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1.
Aging (Albany NY) ; 16(4): 3386-3403, 2024 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-38345573

RESUMO

BACKGROUND: Cisplatin (DDP) is one of the important chemotherapy drugs for patients with advanced gastric cancer and metastasis, but its resistance is a bottleneck problem that affects clinical efficacy and patient survival. Eremias multiocellata (EM) is a traditional Chinese herbal medicine, which has been used in the treatment of precancerous lesions, gastric cancer, liver fibrosis, and other digestive diseases. However, the mechanism of reducing chemotherapy resistance to gastric cancer is still unclear. METHODS: We used the MTT assay to evaluate the proliferative viability of gastric cancer parental cell line MKN45 and its drug-resistant cell line MKN45/DDP, and compared their drug-resistance indices. The migration and invasion abilities of MKN45/DDP drug-resistant cells were evaluated using the Transwell assay. Apoptosis in MKN45/DDP drug-resistant cells was detected using flow cytometry. The effect of a combination of EM and cisplatin on the levels of reactive oxygen species (ROS) and lipid peroxides (LPO) in cisplatin-resistant gastric cancer cells was detected using ROS fluorescent probes and a lipid peroxidation assay kit in conjunction with flow cytometry. The effect of EM combined with cisplatin on the level of iron ions was detected by fluorescence probe and confocal laser technique. Hematoxylin-eosin staining (HE staining) was used to detect the histopathologic morphology of drug-resistant gastric cancer in nude mice. Ferroptosis-related proteins were measured using immunohistochemistry. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect tumor drug resistance-related genes. The NF-κB/Snail pathway-related proteins, PI3K/AKT/mTOR pathway-related proteins, and drug resistance-related proteins were detected by Western blot. RESULTS AND CONCLUSIONS: The results of in vitro and in vivo experiments showed that EM combined with DDP could effectively inhibit the migration and invasive ability of MKN45/DDP cells, as well as induce apoptosis of MKN45/DDP cells; the combination of the two drugs could significantly increase the levels of ROS, lipid peroxidation and divalent ferric ions in MKN45/DDP cells, at the same time reducing the levels of Ferroptosis-related proteins, which could induce Ferroptosis. In addition, EM combined with DDP can also exert the effect of reversing DDP resistance and increasing the sensitivity of gastric cancer drug-resistant cells to DDP by regulating the NF-κB/Snail signaling pathway, PI3K/AKT/mTOR signaling pathway, and the expression of drug resistance-related proteins and genes.


Assuntos
Cisplatino , Neoplasias Gástricas , Animais , Camundongos , Humanos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Neoplasias Gástricas/genética , Resistencia a Medicamentos Antineoplásicos/genética , NF-kappa B , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos Nus , Fosfatidilinositol 3-Quinases , Espécies Reativas de Oxigênio , Apoptose , Serina-Treonina Quinases TOR , Íons/farmacologia , Íons/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células
2.
J Transl Med ; 21(1): 714, 2023 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-37821919

RESUMO

PURPOSE: Currently, there are no accurate markers for predicting potentially lethal prostate cancer (PC) before biopsy. This study aimed to develop urine tests to predict clinically significant PC (sPC) in men at risk. METHODS: Urine samples from 928 men, namely, 660 PC patients and 268 benign subjects, were analyzed by gas chromatography/quadrupole time-of-flight mass spectrophotometry (GC/Q-TOF MS) metabolomic profiling to construct four predictive models. Model I discriminated between PC and benign cases. Models II, III, and GS, respectively, predicted sPC in those classified as having favorable intermediate risk or higher, unfavorable intermediate risk or higher (according to the National Comprehensive Cancer Network risk groupings), and a Gleason sum (GS) of ≥ 7. Multivariable logistic regression was used to evaluate the area under the receiver operating characteristic curves (AUC). RESULTS: In Models I, II, III, and GS, the best AUCs (0.94, 0.85, 0.82, and 0.80, respectively; training cohort, N = 603) involved 26, 24, 26, and 22 metabolites, respectively. The addition of five clinical risk factors (serum prostate-specific antigen, patient age, previous negative biopsy, digital rectal examination, and family history) significantly improved the AUCs of the models (0.95, 0.92, 0.92, and 0.87, respectively). At 90% sensitivity, 48%, 47%, 50%, and 36% of unnecessary biopsies could be avoided. These models were successfully validated against an independent validation cohort (N = 325). Decision curve analysis showed a significant clinical net benefit with each combined model at low threshold probabilities. Models II and III were more robust and clinically relevant than Model GS. CONCLUSION: This urine test, which combines urine metabolic markers and clinical factors, may be used to predict sPC and thereby inform the necessity of biopsy in men with an elevated PC risk.


