal strategy to enable early diagnosis and effective treatment of diseases. Carbon dots (CDs) are luminescent carbonaceous nanoparticles that have attracted considerable attention. Through facile synthesis, they process properties including tunable light emission, low toxicity, and light energy transformation, leading to diverse applications as optically functional materials in biomedical fields. Recently, their potentials have been further explored, such as enzyme-like activity and ability to promote osteogenic differentiation. Through refined synthesizing strategies carbon dots, a rich treasure trove for new discoveries, stand a chance to guide significant development in biomedical applications. In this review, the authors start with a brief introduction to CDs. By presenting mechanisms and examples, the authors focus on how they can be used in diagnosing and treating diseases, including bioimaging failure of tissues and cells, biosensing various pathogenic factors and biomarkers, tissue defect repair, anti-inflammation, antibacterial and antiviral, and novel oncology treatment. The introduction of the application of integrated diagnosis and treatment follows closely behind. Furthermore, the challenges and future directions of CDs are discussed. The authors hope this review will provide critical perspectives to inspire new discoveries on CDs and prompt their advances in biomedical applications.


Assuntos
Nanopartículas , Pontos Quânticos , Carbono , Medicina de Precisão , Osteogênese
9.
Food Chem ; 438: 138052, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38006698

RESUMO

Walnut oils were obtained by supercritical carbon dioxide extraction (SCB), cold-pressing (CP), hexane extraction (HE), and subcritical butane extraction (SBE), and walnut protein isolates (WPI) from the walnut cakes were performed. The results indicate that SCB has the highest oil yield for walnut oil, which was 62.72%, and the total content of trace nutrients (total tocopherols, total phytosterols, and total phenolic compounds) in SCB-walnut oil was also the highest at 2186.75 mg/kg, approximately 1.05 times higher than CP-walnut oil and 1.21 times higher than SBE-walnut oil. Meanwhile, the treatment of WPI with SCB results in a decrease in ß-Sheet and α-Helix structures and an increase in ß-Turn and Random coil structures. Thereby increasing its oil-holding capacity (OHC) and solubility by approximately 1.16 times and 1.27 times compared to CP, respectively. Interestingly, SCB as a green oil production technology, also has good prospects for retaining WPI functionality characteristics.


Assuntos
Juglans , Juglans/química , Óleos de Plantas/química , Tocoferóis , Antioxidantes/química , Nutrientes
10.
Proc Natl Acad Sci U S A ; 120(46): e2307480120, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37943835

RESUMO

Ischemic diseases lead to considerable morbidity and mortality, yet conventional clinical treatment strategies for therapeutic angiogenesis fall short of being impactful. Despite the potential of biomaterials to deliver pro-angiogenic molecules at the infarct site to induce angiogenesis, their efficacy has been impeded by aberrant vascular activation and off-target circulation. Here, we present a semisynthetic low-molecular sulfated chitosan oligosaccharide (SCOS) that efficiently induces therapeutic arteriogenesis with a spontaneous generation of collateral circulation and blood reperfusion in rodent models of hind limb ischemia and myocardial infarction. SCOS elicits anti-inflammatory macrophages' (Mφs') differentiation into perivascular Mφs, which in turn directs artery formation via a cell-to-cell communication rather than secretory factor regulation. SCOS-mediated arteriogenesis requires a canonical Notch signaling pathway in Mφs via the glycosylation of protein O-glucosyltransferases 2, which results in promoting arterial differentiation and tissue repair in ischemia. Thus, this highly bioactive oligosaccharide can be harnessed to direct efficiently therapeutic arteriogenesis and perfusion for the treatment of ischemic diseases.


Assuntos
Neovascularização Fisiológica , Sulfatos , Camundongos , Animais , Neovascularização Fisiológica/fisiologia , Sulfatos/metabolismo , Camundongos Knockout , Músculo Esquelético/metabolismo , Isquemia/metabolismo , Macrófagos/metabolismo , Membro Posterior/irrigação sanguínea , Modelos Animais de Doenças
11.
Acta Biomater ; 172: 423-440, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37778486

