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Pre-eclampsia (PE) is a major cause of hypertension in maternal and fetal. Atlastin-1 (ATL1), one regulator of endoplasmic reticulum (ER) morphology, participates in tubular ER formation and protein synthesis. The objective of this study is to investigate the role and molecular mechanism of ATL1 in PE. GEO databases showed that ATL1 was upregulated in PE patients. Our data also found that ATL1 was highly expressed in PE placental tissues. The cell viability, proliferation, migration, and invasion of HTR-8/SVneo cells increased/decreased after the downregulation/upregulation of ATL1. The mTOR pathway is the downstream pathway of ATL1. The levels of p-p70S6K and p-mTOR were increased/decreased after the downregulation/upregulation of ATL1. Moreover, rapamycin, an inhibitor of mTOR pathway, reversed the promotive effect of siATL1 on proliferation, migration, and invasion in HTR-8/SVneo cells. In conclusion, ATL1 inhibits the proliferation and invasion of trophoblast cells via the inhibition of the mTOR signaling pathway in HTR-8/SVneo cells.
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Placenta , Trofoblastos , Humanos , Femenino , Embarazo , Trofoblastos/metabolismo , Placenta/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Proliferación Celular/fisiología , Movimiento CelularRESUMEN
BACKGROUND: Previous studies have reported that resveratrol has various biological effects such as anti-inflammatory, antioxidant, and antitumor. This study aimed to investigate the effects of resveratrol on blood glucose and blood lipids in rats with gestational diabetes mellitus (GDM). METHODS: The rat diabetes model was prepared by one-time intraperitoneal injection of streptozotocin (STZ, 35 mg/kg). Fasting blood glucose was measured by using a blood glucose meter. The ELISA method was used to detect the levels of insulin, leptin, adiponectin, resistin, TNF-α, and IL-6. The content of TC, TG, LDL-C, and HDL-C was determined by using an automatic biochemical detector. RESULTS: Compared with the GDM group, the insulin level in the resveratrol (120 and 240 mg/kg) treatment group was significantly increased. But, the blood glucose level and body weight were significantly reduced. The content of TC, TG, and LDL-C in the resveratrol (240 mg/kg) treatment group was significantly reduced, and the content of HDL-C was significantly increased. In addition, leptin, resistin, TNF-α, and IL-6 levels in the 240 mg/kg resveratrol treatment group were significantly reduced, and adiponectin was significantly increased. Also, resveratrol (240 mg/kg) was stronger than metformin hydrochloride in improving insulin secretion and regulating blood lipids and adipokine content. CONCLUSION: Resveratrol has a dose-dependent effect on GDM rats to increase insulin secretion, reduce blood glucose and body weight, and regulate blood lipids and plasma adipokines.
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OBJECTIVE: To investigate the safety profiles of Motherwort injection (MI). METHODS: A multi-center, prospective and drug- derived hospital intensive monitoring method was conducted to assess the safety of MI in real world applications. This study was based on a very large population after the injection was approved and marketed in China. All patients using the injection in participating hospitals were monitored to determine the incidence, pattern, severity and outcome of associated adverse events. RESULTS: The post-marketing surveillance was performed in 10 094 female patients from April to December, 2015. The incidence of adverse drug reactions (ADRs) was 0.79¡ë(8/10 094). Among the 8 patients, the reported adverse events mainly included systemic abnormalities, such as fever, chills and eyelid edema; skin and appendages disorders, such as pruritus and rash; gastrointestinal disorders, such as nausea, abdominal distension and pain; heart rate and rhythm disorders, such as palpitation and increased heart rate. All of these ADRs were mild in severity. CONCLUSION: In this study the ADRs incidence rate of MI is very low, which supports that it is generally safe for use in obstetric and gynecological diseases. However, the total number of 8 ADRs recorded over a relatively short time span seems limited, and the low number of reports could not represent an absolute guarantee of safety.
