RESUMEN
BACKGROUND: Osteosarcoma is the most common malignant tumor in bone and its prognosis has reached a plateau in the past few decades. Recently, metabolic reprogramming has attracted increasing attention in the field of cancer research. In our previous study, P2RX7 has been identified as an oncogene in osteosarcoma. However, whether and how P2RX7 promotes osteosarcoma growth and metastasis through metabolic reprogramming remains unexplored. METHODS: We used CRISPR/Cas9 genome editing technology to establish P2RX7 knockout cell lines. Transcriptomics and metabolomics were performed to explore metabolic reprogramming in osteosarcoma. RT-PCR, western blot and immunofluorescence analyses were used to determine gene expression related to glucose metabolism. Cell cycle and apoptosis were examined by flowcytometry. The capacity of glycolysis and oxidative phosphorylation were assessed by seahorse experiments. PET/CT was carried out to assess glucose uptake in vivo. RESULTS: We demonstrated that P2RX7 significantly promotes glucose metabolism in osteosarcoma via upregulating the expression of genes related to glucose metabolism. Inhibition of glucose metabolism largely abolishes the ability of P2RX7 to promote osteosarcoma progression. Mechanistically, P2RX7 enhances c-Myc stabilization by facilitating nuclear retention and reducing ubiquitination-dependent degradation. Furthermore, P2RX7 promotes osteosarcoma growth and metastasis through metabolic reprogramming in a predominantly c-Myc-dependent manner. CONCLUSIONS: P2RX7 plays a key role in metabolic reprogramming and osteosarcoma progression via increasing c-Myc stability. These findings provide new evidence that P2RX7 might be a potential diagnostic and/or therapeutic target for osteosarcoma. Novel therapeutic strategies targeting metabolic reprogramming appear to hold promise for a breakthrough in the treatment of osteosarcoma.
Asunto(s)
Neoplasias Óseas , Osteosarcoma , Humanos , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Tomografía Computarizada por Tomografía de Emisión de Positrones , Osteosarcoma/genética , Osteosarcoma/patología , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Glucosa , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Receptores Purinérgicos P2X7/genética , Receptores Purinérgicos P2X7/metabolismo , Receptores Purinérgicos P2X7/uso terapéuticoRESUMEN
Single-crystal LiNix Coy Mnz O2 (SC-NCM, x+y+z=1) cathodes are renowned for their high structural stability and reduced accumulation of adverse side products during long-term cycling. While advances have been made using SC-NCM cathode materials, careful studies of cathode degradation mechanisms are scarce. Herein, we employed quasi single-crystalline LiNi0.65 Co0.15 Mn0.20 O2 (SC-NCM65) to test the relationship between cycling performance and material degradation for different charge cutoff potentials. The Li/SC-NCM65 cells showed >77 % capacity retention below 4.6â V vs. Li+ /Li after 400 cycles and revealed a significant decay to 56 % for 4.7â V cutoff. We demonstrate that the SC-NCM65 degradation is due to accumulation of rock-salt (NiO) species at the particle surface rather than intragranular cracking or side reactions with the electrolyte. The NiO-type layer formation is also responsible for the strongly increased impedance and transition-metal dissolution. Notably, the capacity loss is found to have a linear relationship with the thickness of the rock-salt surface layer. Density functional theory and COMSOL Multiphysics modeling analysis further indicate that the charge-transfer kinetics is decisive, as the lower lithium diffusivity of the NiO phase hinders charge transport from the surface to the bulk.
RESUMEN
BACKGROUND: The purpose of this study was to investigate the efficacy of gelatin sponge impregnated with ropivacaine on postoperative pain after transforaminal lumbar interbody fusion (TLIF) in patients with lumbar degenerative diseases. METHODS: We retrospectively reviewed patients who underwent TLIF in our department between August 2018 and January 2020. Patients were divided to ropivacaine group and saline group. A ropivacaine group whom received gelatin sponge impregnated with ropivacaine during operation, and a saline group whom were intraoperatively administered by gelatin sponge impregnated with saline. The two groups were compared in reference to postoperative hospital stay, postoperative complications and visual analog scale (VAS) scores. The consumption of postoperative diclofenac sodium suppository use was also recorded. The Oswestry Disability Index (ODI) scores and Japanese Orthopedic Association (JOA) scores were used for functional evaluation at 1 year postoperatively. RESULT: A total of 127 patients were evaluated in this retrospective study. The mean postoperative hospital stay in the ropivacaine group was significantly lower than saline group. The VAS score was significantly lower in patients receiving gelatin sponge impregnated with ropivacaine as compared with patients in saline group on postoperative day 1, 2, 3 and 4. The number of patients who need the administration of diclofenac sodium suppository and the mean consumption of postoperative diclofenac sodium suppository was significantly lower in the ropivacaine group as compared with saline group. CONCLUSION: The application of gelatin sponge impregnated with ropivacaine around the nerve root in patients undergoing TLIF can effectively control the postoperative pain and reduce postoperative hospital stay.
