RESUMEN
BACKGROUND: In current clinical practice, the most commonly used fusion cage materials are titanium (Ti) alloys. However, titanium alloys are non-degradable and may cause stress shielding. ZK60 is a bio-absorbable implant that can effectively avoid long-term complications, such as stress shielding effects, implant displacement, and foreign body reactions. In this study, we aimed at investigating the biomechanical behavior of the cervical spine after implanting different interbody fusion cages. METHODS: The finite element (FE) models of anterior cervical disc removal and bone graft fusion (ACDF) with a ZK60 cage and a Ti cage were constructed, respectively. Simulations were performed to evaluate their properties of flexion, extension, lateral bending, and axial rotation of the cervical spine. Moreover, a side-by-side comparison was conducted on the range of motion (ROM), the deformation of cages, the stress in the cages, bone grafts, and cage-end plate interface. Simultaneously, according to the biomechanical analysis results, the microporous structure of the ZK60 cage was improved by the lattice topology optimization technology and validation using static structure. RESULTS: The ROMs in the current study were comparable with the results reported in the literature. There was no significant difference in the deformation of the two cages under various conditions. Moreover, the maximum stress occurred at the rear of the cage in all cases. The cage's and endplate-cage interface's stress of the ZK60 group was reduced compared with the Ti cage, while the bone graft stress in the ZK60 fusion cage was significantly greater than that in the Ti fusion cage (average 27.70%). We further optimized the cage by filling it with lattice structures, the volume was decreased by 40%, and validation showed more significant biomechanical properties than ZK60 and Ti cages. CONCLUSION: The application of the ZK60 cage can significantly increase the stress stimulation to the bone graft by reducing the stress shielding effect between the two instrumented bodies. We also observed that the stress of the endplate-cage interface decreased as the reduction of the cage's stiffness, indicating that subsidence is less likely to occur in the cage with lower stiffness. Moreover, we successfully designed a porous cage based on the biomechanical load by lattice optimization.
Asunto(s)
Fusión Vertebral , Titanio , Fenómenos Biomecánicos , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/cirugía , Análisis de Elementos Finitos , Humanos , Vértebras Lumbares , Rango del Movimiento Articular , Fusión Vertebral/efectos adversosRESUMEN
Flavonoids are polyphenolic secondary metabolites that function as signaling molecules, allopathic compounds, phytoalexins, detoxifying agents and antimicrobial defensive compounds in plants. Blast caused by the fungus Magnaporthe oryzae is a serious disease affecting rice cultivation. In this study, we revealed that a natural flavonoid, tangeretin, substantially delays the formation of M. oryzae appressoria and blocks the development of blast lesions on rice plants. Our data suggest that tangeretin has antioxidant activity that interferes with conidial cell death/ferroptosis, which is critical for M. oryzae pathogenicity. Tangeretin showed a ferroptosis inhibition efficacy comparable to the well-established liproxstatin-1. Furthermore, overexpression of the NADPH oxidases NOX1 or NOX2 significantly decreased sensitivity toward tangeretin treatment, suggesting Nox-mediated lipid peroxidation as a possible target for tangeretin in regulating redox signaling and ferroptosis in M. oryzae. Our nursery and field tests showed that application of tangeretin can effectively mitigate overall disease symptoms and prevent leaf blast. Our study reveals the plant-derived fungal ferroptosis inhibitor tangeretin as a potential and novel antifungal agrochemical for the sustainable prevention of the devastating blast disease in important cereal crops.
Asunto(s)
Ferroptosis , Magnaporthe , Oryza , Flavonas , Proteínas Fúngicas/metabolismo , Oryza/metabolismo , Enfermedades de las Plantas/microbiologíaRESUMEN
The striking rise of methicillin-resistant Staphylococcus aureus (MRSA) infections has become a serious threat to public health worldwide. In an effort to search for new anti-MRSA agents from natural products, a bioassay-guided phytochemical study was conducted on the semi-mangrove plant Myoporum bontioides A. Gray, which led to the isolation of two new sesquiterpene alkaloids (1 and 2) and six known furanosesquiterpenes (3â»8). Their structures were elucidated on the basis of extensive analysis of their 1D, 2D NMR and mass spectroscopic data. These two new alkaloids (1 and 2) displayed potent anti-MRSA activity with MIC value of 6.25 µg/mL. This is the first report of sesquiterpene alkaloids from the plants of Myoporum genus and their anti-MRSA activity.