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Long noncoding RNA PVT1 has been reported to be dysregulated and play vital roles in a variety of cancers. However, the functions and molecular mechanisms of PVT1 in cervical cancer remain unclear. The objective of this study was to investigate the expression, clinical significance, biological roles, and underlying functional mechanisms of PVT1 in cervical cancer. Our results revealed that PVT1 is upregulated in cervical cancer tissues. Enhanced expression of PVT1 is associated with larger tumor size, advanced International Federation of Gynecology and Obstetrics stage, and poor prognosis of cervical cancer patients. Using gain-of-function and loss-of-function approaches, we demonstrated that overexpression of PVT1 promotes cervical cancer cells proliferation, cell cycle progression and migration, and depletion of PVT1 inhibits cervical cancer cell proliferation, cell cycle progression, and migration. Mechanistically, we verified that PVT1 binds to EZH2, recruits EZH2 to the miR-200b promoter, increases histone H3K27 trimethylation level on the miR-200b promoter, and inhibits miR-200b expression. Furthermore, the effects of PVT1 on cervical cell proliferation and migration depend upon silencing of miR-200b. Taken together, our findings confirmed that PVT1 functions as an oncogene in cervical cancer and indicated that PVT1 is not only an important prognostic marker, but also a potential therapy target for cervical cancer.
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Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Epigénesis Genética , Regulación de la Expresión Génica , Silenciador del Gen , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Neoplasias del Cuello Uterino/fisiopatología , Adulto , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Perfilación de la Expresión Génica , Histonas/metabolismo , Humanos , Metilación , Persona de Mediana Edad , Unión Proteica , Procesamiento Proteico-Postraduccional , Neoplasias del Cuello Uterino/patologíaRESUMEN
OBJECTIVE: To observe the anti-tumor effect of matrine combined with cisplatin on U14 rat models of cervical cancer. METHODS: A total of 80 female Kunming rats were used to establish U14 rat models of cervical cancer and then divided into groups I, II, III, IV, with 20 rats in each. For Group I, the control group, injection of normal saline was given around the tumors. For Group II, injection of 2 mg/kg cisplatin was given around the tumors. For Group III, injection of 75 mg/kg matrine was given around the tumors while the combined injection of matrine and cisplatin was given for Group IV with the same doses as Groups II and III. The animals were sacrificed 10 d after the injection and tumors were taken out for the comparisons of tumor weights after injection and calculation of anti-tumor rates, while thymus and spleen were taken for thymus index and spleen index. Blood in eyeball was collected for determination of changes in serum creatinine and urea nitrogen levels. Sections of tumor issue were prepared and morphological changes in tumor tissue cells were observed by using immunohistochemistry technique. RESULTS: After injection, the thymus index and spleen index in Groups III and IV were significantly higher than those in Groups I and II (P < 0.05) while the two indexes in Group II were significantly lower than Group I (P < 0.05). The tumor weights in Groups II and IV were significantly smaller than those in Groups I and III (P < 0.05) with significantly higher anti-tumor rates than Groups I and III (P < 0.05). The serum creatinine and urea nitrogen levels in Groups III and IV were significantly lower than Group II (P < 0.05) and the two indicators in Group III were significantly lower than those in Group IV (P < 0.05). The observation under the histological microscope showed densely arranged tumor cells in Group I, growing as a crumby structure and diffuse appearance, with hyperchromatic and large nuclei, and abundant cytoplasm. In the case of Group II, it showed less tumor cells, with extensive degenerative necrosis, sparse arrangement and karyopyknosis as well as karyoclasis. For Group III, necrosis of tumor cells in different sizes and heterogeneous color in nuclei were observed. For Group IV, the number of tumor cells was significantly smaller than Groups I and III and the tumor cells presented an appearance of crumby structure as cancer nests, with more proliferation of connective tissue. CONCLUSIONS: The treatment of matrine combined with cisplatin can significantly improve the anti-tumor effect on U14 rats with cervical cancer, which can be a new option for the treatment for cervical cancer.
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Exploring multi-functional properties in a single material is the focus for future material design and applications. In this work, we investigated the multiferroic property of Cu doped ZnO films using a combination of X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray absorption spectroscopy (XAS), classical magnetometry and electric measurements. The results show that the texture of Cu doped ZnO films is deteriorated with an increase in Cu contents, whereas the dielectric property is improved due to the introduction of Cu ions. The XAS result reveals that the Cu atoms occupy the substitutional Zn sites in the ZnO host, and thus induce local electric dipoles owing to the displacement of the Cu-O bond. The presence of oxygen vacancies together with Cu ions facilitates the movement of the ferroelectric domain boundary, and contributes to the ferromagnetism due to the indirect exchange between Cu atoms and large-sized vacancy orbitals. The Cu doped ZnO film is a feasible promising candidate for applications in multiferroic devices.