RESUMO
This study explores the regulatory effect of astragaloside â £ on miR-17-5 p and its downstream proprotein convertase subtillisin/kexin type 9(PCSK9)/very low density lipoprotein receptor(VLDLR) signal pathway, aiming at elucidating the mechanism of astragaloside â £ against atherosclerosis(AS). In cell experiment, oxidized low-density lipoprotein(ox-LDL) was used for endothelial cell injury modeling with vascular smooth muscle cells(VSMCs). Then cells were classified into the model group, miR-17-5 p inhibitor group, blank serum group, and astragaloside â £-containing serum group based on the invention. Afterward, cell viability and the expression of miR-17-5 p, VLDLR, and PCSK9 mRNA and protein in cells in each group were detected. In animal experiment, 15 C57 BL/6 mice were used as the control group, and 45 ApoE~(-/-) mice were classified into the model group, miR-17-5 p inhibitor group, and astragaloside â £ group, with 15 mice in each group. After 8 weeks of intervention, the peripheral serum levels of interleukin-6(IL-6), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α), and the expression of miR-17-5 p, VLDLR, and PCSK9 mRNA in the aorta of mice were detected. The pathological changes of mice in each group were observed. According to the cell experiment, VSMC viability in the miR-17-5 p inhibitor group and the astragaloside â £-containing serum group was higher than that in the model group(P<0.05). The mRNA and protein expression of miR-17-5 p and VLDLR in VSMCs in the miR-17-5 p inhibitor group and the astragaloside â £-containing serum group was lower than that in the model group(P<0.05), but the mRNA and protein expression of PCSK9 was higher than that in the model group(P<0.05). As for the animal experiment, the levels of IL-6 and TNF-α in the peripheral serum of the miR-17-5 p inhibitor group and the astragaloside â £ group were lower(P<0.05) and the serum level of IL-10 was higher(P<0.05) than that of the model group. The mRNA expression of miR-17-5 p and VLDLR in the aorta in the miR-17-5 p inhibitor group and the astragaloside â £ group was lower(P<0.05), and PCSK9 mRNA expression was higher(P<0.05) than that in the model group. Pathological observation showed mild AS in the miR-17-5 p inhibitor group and the astragaloside â £ group. In summary, astragaloside â £ can prevent the occurrence and development of AS. The mechanism is that it performs targeted regulation of miR-17-5 p, further affecting the PCSK9/VLDLR signal pathway, inhibiting vascular inflammation, and thus alleviating endothelial cell injury.
Assuntos
Aterosclerose , MicroRNAs , Animais , Aterosclerose/tratamento farmacológico , Aterosclerose/genética , Lipoproteínas LDL/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Pró-Proteína Convertase 9/genética , Pró-Proteína Convertase 9/metabolismo , Receptores de LDL/genética , Receptores de LDL/metabolismo , Saponinas , Transdução de Sinais , TriterpenosRESUMO
OBJECTIVE: To observe the therapeutic effect of "Tiaoyi Sanjiao" ï¼regulating and tonifying the triple energizerï¼acupuncture and moxibustion in the treatment of cancer-related fatigue of advanced non-small cell lung cancer and observe its influence on lymphocyte count. METHODS: The cancer-related fatigue patients with advanced non-small cell lung cancer who met the inclusive criteria were randomly divided into 2 groups, with 77 cases in each group. Patients in the control group were treated with conventional Chinese and Western medicine. In the treatment group, on the base of the treatment as the control group, "Tiaoyi Sanjiao" acupuncture and moxibustion was appliedï¼mild moxibustion at Danzhong ï¼»CV17ï¼½, Zhongwanï¼»CV12ï¼½, Qihaiï¼»CV6ï¼½, bilateral Zusanliï¼»ST36ï¼½, and acupuncture at bilateral Xuehaiï¼»SP10ï¼½, Waiguanï¼»SJ5ï¼½, Taichongï¼»LR3ï¼½ï¼. KPS score, Piper scale, percentage and absolute count of lymphocyte subsets of the two groups before and after treatment were observed. RESULTS: Compared with pre-treatment, the KPS scores of both groups were significantly increased after treatment (P<0.05); the behavioral dimension score of the Piper scale, and the percentage of B cells of the control group decreased significantly(P<0.05); the behavioral dimension, emotional dimension, sensory dimension scores, and total score of the Piper scale in the treatment group were significantly reduced(P<0.05), while the percentage of CD3+T cells and absolute counts of CD3+T cells, CD4+T cells and CD8+T cells of the treatment group were significantly increased (P<0.05). After treatment, in comparison with the control group, behavioral dimension score of the Piper scale in the treatment group decreased significantly(P<0.05); the percentage and absolute counts of B cells and CD4+T cells, the absolute count of CD3+T cells in the treatment group were up-regulated (P<0.05). CONCLUSION: "Tiaoyi Sanjiao" acupuncture and moxibustion can significantly alleviate the fatigue state and improve the quality of life in patients with advanced non-small cell lung cancer, which may be achieved by regulating the number of lymphocytes and improving immune function.