Asunto(s)
Gelatina , Fusión Vertebral , Humanos , Vértebras Lumbares/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología , Estudios Retrospectivos , Ropivacaína , Fusión Vertebral/efectos adversos , Resultado del TratamientoRESUMEN
Supermagnetic Fe3O4@SiO2 nanoparticles were molecular-imprinted prepared with cellulase as the template. The molecular imprinted nanoparticles were used as support to immobilization of cellulase. The transmission electron microscopy confirmed the core-shell structure and revealed that the size of the nanoparticles was around 10 nm. It was observed that cellulase was immobilized on the nanoparticles successfully from the Fourier transform infrared spectra. The adsorption of cellulase on the nanoparticles was specific and rapid. A high immobilization efficiency of 95% was achieved after the optimization. At 70 degrees C, the half-life of the immobilized cellulase was 3.3-fold of the free enzyme. Compared with the free enzyme, the immobilized cellulase has the same optimal pH, higher optimal temperature, better thermal stability and higher catalytic efficiency. The results strongly suggest that the immobilized cellulase on molecular imprinted Fe3O4@SiO2 has the potential applications in the production of bioethanol, paper and pulp industry, and pharmaceutical industry.
Asunto(s)
Celulasa/metabolismo , Enzimas Inmovilizadas/metabolismo , Nanopartículas de Magnetita/química , Impresión Molecular/métodos , Dióxido de Silicio/química , Estabilidad de Enzimas , Concentración de Iones de Hidrógeno , Cinética , Nanopartículas de Magnetita/ultraestructura , Concentración Osmolar , Espectroscopía Infrarroja por Transformada de Fourier , TemperaturaRESUMEN
Layered Ni-rich oxides are attractive cathode active materials for secondary battery applications. Combining them with inorganic superionic conductors and high-capacity anodes can significantly increase energy density. Herein we successfully synthesized spherical secondary particles of a Mn-substituted LiNiO2, LiNi0.95Mn0.05O2 (a Co-free NMX material), for use in bulk-type lithium-thiophosphate-based all-solid-state batteries.
RESUMEN
Using scanning transmission electron microscopy, along with electron energy loss spectroscopy, under cryogenic conditions, we demonstrate transition-metal dissolution from a layered Ni-rich oxide cathode material and subsequent diffusion into the bulk of a lithium thiophosphate solid electrolyte during electrochemical cycling. This problem has previously only been considered for liquid-electrolyte-based batteries.
RESUMEN
Osteoarthritis (OA) is a common joint disease and is the main cause of physical disability in the elderly. Currently, there is no adequate therapeutic strategy to reverse the progression of OA. Many natural plant extracts have received attention in the treatment of OA due to their potential anti-inflammatory properties, and reduced incidence of adverse events. Dioscin (Dio), a natural steroid saponin, has been demonstrated to inhibit the release of inflammatory cytokines in mouse and rat models of various diseases, and has a protective effect in chronic inflammatory diseases. However, whether Dio alleviates OA progression remains to be explored. In this research, our purposes were to investigate the therapeutic potential of Dio in OA. The results demonstrated that Dio exerted anti-inflammatory effects by repressing NO, PGE2, iNOS and COX-2. Moreover, the application of Dio could repress IL-1ß-induced overexpression of matrix metalloproteinases (MMPs, including MMP1, MMP3, and MMP13) and ADAMTS-5, and improve the synthesis of collagen II and aggrecan, which contribute to the maintenance of chondrocyte matrix homeostasis. The underlying mechanism involved the inhibition of the MAPK and NF-κB signaling pathways by Dio. Furthermore, the treatment of Dio significantly improved the pain behaviors of rat OA models. The in vivo study revealed that Dio could ameliorate cartilage erosion and degradation. These results collectively indicate that Dio can be used as a promising and effective agent for the therapy of OA.
