RESUMEN
OBJECTIVE: To investigate the expression of miR-182 in patients with fracture of tibial plateau (FTP) and its effects on osteoblasts and fracture healing. PATIENTS AND METHODS: The patients with fracture of tibial plateau treated in our hospital and healthy subjects who received physical examination from January 2017 to January 2018 were collected. The expression of miR-182 in the serum was detected. The osteoblasts from SD rats were cultured and transfected with miR-182, anti-miR-182, miR-NC or anti-miR-NC using transfection reagent LipofectamineTM 2000. The proliferation, alkaline phosphatase (ALP) activity, calcification and osteogenic gene expression of osteoblasts were detected. The rat models with fracture of tibial plateau were divided into control group, fracture group, fracture+miR-182 group, and fracture+anti-miR-182 group. The levels of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and transforming growth factor ß (TGFß) in serum were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the controls, the expression of miR-182 in serum was significantly elevated in patients with fracture of tibial plateau. Overexpression of miR-182 inhibited the proliferation of osteoblasts, while the knockdown of miR-182 increased the proliferation. MiR-182 could decrease the ALP activity of osteoblasts, while anti-miR-182 increased the ALP activity. Osteoblast calcification ability was significantly decreased by overexpression of miR-182. Knockdown of miR-182 increased the calcification ability of osteoblasts and the expression of osteogenic genes. MiR-182 could inhibit the expression of osteogenic genes. The levels of VEGF, EGF and TGFß in the fracture group were higher than those in the control group, while the levels in the fracture+miR-182 group were higher than those in the fracture group. The levels of VEGF, EGF and TGFß in the anti-miR-182 group were lower than those in the fracture group. CONCLUSIONS: MiR-182 is elevated in patients with fracture of tibial plateau, which can inhibit the proliferation and differentiation of osteoblasts and affect the fracture healing. The knockdown of miR-182 might be a new method for treating fracture healing.
Asunto(s)
Curación de Fractura/genética , MicroARNs/genética , Fracturas de la Tibia/genética , Anciano , Anciano de 80 o más Años , Animales , Diferenciación Celular , Células Cultivadas , Femenino , Humanos , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Osteoblastos/metabolismo , Ratas , Ratas Sprague-Dawley , Fracturas de la Tibia/metabolismoRESUMEN
Objective: To evaluate the efficacy and safety of mycophenolate mofetil (MMF) in neuromyelitis optica spectrum disorder (NMOSD). Method: From September 2014 to February 2017, NMOSD patients with seropositive aquaporin4-IgG was enrolled through a multicenter, prospective study, and the annual recurrence rate (ARR), Expanded Disability Status Scale (EDSS) and MMF-related side effects before and after MMF treatment were compared. Results: Ninety patients were enrolled in the study. After being treated for a median of 12 months (1-30 months), the median ARR decreased from 1.1 pre-MMF to 0 post-MMF (P<0.001), and the median EDSS score decreased from 4.0 pre-MMF to 3.0 post-MMF (P<0.001). The EDSS score reduced significantly after 90 days' treatment (P<0.05). The main adverse events included the deranged liver enzymes (19%, 17/90), respiratory infection (11%, 10/90), urinary tract infection (6%, 5/90), varicella-zoster infection (6%, 5/90), anemia (6%, 5/90), leucopenia (6%, 5/90), diarrhea (2%, 2/90), hair loss (1%, 1/90); 11% (10/90) patients experienced severe adverse events, and 6% (5/90) patients discontinued MMF. Conclusions: MMF could significantly reduce the ARR and EDSS score of NMOSD. However, awareness on side effects should be raised.
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Neuromielitis Óptica , Humanos , Inmunosupresores , Ácido Micofenólico , Estudios Prospectivos , Autocontrol , Resultado del TratamientoRESUMEN
Adenanthin, a natural diterpenoid isolated from the leaves of Isodon adenanthus, has recently been reported to induce leukemic cell differentiation by targeting peroxiredoxins (Prx) I and II. On the other hand, increasing lines of evidence propose that these Prx proteins would become potential targets to screen drugs for the prevention and treatment of solid tumors. Therefore, it is of significance to explore the potential activities of adenanthin on solid tumor cells. Here, we demonstrate that Prx I protein is essential for the survival of hepatocellular carcinoma (HCC) cells, and adenanthin can kill these malignant liver cells in vitro and xenografts. We also show that the cell death-inducing activity of adenanthin on HCC cells is mediated by the increased reactive oxygen species (ROS) levels. Furthermore, the silencing of Prx I or Prx II significantly enhances the cytotoxic activity of adenanthin on HCC, whereas the ectopic expression of Prx I and Prx II but not their mutants of adenanthin-bound cysteines can rescue adenanthin-induced cytotoxicity in Prxs-silenced HCC cells. Taken together, our results propose that adenanthin targets Prx I/II to kill HCC cells and its therapeutic significance warrants to be further explored in HCC patients.
Asunto(s)
Antineoplásicos Fitogénicos/toxicidad , Apoptosis/efectos de los fármacos , Diterpenos de Tipo Kaurano/toxicidad , Peroxirredoxinas/metabolismo , Animales , Antineoplásicos Fitogénicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Diterpenos de Tipo Kaurano/uso terapéutico , Células Hep G2 , Humanos , Isodon/química , Isodon/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Estrés Oxidativo/efectos de los fármacos , Peroxirredoxinas/antagonistas & inhibidores , Peroxirredoxinas/genética , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Trasplante HeterólogoRESUMEN
This experiment aimed to investigate the effects of blockade of cerebral lymphatic drainage on cerebral ischemic damage. Seventy six Wistar rats were divided randomly into middle cerebral artery occlusion (MCAO) group and MCAO plus cerebral lymphatic blockade (MCAO+CLB) group for the experiment. The contents of water and electrolytes, the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in the ischemic brain tissue were detected at 24, 48 and 72 hours after the operation. The morphologic examination was also performed. In MCAO group, contents of water, sodium and calcium in the ischemic brain tissue increased significantly at any time after the operation. The SOD activity decreased while the MDA content increased markedly. The morphologic findings showed severe damage of ischemic brain tissue and neurons. In MCAO+CLB group, the above parameters were altered more obviously. The present observation suggests that blockade of cerebral lymphatic drainage may deteriorate ischemic brain damage after MCAO.