Assuntos
Terapia por Acupuntura , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Moxibustão , Pontos de Acupuntura , Carcinoma Pulmonar de Células não Pequenas/terapia , Fadiga/etiologia , Fadiga/terapia , Humanos , Neoplasias Pulmonares/terapia , Qualidade de VidaRESUMO
OBJECTIVE: To observe the impacts of moxibustion at Zusanli (ST 36) on the improvements in the quality of life in the patients with advanced malignant tumor. METHODS: A total of 60 patients with advanced malignant tumor were randomized into an observation group and a control group, 30 cases in each one. In the control group, the routine symptomatic scheme was adopted. In the observation group, on the base of the routine treatment, moxibustion was applied to bilateral Zusanli (ST 36), once a day. The observation period was 12 days. The percentages of , and in T lymphocyte subset, the ratio of / , the value of hemoglobin, Karnofsky score (KPS) and the main symptom score of traditional Chinese medicine (TCM) were compared before and after treatment in the two groups. RESULTS: In comparison before and after treatment in the two groups as well as between the two groups, the differences were not significant in the contents of , and , hemoglobin and the ratio of / (all P>0.05). In the observation group, KPS after treatment was increased as compared with the score before treatment (P<0.05). In the observation group, the scores of the main TCM symptoms, i.e. lassitude, insomnia, poor appetite, spontaneous sweating, dizziness and vertigo as well as the total score after treatment were all reduced as compared with the scores before treatment (all P<0.01). In the control group, the difference was not significant in the score of each item (all P>0.05). In the observation group, the improvements in lassitude, short breath, poor appetite, dizziness and vertigo, complexion, palpitation, soreness and weakness of the lumber region and knee joint as well as the total score were better than the control group (P<0.05, P<0.01). CONCLUSION: Moxibustion at Zusanli (ST 36) effectively regulates the immune balance and relieves the clinical symptoms in the patients with advanced malignant tumor.
Assuntos
Terapia por Acupuntura , Moxibustão , Neoplasias , Humanos , Neoplasias/terapia , Qualidade de VidaRESUMO
Hypertensive disorders of pregnancy are closely related to maternal mortality and morbidity. Calcium supplementation during pregnancy seems to reduce the risk of hypertensive disorders. No systematic review on multicentre RCTs of calcium supplementation during pregnancy has been published. The purpose of this study was to report a quantitative systematic review of the effectiveness of calcium supplementation during pregnancy on reducing the risk of hypertensive disorders of pregnancy and related problems. Publications over the years of 1991-2012 were searched through PubMed, Science Direct, EMBASE, CINAHL and Web of Science. The literatures were selected of the multicentre RCTs on calcium supplementation during pregnancy in prevention of hypertensive disorders and related problems. Reference lists from the studies were also examined for additional references. Studies were critically appraised by three independent reviewers, and the Cochrane Handbook was used to assess the quality of those included trials. Four studies were included in this systematic review. All included studies were high quality, with low risk of bias. There was an observed risk reduction in hypertension in calcium group. However, there was no reduction in the risk of severe gestational hypertension, pre-eclampsia, severe pre-eclampsia, preterm birth and low birthweight. Calcium supplementation appears to reduce the risk of hypertension in pregnancy.