RESUMO

Chemodynamic therapy (CDT) based on generating reactive oxygen species (ROS) is promising for cancer treatment. However, the intrinsic H2O2 is deficient for CDT, and glutathione (GSH) eliminates ROS to protect tumor cells from ROS cytotoxicity. Herein, we propose a strategy to switch the electron flow direction of GSH for O2 reduction and ROS generation rather than ROS clearance by using P(DA-Fc) nanoparticles, which are polymerized from ferrocenecarboxylic acid (Fc) coupled dopamine. P(DA-Fc) NPs with phenol-quinone conversion ability mimic NOX enzyme to deprive electrons from GSH to reduce O2 for H2O2 generation; the following •OH release can be triggered by Fc. Semiquinone radicals in P(DA-Fc) are significantly enhanced after GSH treatment, further demonstrated with strong single-electron reduction ability by calculation. In vitro and in vivo experiments indicate that P(DA-Fc) can consume intrinsic GSH to produce endogenous ROS; ROS generation strongly depends on GSH/pH level and eventually causes tumor cell death. Our work makes the first attempt to reverse the function of GSH from ROS scavenger to ROS producer, explores new roles of PDA-based nanomaterials in CDT beyond photothermal reagents and drug carriers, and provides a new strategy to improve the efficiency of CDT. STATEMENT OF SIGNIFICANCE: P(DA-Fc) nanoparticles performing tumor microenvironment response capacity and tumor reductive power utilize ability were fabricated for CDT tumor suppression. After endocytosis by tumor cells, P(DA-Fc) deprived GSH of electrons for H2O2 and •OH release, mimicking the intrinsic ROS production conducted by NADPH, further inducing tumor cell necrosis and apoptosis. Our work makes the first attempt to reverse the function of GSH from ROS scavenger to producer, explores new functions of PDA-based nanomaterials in CDT beyond photothermal reagents and drug carriers, and provides a new strategy to improve CDT efficiency.


Assuntos
Nanopartículas , Neoplasias , Humanos , Elétrons , Espécies Reativas de Oxigênio , Polifenóis/farmacologia , Peróxido de Hidrogênio , Oxirredução , Portadores de Fármacos , Linhagem Celular Tumoral , Microambiente Tumoral , Glutationa , Neoplasias/tratamento farmacológico
12.
Adv Sci (Weinh) ; 10(33): e2302622, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37847907

RESUMO

Regenerative medicine in tissue engineering often relies on stem cells and specific growth factors at a supraphysiological dose. These approaches are costly and may cause severe side effects. Herein, therapeutic small extracellular vesicles (t-sEVs) endogenously loaded with a cocktail of human vascular endothelial growth factor A (VEGF-A) and human bone morphogenetic protein 2 (BMP-2) mRNAs within a customized injectable PEGylated poly (glycerol sebacate) acrylate (PEGS-A) hydrogel for bone regeneration in rats with challenging femur critical-size defects are introduced. Abundant t-sEVs are produced by a facile cellular nanoelectroporation system based on a commercially available track-etched membrane (TM-nanoEP) to deliver plasmid DNAs to human adipose-derived mesenchymal stem cells (hAdMSCs). Upregulated microRNAs associated with the therapeutic mRNAs are enriched in t-sEVs for enhanced angiogenic-osteogenic regeneration. Localized and controlled release of t-sEVs within the PEGS-A hydrogel leads to the retention of therapeutics in the defect site for highly efficient bone regeneration with minimal low accumulation in other organs.


Assuntos
Osteogênese , Fator A de Crescimento do Endotélio Vascular , Ratos , Humanos , Animais , RNA Mensageiro/genética , Regeneração Óssea/genética , Hidrogéis/farmacologia
13.
Phys Chem Chem Phys ; 25(34): 22862-22869, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37587860

RESUMO

Natural gas hydrates have garnered significant attention as a potential new source of alternative energy, and understanding their formation mechanism is of paramount importance for efficient utilization and pipeline transportation. However, there is no consensus among academics on the formation mechanism of natural gas hydrates. In this paper, we propose a method for promoting the rapid formation of natural gas hydrates based on the rupture of methane nanobubbles, which creates local high temperature and pressure to facilitate the mixing of methane and water. The rapid decrease in system temperature and pressure during the process further enhances the formation of gas hydrates. Using molecular dynamics simulations, we theoretically verify the formation of natural gas hydrates. Our results indicate that the instantaneous rupture of methane nanobubbles induced by shock waves leads to a dramatic increase in the local molecular motion velocity around the bubbles. This results in extreme local high temperature and high pressure, leading to complete mixing of methane and water and rapid formation of gas hydrates during the cooling and pressure drop of the mixture. We confirm our findings by analyzing F3-order parameters, F4-order parameters, and water cage statistics.

14.
Materials (Basel) ; 16(15)2023 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-37570190

RESUMO

This study aimed to improve the absorption rate of laser energy on the surface of nodular cast iron and further improve its thermal stability and wear resistance. After a 0.3 mm thick AlOOH activation film was pre-sprayed onto the polished surface of the nodular cast iron, a GWLASER 6 kw fiber laser cladding system was used to prepare a mixed dense oxide layer mainly composed of Al2O3, Fe3O4, and SiO2 using the optimal laser melting parameters of 470 W (laser power) and 5.5 mm/s (scanning speed). By comparing and characterizing the prefabricated laser-melted surface, the laser-remelted surface with the same parameters, and the substrate surface, it was found that there was little difference in the structure, composition, and performance between the laser-remelted surface and the substrate surface except for the morphology. The morphology, structure, and performance of the laser-melted surface underwent significant changes, with a stable surface line roughness of 0.9 µm and a 300-400 µm deep heat-affected zone. It could undergo two 1100 °C thermal shock cycles; its average microhardness increased by more than one compared to the remelted and substrate surfaces of 300 HV, with a maximum hardness of 900 HV; and the average friction coefficient and wear quantity decreased to 0.4370 and 0.001 g, respectively. The prefabricated activated film layer greatly improved the thermal stability and wear resistance of the nodular cast iron surface while reducing the laser melting power.