RESUMEN
OBJECTIVE: To investigate whether the radiographic results are affected by cage position in single-level transforaminal lumbar interbody fusion (TLIF). METHOD: Between January 2016 and June 2018, 130 patients (62 males and 68 females, average age: 55.28 ± 10.11 years) who underwent single-level TLIF were analyzed retrospectively. Standing lateral radiographs of the lumbar spine were collected and evaluated preoperatively, postoperatively, and at the time of last follow-up. Cage position in the fused segment was recorded using a central point ratio (CPR), which indicated the cage position. CPR is calculated by dividing the distance between the cage center point and the posterior extent of the superior endplate of the inferior vertebra by the length of the superior endplate of the inferior vertebra. Based on cage positions, the patients were divided into three groups: Anterior Group (n = 38); Middle Group (n = 68); and Posterior Group (n = 24). Segmental lumbar lordosis (SLL), foraminal height (FH), posterior disc height (PDH), and anterior disc height (ADH) were evaluated. A subanalysis was also performed on cage height within each group. RESULTS: The average follow-up time of the patients was 35.20 ± 4.43 months. The mean values of CPR in Anterior Group, Middle Group, and Posterior Group were 0.64, 0.51, and 0.37, respectively. The FH, PDH, and ADH were significantly increased after TLIF in all groups (P < 0.05). There were significant differences in increase of SLL in Anterior Group (4.4°) and Middle Group (3.0°), but not in Posterior Group (0.3°). Furthermore, in the comparison of the three groups, the increase of SLL, FH, and PDH was statistically different (P < 0.05), while not for ADH (P > 0.05). The significant correlations in surgery were: CPR and ΔSLL (r = 0.584, P < 0.001), CPR and ΔFH (r = -0.411, P < 0.001), and CPR and ΔPDH (r = -0.457, P < 0.001). However, ADH had a positive correlation with cage height when the cage was located in anterior and middle of the endplate. Moreover, cage height had a positive correlation with SLL when the cage was located anteriorly and had a negative correlation with SLL when the cage was located posteriorly. FH and PDH both had a positive correlation with cage height in any cage position. CONCLUSION: The cage located in different positions has different effects on radiographic results in single-level TLIF. A thicker cage located anteriorly will gain maximum SLL and avoid the reduction of FH and PDH.
Asunto(s)
Lordosis , Fusión Vertebral , Anciano , Femenino , Humanos , Lordosis/cirugía , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Región Lumbosacra/cirugía , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Estudios Retrospectivos , Fusión Vertebral/métodos , Resultado del TratamientoRESUMEN
Bulk-type solid-state batteries (SSBs) composed of lithium thiophosphate superionic solid electrolytes (SEs) and high-capacity cathode active materials (CAMs) have recently attracted much attention for their potential application in next-generation electrochemical energy storage. However, compatibility issues between the key components in this kind of battery system are difficult to overcome. Here, we report on a protective cathode coating that strongly reduces the prevalence of detrimental side reactions between CAM and SE during battery operation. This is demonstrated using preformed HfO2 nanoparticles as a secondary particle coating for a layered Ni-rich oxide CAM, LiNi0.85Co0.1Mn0.05O2 (NCM85). The preparation of a stable dispersion of the HfO2 nanoparticles enabled the deposition of a uniform coating of thickness ≤11 nm. When incorporated into Li6PS5Cl-based, pellet-stack SSBs, the coated NCM85 showed superior performance in terms of reversibility, cell capacity, longevity, and rate capability over its uncoated counterpart. The effectiveness of the protective coating in mitigating electro-chemo-mechanical degradation was investigated using a suite of physical and electrochemical characterization techniques. In addition, the adaptability to wet processing of the coated NCM85 is demonstrated in slurry-cast SSBs and liquid-electrolyte-based Li-ion cells.
RESUMEN
BACKGROUND: Cartilage damage is a common medical issue in clinical practice. Complete cartilage repair remains a significant challenge owing to the inferior quality of regenerative tissue. Safe and non-invasive magnetic therapy combined with tissue engineering to repair cartilage may be a promising breakthrough. METHODS: In this study, a composite scaffold made of Hydroxyapatite-Collagen type-I (HAC) and PLGA-PEG-PLGA thermogel was produced to match the cartilage and subchondral layers in osteochondral defects, respectively. Bone marrow mesenchymal stem cells (BMSC) encapsulated in the thermogel were stimulated by an electromagnetic field (EMF). Effect of EMF on the proliferation and chondrogenic differentiation potential was evaluated in vitro. 4 mm femoral condyle defect was constructed in rabbits. The scaffolds loaded with BMSCs were implanted into the defects with or without EMF treatment. Effects of the combination treatment of the EMF and composite scaffold on rabbit osteochondral defect was detected in vivo. RESULTS: In vitro experiments showed that EMF could promote proliferation and chondrogenic differentiation of BMSCs partly by activating the PI3K/AKT/mTOR and Wnt1/LRP6/ß-catenin signaling pathway. In vivo results further confirmed that the scaffold with EMF enhances the repair of osteochondral defects in rabbits, and, in particular, cartilage repair. CONCLUSION: Hydrogel-Hydroxyapatite-Monomeric Collagen type-I scaffold with low-frequency EMF treatment has the potential to enhance osteochondral repair.