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Alcaloides/farmacología , Antibacterianos/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Myoporum/química , Sesquiterpenos/farmacología , Alcaloides/química , Alcaloides/aislamiento & purificación , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Evaluación Preclínica de Medicamentos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Hojas de la Planta/química , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , HumedalesRESUMEN
ARSTRACTN6-methyladenosine (m6A) methylation is the most common and abundant methylation modification of eukaryotic mRNAs, which is involved in tumor initiation and progression. The study aims to explore the potential role and the regulatory mechanism of fat mass and obesity associated (FTO) in osteosarcoma (OS) progression. In this study, we detected the expressions of Krüppel-like factor 3 (KLF3) in OS cells and tissues and found that the mRNA and protein levels of KLF3 were increased in OS cells and tissues and significantly related to tumor size, metastasis, and TNM stage and poor prognosis of OS patients. FTO promoted the proliferation and invasion and suppressed apoptosis of OS cells through cell experiments in vitro. Further mechanism dissection revealed that FTO and YTHDF2 enforced the decay of KLF3 mRNA and decreased its expression. FTO-mediated mRNA demethylation inhibited KLF3 expression in the YTHDF2-dependent manner. Moreover, KLF3 overexpression abrogated FTO-induced oncogenic effects on the proliferation and invasion of OS cells. Overall, our findings showed that FTO-mediated m6A modification of KLF3 promoted OS progression, which may provide a therapeutic target for OS.
Asunto(s)
Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Neoplasias Óseas , Factores de Transcripción de Tipo Kruppel , Osteosarcoma , Adenosina/análogos & derivados , Adenosina/metabolismo , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Neoplasias Óseas/genética , Humanos , Factores de Transcripción de Tipo Kruppel/genética , Osteosarcoma/genética , ARN Mensajero/genéticaRESUMEN
Hydrogen therapy, an emerging therapeutic strategy, has recently attracted much attention in anticancer medicine. Evidence suggests that hydrogen (H2) can selectively reduce intratumoral overexpressed hydroxyl radicals (â¢OH) to break the redox homeostasis and thereby lead to redox stress and cell damage. However, the inability to achieve stable hydrogen storage and efficient hydrogen delivery hinders the development of hydrogen therapy. Furthermore, oxygen (O2) deficiency in the tumor microenvironment (TME) and the electron-hole separation inefficiency in photosensitizers have severely limited the efficacy of photodynamic therapy (PDT). Herein, a smart PdH@MnO2/Ce6@HA (PHMCH) yolk-shell nanoplatform is designed to surmount these challenges. PdH tetrahedrons combine stable hydrogen storage and high photothermal conversion efficiency of palladium (Pd) nanomaterials with near-infrared-controlled hydrogen release. Subsequently, the narrow bandgap semiconductor manganese dioxide (MnO2) and the photosensitizer chlorin e6 (Ce6) are introduced into the PHMCH nanoplatform. Upon irradiation, the staggered energy band edges in heterogeneous materials composed of MnO2 and Ce6 can efficiently facilitate electron-hole separation for increasing singlet oxygen (1O2). Moreover, MnO2 nanoshells generate O2 in TME for ameliorating hypoxia and further improving O2-dependent PDT. Finally, the hyaluronic acid-modified PHMCH nanoplatform shows negligible cytotoxicity and selectively targets CD44-overexpressing melanoma cells. The synergistic antitumor performance of the H2-mediated gas therapy combined with photothermal and enhanced PDT can explore more possibilities for the design of gas-mediated cancer therapy.
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Melanoma , Nanoestructuras , Fotoquimioterapia , Humanos , Compuestos de Manganeso/farmacología , Compuestos de Manganeso/química , Oxígeno , Hidrógeno , Óxidos/farmacología , Óxidos/química , Fototerapia , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Fármacos Fotosensibilizantes/química , Nanoestructuras/química , Melanoma/tratamiento farmacológico , Peróxido de Hidrógeno/química , Microambiente TumoralRESUMEN
Accurate diagnosis and precise and effective treatment are currently the two magic weapons for dealing with cancer. However, a single marker is often associated with multiple cellular events, which is not conducive to accurate diagnosis, and overly mild treatment methods often make the treatment effect unsatisfactory. In this paper, we construct a Au/Pd octopus nanoparticle-DNA nanomachine (Au/Pd ONP-DNA nanomachine) as a fully automatic diagnosis and treatment logic system. In this system, multiple DNA components are targeting detection units, Au/Pd ONPs act as carriers, and Au/Pd ONPs with an 808 nm laser is the treatment unit. In order to achieve the purpose of precise treatment, we will detect two secondary markers under the premise of detecting one major tumor marker. When all of the designated targets are detected (the logic system input is (1, 1, 1), and the output is (1, 1)), the 808 nm laser can be programmed to automatically radiate tumors and perform photothermal therapy and photodynamic therapy. In vivo and in vitro experiments show that this logic system not only can accurately identify tumor cells but also has considerable therapeutic effects.