15.
J Mater Chem B ; 11(32): 7609-7622, 2023 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-37403708

RESUMO

Hydroxyapatite nanoparticles (HAPNs) have been reported to specifically induce apoptosis and sustained elevation of intracellular Ca2+ concentration ([Ca2+]i) in cancer cells. However, it remains unclear whether calcium overload, the abnormal intracellular accumulation of Ca2+, is the intrinsic cause of cell apoptosis, how HAPNs specifically evoke calcium overload in cancer cells, and which potential pathways were involved in apoptosis initiation in response to calcium overload. In this study, using various cancer and normal cells, we observed a positive correlation between the degree of increased [Ca2+]i and the specific toxicity of HAPNs. Moreover, chelating intracellular Ca2+ with BAPTA-AM inhibited HAPN-induced calcium overload and apoptosis, thus demonstrating that calcium overload was the main cause of HAPN-induced cytotoxicity in cancer cells. Notably, the dissolution of particles outside the cells did not affect cell viability or [Ca2+]i. In contrast, internalized HAPNs dissolved more readily in cancer cells than in normal cells and inhibited the activity of plasma membrane calcium-ATPase solely in cancer cells to prevent extrusion of excessive Ca2+, hence leading to calcium overload in tumor cells. Upon exposure to HAPNs, the Ca2+-sensitive cysteine protease calpain was activated and then cleaved the BH3-only protein Bid. Consequently, cytochrome c was released, and caspase-9 and -3 were activated, leading to mitochondrial apoptosis. However, these effects were alleviated by the calpain inhibitor calpeptin, confirming the involvement of calpain in HANP-induced apoptosis. Therefore, our results demonstrated that calcium overload induced by HAPNs caused cancer cell-specific apoptosis by inhibiting PMCA and activating calpain in tumor cells and thus may contribute to a more comprehensive understanding of biological effects of this nanomaterial and facilitate the development of calcium overload cancer therapy.


Assuntos
Nanopartículas , Neoplasias , Calpaína/metabolismo , Calpaína/farmacologia , Cálcio/metabolismo , Durapatita/farmacologia , Apoptose , Neoplasias/tratamento farmacológico
16.
Adv Healthc Mater ; 12(27): e2301264, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37341519

RESUMO

Macrophages play a crucial role in the complete processes of tissue repair and regeneration, and the activation of M2 polarization is an effective approach to provide a pro-regenerative immune microenvironment. Natural extracellular matrix (ECM) has the capability to modulate macrophage activities via its molecular, physical, and mechanical properties. Inspired by this, an ECM-mimetic hydrogel strategy to modulate macrophages via its dynamic structural characteristics and bioactive cell adhesion sites is proposed. The LZM-SC/SS hydrogel is in situ formed through the amidation reaction between lysozyme (LZM), 4-arm-PEG-SC, and 4-arm-PEG-SS, where LZM provides DGR tripeptide for cell adhesion, 4-arm-PEG-SS provides succinyl ester for dynamic hydrolysis, and 4-arm-PEG-SC balances the stability and dynamics of the network. In vitro and subcutaneous tests indicate the dynamic structural evolution and cell adhesion capacity promotes macrophage movement and M2 polarization synergistically. Comprehensive bioinformatic analysis further confirms the immunomodulatory ability, and reveals a significant correlation between M2 polarization and cell adhesion. A full-thickness wound model is employed to validate the induced M2 polarization, vessel development, and accelerated healing by LZM-SC/SS. This study represents a pioneering exploration of macrophage modulation by biomaterials' structures and components rather than drug or cytokines and provides new strategies to promote tissue repair and regeneration.