Asunto(s)
Cartílago Articular , Hidrogeles , Animales , Colágeno Tipo I , Durapatita , Campos Electromagnéticos , Fosfatidilinositol 3-Quinasas , Conejos , Ingeniería de Tejidos/métodos , Andamios del TejidoRESUMEN
BACKGROUND: Intervertebral fusion is the most common surgery to treat lumbar degenerative disease (LDD). And the graft material used in the operation is derived from the iliac crest to promote fusion. However, autografts possess the fatal disadvantage of lack of source. Therefore, economical and practical bone substitutes are urgently needed to be developed. Sinusoidal electromagnetic fields (EMF) combined with tissue engineering techniques may be an appropriate way to promote intervertebral fusion. METHODS: In this research, porous scaffolds made of polycaprolactone (PCL) and nano-hydroxyapatite (nHA) were used as cell carriers. Then, the scaffolds loaded with bone marrow mesenchymal stem cells (BMSCs) were treated with sinusoidal electromagnetic field and the osteogenic capability of BMSCs was tested later. In addition, an intervertebral disc of the tail vertebra of the rat was removed to construct a spinal intervertebral fusion model with a cell-scaffold implanted. The intervertebral fusion was observed and analyzed by X-ray, micro-CT, and histological methods. RESULTS: BMSCs stimulated by EMF possess splendid osteogenic capability under an osteogenic medium (OM) in vitro. And the conditioned medium of BMSCs treated with EMF can further promote osteogenic differentiation of the primitive BMSCs. Mechanistically, EMF regulates BMSCs via BMP/Smad and mitogen-activated protein kinase (MAPK)-associated p38 signaling pathways. In vivo experiments revealed that the scaffold loaded with BMSCs stimulated by EMF accelerated intervertebral fusion successfully. CONCLUSION: In summary, EMF accelerated intervertebral fusion by improving the osteogenic capacity of BMSCs seeded on scaffolds and might boost the paracrine function of BMSCs to promote osteogenic differentiation of the homing BMSCs at the injured site. EMF combined with tissue engineering techniques may become a new clinical treatment for LDD.
Asunto(s)
Células Madre Mesenquimatosas , Osteogénesis , Animales , Células de la Médula Ósea , Diferenciación Celular , Campos Electromagnéticos , Ratas , Ingeniería de Tejidos , Andamios del TejidoRESUMEN
Laminectomy is commonly performed to treat degenerative spinal diseases by reducing compression on the spinal cord and nerve roots. The postoperative epidural fibrosis and epidural adhesions may result in failed back surgery syndrome, which is characterized by the symptoms of lower back pain or leg pain. There is currently no satisfactory treatment for this complication. The pathological processes of epidural fibrosis and epidural adhesions are relevant to the proliferation of fibroblasts, transdifferentiation of fibroblasts into myofibroblasts, and the excessive deposition of extracellular matrix (ECM) protein. According to reports, transforming growth factor-ß1 (TGF-ß1) played a vital role in the development of fibrosis by promoting aforementioned processes. Decorin, an endogenous proteoglycan and natural inhibitor of TGF-ß1, has exhibited prominent anti-fibrosis activity in various scar formation and fibrosis models of many organs. However, the preventive effect of decorin on epidural fibrosis and epidural adhesions requires further investigation. Here, we investigated the therapeutic effects and potential mechanisms of decorin on epidural fibrosis and epidural adhesions. Our results indicated that decorin could significantly suppress the TGF-ß1-induced proliferation, transdifferentiation, and extracellular matrix production in primary fibroblasts. Furthermore, Smad2/3 signaling pathway had been demonstrated to be involved in the preventive effect of decorin. Moreover, administration of decorin in vivo could notably inhibit epidural fibrosis and epidural adhesions after laminectomy. To date, there is no approved therapy to target TGF-ß1 for the treatment of epidural fibrosis and epidural adhesions after laminectomy. Our research proved the anti-fibrosis effect of decorin, which may provide an effective and promising treatment for epidural fibrosis and epidural adhesions.