Assuntos
Cálcio da Dieta/uso terapêutico , Suplementos Nutricionais , Hipertensão Induzida pela Gravidez/prevenção & controle , Feminino , Humanos , Estudos Multicêntricos como Assunto , Gravidez , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Structure-activity relationship for the inhibition of Schisandra chinensis's ingredients toward (Uridine-Diphosphate) UDP-glucuronosyltransferases (UGTs) activity was performed in the present study. In vitro incubation system was employed to screen the inhibition capability of S. chinensis's ingredients, and in silico molecular docking method was carried out to explain possible mechanisms. At 100 µM of compounds, the activity of UGTs was inhibited by less than 90% by schisandrol A, schisandrol B, schisandrin, schisandrin C, schisantherin A, gomisin D, and gomisin G. Schisandrin A exerted strong inhibition toward UGT1A1 and UGT1A3, with the residual activity to be 7.9% and 0% of control activity. Schisanhenol exhibited strong inhibition toward UGT2B7, with the residual activity to be 7.9% of control activity. Gomisin J of 100 µM inhibited 91.8% and 93.1% of activity of UGT1A1 and UGT1A9, respectively. Molecular docking prediction indicated different hydrogen bonds interaction resulted in the different inhibition potential induced by subtle structure alteration among schisandrin A, schisandrin, and schisandrin C toward UGT1A1 and UGT1A3: schisandrin A > schisandrin > schisandrin C. The detailed inhibition kinetic evaluation showed the strong inhibition of gomisin J toward UGT1A9 with the inhibition kinetic parameter (Ki ) to be 0.7 µM. Based on the concentrations of gomisin J in the plasma of the rats given with S. chinensis, high herb-drug interaction existed between S. chinensis and drugs mainly undergoing UGT1A9-mediated metabolism. In conclusion, in silico-in vitro method was used to give the inhibition information and possible inhibition mechanism for S. chinensis's components toward UGTs, which guide the clinical application of S. chinensis.
Assuntos
Glucuronosiltransferase/antagonistas & inibidores , Extratos Vegetais/farmacologia , Schisandra , Animais , Ciclo-Octanos , Dioxóis , Medicamentos de Ervas Chinesas/farmacologia , Interações Ervas-Drogas , Lignanas , Compostos Policíclicos , Ratos , Schisandra/química , Relação Estrutura-AtividadeRESUMO
AIMS: To investigate the regulating effects of catalpol on the hypothalamic-pituitary- adrenocortical-axis (HPA) in an Alzheimer's disease (AD) rat model. METHODS: Healthy male Wistar Rats were selected. The AD model was generated by orthotopic injection of beta-amyloid 25-35 (Abeta25-35) into the right lateral ventricle. The animals were divided into five study groups: Catalpol at low dose (5 mg/kg), Catalpol at high dose (10 mg/kg), model control group and sham surgery control group, n = 9 respectively. The serum concentration of hydrocortisone (HYD), adrenocorticotropin (ACTH) and corticotropin releasing hormone (CRH) determined by Enzyme-Linked Immunosorbent Assay (ELISA). Structural alterations of the hypothalamus were examined by H&E stain and electron microscope. The CRH receptor 1 (CRHR1) positive neurons were detected with immunohistochemistry. RESULTS: Serum HYD level was significantly increased (p < 0.01), and both ACTH and CRH were dramatically decreased (p < 0.01) in the AD model group rats compared with normal control rats at day 7. Catalpol treatment was able to improve the hormone secretion disorder in AD model group rats compared with the model group (p < 0.01 or p < 0.05) in particular at 21 days. Structure damage of hypothalamus in the AD rat as evidenced less CRHR1 positive neurons, rough endoplasmic reticulum dilation and degranulation, and mitochondrial swelling under electron microscope. Catalpol treatment at both high and low doses was able to alleviate the structure damage of the hypothalamus in the AD rats. CONCLUSIONS: Catalpol could improve the endocrine function of the HPA and alleviate the structural damage of hypothalamus in AD rats.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Glucosídeos Iridoides/farmacologia , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Doença de Alzheimer/fisiopatologia , Animais , Hormônio Liberador da Corticotropina/sangue , Ensaio de Imunoadsorção Enzimática , Hipocampo/patologia , Sistema Hipotálamo-Hipofisário/patologia , Hipotálamo/patologia , Imuno-Histoquímica , Microscopia Eletrônica de Transmissão , Neurônios/metabolismo , Sistema Hipófise-Suprarrenal/patologia , Ratos , Receptores de Hormônio Liberador da Corticotropina/biossínteseRESUMO
