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BACKGROUND: Recent studies in cancer biology suggest that metabolic glucose reprogramming is a potential target for cancer treatment. However, little is known about drug intervention in the glucose metabolism of cancer stem cells (CSCs) and its related underlying mechanisms. METHODS: The crude realgar powder was Nano-grinded to meets the requirements of Nano-pharmaceutical preparations, and Nano-realgar solution (NRS) was prepared for subsequent experiments. Isolation and characterization of lung cancer stem cells (LCSCs) was performed by magnetic cell sorting (MACS) and immunocytochemistry, respectively. Cell viability and intracellular glucose concentration were detected by MTT assay and glucose oxidase (GOD) kit. Protein expressions related to metabolic reprogramming was detected by ELISA assay. Determination of the expression of HIF-1α and PI3K/Akt/mTOR pathways was carried out by RT-PCR and western blotting analysis. A subcutaneous tumor model in BALB/c-nu mice was successfully established to evaluate the effects of Nano-realgar on tumor growth and histological structure, and the expression of HIF-1α in tumor tissues was measured by immunofluorescence. RESULTS: Nano-realgar inhibits cell viability and induces glucose metabolism in LCSCs, and inhibits protein expression related to metabolic reprogramming in a time- and dose-dependent manner. Nano-realgar downregulated the expression of HIF-1α and PI3K/Akt/mTOR pathways in vitro and in vivo. Nano-realgar inhibits tumor growth and changes the histological structure of tumors through in vivo experiments and consequently inhibits the constitutive activation of HIF-1α signaling. CONCLUSIONS: These results reveal that Nano-realgar inhibits tumor growth in vitro and in vivo by repressing metabolic reprogramming. This inhibitory effect potentially related to the downregulation HIF-1α expression via PI3K/Akt/mTOR pathway.
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Antineoplásicos/administración & dosificación , Arsenicales/administración & dosificación , Glucosa/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Células Madre Neoplásicas/metabolismo , Sulfuros/administración & dosificación , Células A549 , Antígeno AC133/metabolismo , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Arsenicales/química , Arsenicales/farmacología , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Pulmonares/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Nanopartículas , Células Madre Neoplásicas/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Sulfuros/química , Sulfuros/farmacología , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Basically, Mg-Al layered double hydroxide (LDH) coatings are prepared on the surface of micro-arc oxidation (MAO) coated magnesium (Mg) alloys at a high temperature or a low pH value. This scenario leads to the growth rate of LDH coating inferior to the dissolution rate of the MAO coating. This in turn results in limited corrosion resistance of the composite coating. In this study, a Mg-Al LDH coating on MAO-coated Mg alloy AZ31 is prepared through a water bath with a higher pH (13.76) at a lower temperature (60 °C). FE-SEM, EDS, XRD, XPS, and FT-IR are applied to analyze the surface morphology, chemical compositions, and growth process. Electrochemical polarization, electrochemical impedance spectroscopy (EIS) and hydrogen evolution tests are employed to evaluate the corrosion resistance of the samples. The results disclose that the MAO coating is completely covered by the nanosheet-structured LDH coating with a thickness of approximately 3.8 µm. The corrosion current density of the MAO-LDH composite coating is decreased four orders of magnitude in comparison to its substrate; the presence of a wide passivation region in anodic polarization branch demonstrates its strong self-healing ability, indicating the hybrid coating possesses excellent corrosion resistance. The formation mechanism of the LDH coating on the MAO-coated Mg alloy is proposed. Furthermore, the cytocompatibility is assessed via an indirect extraction test for MC3T3-E1 pre-osteoblasts, which indicates an acceptable cytocompatibility of osteoblasts for the composite coating.
RESUMEN
Micro-arc oxidation (MAO) coating with outstanding adhesion strength to Mg alloys has attracted more and more attention. However, owing to the porous structure, aggressive ions easily invaded the MAO/substrate interface through the through pores, limiting long-term corrosion resistance. Therefore, a dense and biocompatible tantalum oxide (Ta2O5) nanofilm was deposited on MAO coated Mg alloy AZ31 through atomic layer deposition (ALD) technique to seal the micropores and regulate the degradation rate. Surface micrography, chemical compositions and crystallographic structure were characterized using FE-SEM, EDS, XPS and XRD. The corrosion resistance of all samples was evaluated through electrochemical and hydrogen evolution tests. Results revealed that the Ta2O5 film mainly existed in the form of amorphousness. Moreover, uniform deposition of Ta2O5 film and effective sealing of micropores and microcracks in MAO coating were achieved. The current density (i corr) of the composite coating decreased three orders of magnitude than that of the substrate and MAO coating, improving corrosion resistance. Besides, the formation and corrosion resistance mechanisms of the composite coating were proposed.
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<p><b>OBJECTIVE</b>To explore the operative technique and clinical results of using peroneal perforator-based sural neurofasciocutaneous flaps to repair skin and soft tissue defects in lower extremities.</p><p><b>METHODS</b>From January 2009 to March 2012, 26 patients with skin and soft tissue defects at distal region of leg and foot were hospitalized. Among them, 9 patients suffered from tendon or bone exposure at the distal region of leg after injury due to traffic accident; 4 patients suffered from skin defects in the ankle as a result of electric injury; 8 patients suffered from chronic ulcer at the distal part of leg and foot; 5 patients suffered from plantar pressure ulcer. After debridement, soft tissue defect sizes ranged from 11 cm×5 cm to 18 cm×13 cm. According to the position and size of the defects, peroneal perforator-based sural neurofasciocutaneous flaps were designed and procured to repair the skin and soft tissue defects. The size of flaps ranged from 12 cm×6 cm to 20 cm×15 cm. Flap donor sites were closed by direct suture or skin grafting.</p><p><b>RESULTS</b>Twenty-five flaps survived completely. Only one flap suffered partial margin necrosis in the size of 2 cm×1 cm, which was healed after dressing change. Patients were followed up for 6 to 12 months. The appearance and sensation of flaps were satisfactory; no ulcer occurred; the movement of lower extremities was normal.</p><p><b>CONCLUSIONS</b>It is suitable to repair the skin and soft tissue defects at distal region of leg and foot with the peroneal perforator-based sural neurofasciocutaneous flap, as it possesses reliable blood supply, long and non-bulky pedicle, and sufficient available size. The operation is also easy to perform.</p>
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Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Extremidad Inferior , Cirugía General , Procedimientos de Cirugía Plástica , Métodos , Traumatismos de los Tejidos Blandos , Cirugía General , Nervio Sural , Trasplante , Colgajos QuirúrgicosRESUMEN
<p><b>OBJECTIVE</b>To investigate the clinical application of superior or inferior gluteal artery perforator flaps for the gluteal sores.</p><p><b>METHODS</b>Before operation, the perforator artery was detected by Doppler flowmeter and labeled. The perforator flap was designed, including the perforator artery, but not the gluteal maximum muscle.</p><p><b>RESULTS</b>From Aug. 2006 to May 2009, 15 cases were treated. The flap size ranged from 6 cm x 8 cm to 7 cm x 15 cm. All the flaps survived completely without hematoma, seroma or other complication.</p><p><b>CONCLUSIONS</b>The gluteal maximum muscle-reserved gluteal artery perforator flap is a good choice for gluteal sore with reliable blood supply and less morbidity in donor site.</p>