Assuntos
Metaboloma , Neoplasias da Próstata , Humanos , Masculino , Biópsia , Gradação de Tumores , Antígeno Prostático Específico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Neoplasias da Próstata/urina , Fatores de Risco , Detecção Precoce de Câncer/métodos , Urinálise/métodos , Urina/química
3.
Biomater Adv ; 151: 213451, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37150081

RESUMO

Indocyanine green (ICG) has been employed in medical diagnostics due to its superior photophysical characteristics. However, these advantages are offset by its quick body clearance and inferior photo-stability. In this work, programmable prodrug carriers for chemotherapy/PDT/PTT against nasopharyngeal carcinoma (NPC) were created in order to increase photo-stability and get around biochemical hurdles. The programmable prodrug carriers (PEG-PLA@DIT-PAMAM) that proactively penetrated deeply into NPC tumors and produced the deep phototherapy and selective drug release under laser irradiation was created by dendrimer-DOX/ICG/TPP (DIT-PAMAM) and PEGylated poly (α-lipoic acid) (PLA) copolymer. Long circulation times and minimal toxicity to mammalian cells are two benefits of PEG-coated carriers. The overexpressed GSH on the tumor cell or vascular endothelial cell of the NPC disintegrated the PEG-g-PLA chains and released the DIT-PAMAM nanoparticles after the carriers had reached the NPC tumor periphery. Small, positively charged DIT-PAMAM nanoparticles may penetrate tumors effectively and remain inside tumor for an extended period of time. In addition, the induced ROS cleaved the thioketal linkers for both DOX and nanoparticles and product hyperthermia (PTT) to kill cancer cells under laser irradiation, facilitating faster diffusion of nanoparticles and more effective tumor penetration with a programmable publication of DOX. The programmable prodrug carries showed high photo-stability high photo-stability, which enabled very effective PDT, PTT, and tumor-specific DOX release. With the goal of combining the effects of chemotherapy, PDT, and PTT against NPC, this research showed the great efficacy of programmable prodrug carriers.


Assuntos
Hipertermia Induzida , Neoplasias Nasofaríngeas , Pró-Fármacos , Animais , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Poliésteres , Mamíferos
4.
Molecules ; 28(4)2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36838824

RESUMO

(E)-7-Phenyl-2-hepten-4,6-diyn-1-ol (1) and (Z)-7-Phenyl-2-hepten-4,6-diyn-1-ol (2) are isomeric natural polyacetylenes isolated from the Chinese medicinal plant Bidens pilosa L. This study first revealed the excellent anti-metastasis potential of these two polyacetylenes on human gastric cancer HGC-27 cells and the distinctive molecular mechanisms underlying their activities. Polyacetylenes 1 and 2 significantly inhibited the migration, invasion, and adhesion of HGC-27 cells at their non-toxic concentrations in a dose-dependent manner. The results of a further mechanism investigation showed that polyacetylene 1 inhibited the expressions of Vimentin, Snail, ß-catenin, GSK3ß, MST1, YAP, YAP/TAZ, and their phosphorylation, and upregulated the expression of E-cadherin and p-LATS1. In addition, the expressions of various downstream metastasis-related proteins, such as MMP2/7/9/14, c-Myc, ICAM-1, VCAM-1, MAPK, p-MAPK, Sox2, Cox2, and Cyr61, were also suppressed in a dose-dependent manner. These findings suggested that polyacetylene 1 exhibited its anti-metastasis activities on HGC-27 cells through the reversal of the EMT process and the suppression of the Wnt/ß-catenin and Hippo/YAP signaling pathways.