OBJECTIVE: To investigate the difference of macroscopic characteristics between cultivated Gentiana macrophylla and wild one, analyze the correlation among its main quality traits and preliminary screen cultivated Gentiana macrophylla from different habitats based on quality traits. METHODS: Measured and obtained characteristic index, including main root length, lateral root number, taproot diameter, residue stem number and dry weight, and analyzed data by SPSS 12.0 statistical software. RESULTS: The main characteristics of cultivated Gentiana macrophylla were all better than those of the wild one. The characteristics was sequenced as follows: lateral root number > dry weight > main root lengthy > taproot diameter > residue stem number in order of difference. There were remarkable positive correlations among main quality traits. The optimal germplasm was located in Yulinpu of Liufengguan Village, Nanxing Town, Feng County in Shaanxi Province. CONCLUSION: Cultivated Gentiana macrophylla is relatively robust, having more branching roots with light colour of surface and section compared with the wild one. The paper provides suggestions for the revising of macroscopic characteristics of Gentiana macrophylla in the next edition of pharmacopoeia; The data offer scientific reference for screening excellent germplasm, introduction expansion and reasonable utilization of resources as well.
Assuntos
Gentiana/anatomia & histologia , Raízes de Plantas/anatomia & histologia , Plantas Medicinais/anatomia & histologia , Análise por Conglomerados , Gentiana/crescimento & desenvolvimento , Raízes de Plantas/crescimento & desenvolvimento , Plantas Medicinais/crescimento & desenvolvimento , Controle de QualidadeRESUMO
BACKGROUND: Three-dimensional conformal radiation therapy (3DCRT)/intensity-modulated radiation therapy (IMRT) combined with or without transcatheter arterial chemoembolization (TACE) for locally advanced hepatocellular carcinoma (HCC) has shown favorable outcomes in local control and survival of locally advanced HCC. However, intra-hepatic spreading and metastasis are still the predominant treatment failure patterns. Sorafenib is a multikinase inhibitor with effects against tumor proliferation and angiogenesis. Maintenance Sorafenib would probably prevent or delay the intrahepatic and extrahepatic spread of HCC after radiotherapy, which provides the rationale for the combination of these treatment modalities. METHODS AND DESIGN: Patients with solitary lesion (bigger than 5 cm in diameter) histologically or cytologically confirmed HCC receive TACE (1-3 cycles) plus 3DCRT/IMRT 4-6 weeks later. Maintenance Sorafenib will be administered only for the patients with non-progression disease 4 to 6 weeks after the completion of radiotherapy. The dose will be 400 mg, p.o., twice a day. Sorafenib will be continuously given for 12 months unless intolerable toxicities and/or tumor progression. If no more than 3 patients discontinue Sorafenib treatment who experience dose-limiting toxicity after necessary dose modification and delay and/or radiation-induced liver disease in the first 15 enrolled patients, the study will recruit second fifteen patients for further evaluating safety and efficacy of treatment. Hypothesis of the current study is that Sorafenib as a maintenance therapy after combined therapy of 3DCRT/IMRT and TACE is safe and superior to radiotherapy combined with TACE alone in terms of time to progression (TTP), progression-free survival (PFS) and overall survival (OS) in comparison to historical data. DISCUSSION: A recent meta-analysis showed TACE in combination with radiotherapy, improved the survival and the tumor response of patients, and was thus more therapeutically beneficial. In this study, local therapy for HCC is the combination of TACE and radiotherapy. Radiation exposure as a kind of stress might induce the compensatory activations of multiple intracellular signaling pathway mediators, such as PI3K, MAPK, JNK and NF-kB. Vascular endothelial growth factor (VEGF) was identified as one factor that was increased in a time- and dose-dependent manner after sublethal irradiation of HCC cells in vitro, translating to enhanced intratumor angiogenesis in vivo. Therefore, Sorafenib-mediated blockade of the Raf/MAPK and VEGFR pathways might enhance the efficacy of radiation, when Sorafenib is followed sequentially as a maintenance modality. (ClinicalTrials.gov number, NCT00999843.).