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Neoplasias , Fotoquimioterapia , Biomarcadores de Tumor , ADN , Humanos , Lógica , Neoplasias/diagnóstico , Neoplasias/terapiaRESUMEN
Multifunctional phototherapy nanoagents for imaging-guided synergistic photothermal therapy (PTT) and photodynamic therapy (PDT) are highly desirable in the field of solid tumor therapy. Nevertheless, the tumor microenvironment (TME) inherently associated with hypoxia significantly hampers the photodynamic effect of these multifunctional nanoagents. Herein, Pd nanocubes coated with an ultrathin Pt shell were prepared and further conjugated with fluorescein labeled and thiol functionalized polyethylene glycol (FITC-PEG-SH) (denoted as Pd@Pt-PEG). The deposition of a Pt shell on Pd nanocubes not only enhances the photothermal performance, exhibiting excellent hyperthermia outcomes and impressive photothermal (PT) imaging quality, but also leads to the formation of singlet oxygen (1O2) induced by plasmonic excitation. In the meantime, the catalytic activity of the Pt layer is enhanced by electronic coupling and the plasmonic effect, which induces the decomposition of endogenous overexpressed hydrogen peroxide (H2O2) in tumors to generate O2 for conquering TME and augmenting 1O2 generation for efficacious tumor cell apoptosis. The modification of FITC-PEG-SH improves the biocompatibility and provides outstanding fluorescence (FL) imaging properties. Upon NIR laser irradiation, Pd@Pt-PEG allows in situ O2 generation and dual-mode imaging-guided synergistic PTT/PDT that effectively kills hypoxic tumor cells, which makes it a promising nanotherapeutic agent for enhanced tumor therapy.
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Hipertermia Inducida , Neoplasias , Fotoquimioterapia , Línea Celular Tumoral , Humanos , Peróxido de Hidrógeno , Hipoxia , Neoplasias/tratamiento farmacológico , Paladio/uso terapéutico , Fármacos Fotosensibilizantes/uso terapéutico , Terapia Fototérmica , Resonancia por Plasmón de Superficie , Microambiente TumoralRESUMEN
Treatment resistance of the tumors to photodynamic therapy (PDT) owing to O2 deficiency largely compromised the therapeutic efficacy, which could be addressed via modulating oxygen levels by using O2 self-enriched nanosystems. Here, we report on augmenting the O2-evolving strategy based on a biomimetic, catalytic nanovehicle (named as N/P@MCC), constructed by the catalase-immobilized hollow mesoporous nanospheres by enveloping a cancer cell membrane (CCM), which acts as an efficient nanocontainer to accommodate nitrogen-doped graphene quantum dots (N-GQDs) and protoporphyrin IX (PpIX). Inheriting the virtues of biomimetic CCM cloaking, the CCM-derived shell conferred N/P@MCC nanovehicles with highly specific self-recognition and homotypic targeting toward cancerous cells, ensuring tumor-specific accumulation and superior circulation durations. N-GQDs, for the first time, have been evidenced as a new dual-functional nanoagents with PTT and PDT capacities, enabling the generation of 1O2 for PDT and inducing local low-temperature hyperthermia for thermally ablating cancer cells and infrared thermal imaging (IRT). Leveraging the intrinsic catalytic features of catalase, such N/P@MCC nanovehicles effectively scavenged the excessive H2O2 to sustainably evolve oxygen for a synchronous O2 self-supply and hypoxia alleviation, with an additional benefit because the resulting O2 bubbles could function as an echo amplifier, leading to the sufficient echogenic reflectivity for ultrasound imaging. Concurrently, the elevated O2 reacted with N-GQDs and PpIX to elicit a maximally increased 1O2 output for augmented PDT. Significantly, the ultrasound imaging coupled with fluorescence imaging, IRT, performs a tumor-modulated trimodal bioimaging effect. Overall, this offers a paradigm to rationally explore O2 self-supply strategies focused on versatile nanotheranostics for hypoxic tumor elimination.