Assuntos
Hidrogéis , Cicatrização , Hidrogéis/química , Macrófagos/metabolismo , Materiais Biocompatíveis/química , Matriz Extracelular/química
17.
Adv Sci (Weinh) ; 10(24): e2301592, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37357138

RESUMO

Hematopoietic stem cell transplantation (HSCT) is a well-established method for a variety of acquired and congenital diseases. However, the limited number and sources of therapeutic hematopoietic stem/progenitor cells (HSPCs) hinder the further application of HSCT. A BMP-2 triggered in vivo osteo-organoid that is previously reported, serves as a kind of stem cell biogenerator, for obtaining therapeutic HSPCs via activating the residual regenerative capacity of mammals using bioactive biomaterials. Here, it is demonstrated that targeting the homing signaling of HSPCs elevates the proportions and biological functions of HSPCs in the in vivo osteo-organoid. Notably, it is identified that sulfonated chito-oligosaccharide, a degradation product of sulfonated chitosan, specifically elevates the expression of endothelial protein C receptor on HSPCs and vascular cell adhesion molecule-1 on macrophages in the in vivo osteo-organoid, ultimately leading to the production of adequate therapeutic HSPCs. This in vivo osteo-organoid approach has the potential to provide an alternative HSPCs source for HSCT and benefits more patients.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Sulfatos , Animais , Humanos , Sulfatos/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Transplante de Células-Tronco Hematopoéticas/métodos , Polissacarídeos/metabolismo , Mamíferos
18.
Sci Adv ; 9(1): eadd1541, 2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36608118

RESUMO

Cell therapies and regenerative medicine interventions require an adequate source of therapeutic cells. Here, we demonstrate that constructing in vivo osteo-organoids by implanting bone morphogenetic protein-2-loaded scaffolds into the internal muscle pocket near the femur of mice supports the growth and subsequent harvest of therapeutically useful cells including hematopoietic stem/progenitor cells (HSPCs), mesenchymal stem cells (MSCs), lymphocytes, and myeloid cells. Profiling of the in vivo osteo-organoid maturation process delineated three stages-fibroproliferation, osteochondral differentiation, and marrow generation-each of which entailed obvious changes in the organoid structure and cell type distribution. The MSCs harvested from the osteochondral differentiation stage mitigated carbon tetrachloride (CCl4)-induced chronic liver fibrosis in mice, while HSPCs and immune cells harvested during the marrow generation stage rapidly and effectively reconstituted the impaired peripheral and solid immune organs of irradiated mice. These findings demonstrate the therapeutic potentials of in vivo osteo-organoid-derived cells in cell therapies.


Assuntos
Células-Tronco Hematopoéticas , Fígado , Animais , Camundongos , Diferenciação Celular , Terapia Baseada em Transplante de Células e Tecidos , Organoides
19.
Foods ; 12(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36673332

RESUMO

To overcome the issues in the traditional deacidification processes of peony seed oil (PSO), such as losses of neutral oil and trace nutrients, waste discharge, and high energy consumption, adsorption deacidification was developed. The acid removal capacity of adsorbent-alkali microcrystalline cellulose was evaluated using the isothermal adsorption equilibrium and the pseudo-first-order rate equation. The optimized adsorption deacidification conditions included adsorbent-alkali microcrystalline cellulose at 3%, a heating temperature of 50 °C, and a holding time of 60 min. The physicochemical, bioactive properties, antioxidant capacities, and oxidative stabilities of PSO processed by alkali refining and oil-hexane miscella deacidification were compared under the same operating conditions. Fatty acid content was not significantly different across all three methods. The deacidification rates were 88.29%, 98.11%, and 97.76%, respectively, for adsorption deacidification, alkali refining, and oil-hexane miscella deacidification. Among the three deacidification samples, adsorption deacidification showed the highest retention of tocopherols (92.66%), phytosterols (91.96%), and polyphenols (70.64%). Additionally, the obtained extract preserved about 67.32% of the total antioxidant activity. The oil stability index was increased 1.35 times by adsorption deacidification. Overall, adsorption deacidification can be considered a promising extraction technology in terms of quality as compared to alkali refining and oil-hexane miscella deacidification.

20.
Food Chem ; 404(Pt B): 134683, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36323028

RESUMO

This study investigated the impact of multiple thermal treatments (explosion-puffing, microwave, and roasting) on the processing qualities of sesame seeds and cold-pressed oil. The scanning electron microscopy (SEM) showed fissures and cavities of sesame seed surface upon thermal treatments. The microwave treatment promoted the maximum conversion of sesamolin into sesamol in the sesame oil. Compared with other treatments, explosion-puffing treatment resulted in most significant increases in the multiple beneficial phytochemicals, as well as in vitro antioxidant properties determined by 2,2-dipheny1-1-picrylhydrazyl radical (DPPH) radical scavenging activity, Ferric reducing antioxidant power (FRAP) and oxidative stability index (OSI). Additionally, thermal treatment processing caused varying degrees of damage of crude protein, total amino acids (TAA) and protein structure (tertiary and second structure). In which, explosion-puffing achieved minimal reduction in the first two indicators. Collectively, explosion-puffing might be a preferable thermal treatment method for industrial sesame processing with improved quality specifications.


Assuntos
Sesamum , Sesamum/química , Antioxidantes , Óleo de Gergelim/química , Oxirredução , Sementes
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