Assuntos
Bidens , Neoplasias Gástricas , Humanos , beta Catenina/metabolismo , Polímero Poliacetilênico , Via de Sinalização Hippo , Poli-Inos , Via de Sinalização Wnt
5.
Curr Med Sci ; 40(4): 597-601, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32767260

RESUMO

In late December 2019, COVID-19 was firstly recognized in Wuhan, China and spread rapidly to all of the provinces of China. The West Campus of Wuhan Union Hospital, the designated hospital to admit and treat the severe and critically ill COVID-19 cases, has treated a large number of such patients with great success and obtained lots of valuable experiences based on the Chinese guideline (V7.0). To standardize and share the treatment procedures of severe and critically ill cases, Wuhan Union Hospital has established a working group and formulated an operational recommendation, including the monitoring, early warning indicators, and several treatment principles for severe and critically ill cases. The treatment experiences may provide some constructive suggestions for treating the severe and critically ill COVID-19 cases all over the world.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticoagulantes/uso terapêutico , Antivirais/uso terapêutico , COVID-19 , Teste para COVID-19 , China/epidemiologia , Técnicas de Laboratório Clínico , Terapia Combinada , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Estado Terminal , Dexametasona/uso terapêutico , Hospitais , Humanos , Imunização Passiva , Medicina Tradicional Chinesa , Pandemias , Pneumonia Viral/epidemiologia , Terapia Respiratória/métodos , SARS-CoV-2 , Tratamento Farmacológico da COVID-19 , Soroterapia para COVID-19
6.
Urologia ; 87(2): 65-69, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-30868937

RESUMO

OBJECTIVE: To investigate the safety and efficacy of the combination of suprapubic prostatectomy with transurethral resection of the prostate (TURP) for the treatment of large volume benign prostatic hyperplasia (BPH). METHODS: We retrospectively analyzed the clinical data of two methods of treatment with 60 cases of a large volume BPH (>100 g) from January 2011 to 2017; the methods were suprapubic prostatectomy and suprapubic prostatectomy combination with TURP, in which the single open group comprised 30 cases, treated using the former method, and the combined open group comprised the other 30 cases, treated using the latter method. In the combined open group, the residual prostate gland was removed by TURP. We compared both the groups of patients using age, prostate volume, international prostate symptom score (IPSS), prostate-specific antigen (PSA), maximum flow rate, residual urine, operation time, hospitalization time, postoperative washing time, blood transfusion rate, and decreased amount of intraoperative hemoglobin in operation, and compared the preoperative and postoperative IPSS, maximum flow rate, and residual urine volume. RESULTS: There was no significant difference between the two groups in age, prostate volume, IPSS, PSA, maximum flow rate, residual urine, and other clinical data (P > 0.05); the single group operation time, postoperative bladder irrigation time, hospitalization time, blood transfusion rate, and decreased amount of intraoperative hemoglobin were significantly greater in the single open group than in the combined open group, and statistically significant differences were observed between both the groups (P < 0.05). Postoperative voiding function improved significantly compared with the preoperative, and a statistically significant difference was observed (P < 0.05). CONCLUSION: The combination of suprapubic prostatectomy with TURP is an effective and a safe surgical method for the treatment of patients with large volume BPH. It is certainly worthy of clinical application.


Assuntos
Prostatectomia/métodos , Hiperplasia Prostática/cirurgia , Idoso , Terapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Prostatectomia/efeitos adversos , Hiperplasia Prostática/patologia , Estudos Retrospectivos , Ressecção Transuretral da Próstata/efeitos adversos , Resultado do Tratamento
7.
Acta Pharmaceutica Sinica ; (12): 922-929, 2020.
Artigo em Chinês | WPRIM | ID: wpr-821692

RESUMO

Schisandrol B (SolB) is one of the active constituents from a traditional Chinese medicine Schisandra chinensis or Schisandra sphenanthera. Our previous studies found that SolB exerts hepatoprotective effects against drug-induced liver injury and promotes liver regeneration. We further found that SolB significantly induces liver enlargement but the mechanisms remain unclear. The purpose of this study was to investigate the change of lipidome in liver tissues during SolB-induced hepatomegaly. The animal experiment protocol was approved by the Institutional Animal Care and Use Committee at Sun Yat-sen University. Serum and liver samples of male C57BL/6 mice were collected after intraperitoneal injection of SolB (100 mg·kg-1·d-1) for 5 days. Lipidomics analysis was performed using Q Exactive UHPLC-MS/MS system. The results showed that SolB significantly promoted liver enlargement in mice without liver injury and inflammation. Lipid accumulation was observed in the liver tissues after SolB treatment. Thirty-five lipids were identified with significant change and triglycerides (TG) were found to have the most significant increase in SolB-treated group, indicating the increase of energy production during SolB-induced hepatomegaly. This study reveals the impact of SolB on lipid metabolism and provides a potential explanation for liver enlargement induced by SolB.