Asunto(s)
Biomimética , Hipoxia de la Célula , Sistemas de Liberación de Medicamentos , Nanopartículas , Neoplasias/tratamiento farmacológico , Oxígeno/metabolismo , Fármacos Fotosensibilizantes/uso terapéutico , Medicina de Precisión , Animales , Línea Celular Tumoral , Humanos , Ratones , Neoplasias/metabolismo , Neoplasias/patología , Fotoquimioterapia , Fármacos Fotosensibilizantes/farmacocinética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Cyclocarya paliurus polysaccharide (CPP) has many beneficial biological activities. Although the antioxidant activity of CPP is well-known, the stress tolerance and underlying mechanism of the activities of CPP have not been determined in vivo. In this study, we applied the emerging model of Caenorhabditis elegans (C. elegans) to observe that CPP imparted stronger resistance to stress than the positive control Astragalus polysaccharide (H2O2- and paraquat-induced oxidative stress, as well as heat stress) without threatening the growth and reproduction of worms. Further studies found that CPP-treated worms had a strong antioxidant defense system that downregulated peroxidation products (ROS, MDA, NEFAs and GSSG) and upregulated antioxidant enzymes and nonenzymatic activities (SOD, CAT, GSH-Px and GSH). The CPP-treated worms also exhibited improved physiological functions, such as inhibition of age pigment and improvement of lifespan, mobility and neuroprotection. Further exploration of the mechanism of action of CPP treatment suggested that increased resistance to CPP might activate stress-inducible genes (sod-3, sod-5, ctl-1, ctl-2, hsp-16.1 and hsp-16.2) via skn-1 and hsf-1, rather than daf-16. These findings suggest that CPP may have health benefits for humans.
Asunto(s)
Proteínas de Caenorhabditis elegans/genética , Proteínas de Unión al ADN/genética , Juglandaceae/química , Extractos Vegetales/farmacología , Factores de Transcripción/genética , Animales , Caenorhabditis elegans/efectos de los fármacos , Caenorhabditis elegans/fisiología , Regulación de la Expresión Génica/efectos de los fármacos , Extractos Vegetales/química , Hojas de la Planta/química , Polisacáridos/química , Polisacáridos/farmacología , Estrés Fisiológico/efectos de los fármacos , Estrés Fisiológico/genéticaRESUMEN
Glycation is a nonenzymatic process in which proteins react with reducing sugar molecules. The identification of glycation sites in protein may provide guidelines to understand the biological function of protein glycation. In this study, we developed a computational method to predict protein glycation sites by using the support vector machine classifier. The experimental results showed that the prediction accuracy was 85.51% and an overall MCC was 0.70. Feature analysis indicated that the composition of k-spaced amino acid pairs feature contributed the most for glycation sites prediction.
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Aminoácidos/genética , Biología Computacional/métodos , Proteínas/genética , Análisis de Secuencia de Proteína/métodos , Glicosilación , Proteínas/química , Proteómica , Máquina de Vectores de SoporteRESUMEN
This study showed that the volatile oils from Myoporum bontioides had a significant repellent action on Plutella xylostella. When Plutella xylostella adults entered into the 4-arm selective olfactometer, the preferred times and average staying duration, in the order from more to less, were 3, 1, 4, and 2 arms, which showed a tendency of keeping away from the treatment arms. The males were more sensitive to the volatile oils than the females, when the velocity of flow was 200 ml.min-1. On the first day of the 3rd bioassay, the oviposition deterrent rate and IIPC of the volatile oils on Plutella xylostella adults was 94.48% and 0.0552, respectively. A liquid component of the volatile oils from Myoporum bontioides was isolated, purified, and identified as myoporone.
Asunto(s)
Mariposas Nocturnas , Myoporum/química , Aceites Volátiles/farmacología , Control Biológico de Vectores , Animales , Femenino , MasculinoRESUMEN
The bioactivity of Myoporum bontioides extracts to Plutella xylostella was studied with IIPC as evaluated index. The results showed that petroleum ether and chloroform extracts had a higher activity than ethyl acetate and alcohol extracts. At 0.01 gDW x ml(-1), the ODR of petroleum ether and chloroform extracts was 84.69% and 79.90%, and 76.47% and 45.70% after treated 1d and 3d, while the IIPC was 0.1565 and 0.2055, respectively. Provided with a higher concentration of 0.05 gDW x ml(-1), the ODR was 88.52% and 72.25%, and 87.33%, 58.37%, while the IIPC was 0.1125 and 0.2620, respectively. From the chloroform extract of Myopdrum Bontioides, three flavonoids, 2, 3-dihydro-5, 7-dihydroxy-2-phenyl-4H-1-Benzopyran-4-one (I), 3, 5, 7-trihydroxy-2-phenyl-4H-1-Benzopyran-4-one (II) and 5, 7-dihydroxy-3-methoxy-2-(4-methoxyphenyl)-4H-1-Benzopyran-4-one (III), were isolated, and their structure were identified based on the analyses of physical and spectrum data. Among these compounds, (II) had a better bioactivity to Plutella xylostella.