8.
Fitoterapia ; 138: 104294, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31398449

RESUMO

Two new eremophilane-type sesquiterpenes, carperemophilanes A and B (1-2), three new maleimide-bearing compounds, carpesiumaleimides A-C (3-5), along with a known sesquiterpene, carabrol (6), were isolated from the ethanol extract of Carpesium abrotanoides L. Their structures were elucidated by analysis of their NMR and MS data as well as by comparison with the literature. The absolute configuration of carperemophilane A (1) was determined by single-crystal X-ray diffraction analysis. All isolated compounds (1-6) were evaluated in vitro for cytotoxicity against two human cancer cell lines MDA-MB-231 and HGC-27 using the MTT method. Compounds 1, 2 and 6 showed cytotoxic activities with IC50 values ranging from 7.45 to 37.35 µM.


Assuntos
Asteraceae/química , Maleimidas/farmacologia , Sesquiterpenos/farmacologia , Linhagem Celular Tumoral , China , Humanos , Maleimidas/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Sesquiterpenos/isolamento & purificação
9.
Curr Med Sci ; 39(2): 211-216, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31016512

RESUMO

Discontinuation of tyrosine kinase inhibitor (TKI) therapy after achieving a persistent deep molecular response (DMR) is an urgently needed treatment goal for chronic myeloid leukemia (CML) patients and has been included in the National Comprehensive Cancer Network (NCCN) guidelines (version 2.2017) for CML. Indeed, various studies have confirmed the feasibility of discontinuing TKI therapy. In this study, we analyzed data from 45 CML patients who had discontinued TKI therapy. Univariate analysis was performed to predict factors that were potentially related to treatment-free remission (TFR) and identify the differences between early relapse and late relapse. Out of the 45 patients, 20 exhibited molecular relapse after a median follow-up of 18 months (range, 1-54 months), and the estimated TFR at 24 months was 40%. The univariate analysis revealed that a high Sokal score and interruptions or dose reductions during TKI treatment were the only baseline factors associated with poor outcomes. Our results indicate that TKI discontinuation could be successfully put into practice in China.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Adolescente , Adulto , Idoso , Povo Asiático , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
Fitoterapia ; 127: 349-355, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29621599

RESUMO

Five new guaiane-type sesquiterpene lactones, caroguaianolide A-E (1-5), along with nine known sesquiterpene lactones (6-14) were isolated from the whole plant of Carpesium abrotanoides L. Their structures were elucidated on the basis of spectroscopic date, HRESIMS analysis, and comparison of experimental and calculated ECD data. All isolated compounds (1-14) were tested in vitro for their cytotoxic activities against the MDA-MB-231, HGC-27 cancer cell lines, of which compounds 1-3, 6, 7, 11 and 12 showed significant cytotoxic activities with IC50 values ranging from 2.67 to 12.34 µM.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Asteraceae/química , Lactonas/isolamento & purificação , Sesquiterpenos de Guaiano/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Humanos , Lactonas/farmacologia , Estrutura Molecular , Sesquiterpenos de Guaiano/farmacologia
11.
Naunyn Schmiedebergs Arch Pharmacol ; 389(6): 573-84, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26935715

RESUMO

Cervical cancer is the second leading cause of cancer deaths in women worldwide. In recent years, the studies find that inflammation is a critical component of tumor progression, and the ideal therapeutic methods should be aimed at the inflammation reaction triggers. (1ß,3ß,5ß,25S)-spirostan-1,3-diol1-[α-L-rhamnopyranosyl-(1 → 2)-ß-D-xylopyranoside] (RCE-4) was the main active composition of Reineckia carnea (Andr.) Kunth. It significantly induced apoptosis in cervical cancer Caski cells through the mitochondrial pathway in our previous studies; however, its underlying mechanism remains poorly understood. This study aimed to further evaluate the effect of RCE-4 on human cervical cancer HeLa cells. Based on this observation, we investigated the anti-cervical cancer effect of RCE-4 by modulating phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway, nuclear factor-kappa B (NF-κB) activation, and inflammation-related key factors in HeLa cells. The results indicated that the HeLa cell was the most sensitive with an IC50 of 7.01 µM; RCE-4 significantly promoted the release of cellular lactate dehydrogenase (LDH); increased DNA fragmentation and apoptosis; reduced PI3K, Akt, mTOR, and NF-κBp65 phosphorylation levels; increased the Bax and cleaved poly (ADP-ribose) polymerase (PARP) protein levels; suppressed Bcl-2 protein expression; elevated the Bax/Bcl-2 expression ratio; and decreased the interleukin-1 beta (IL-1ß) and interleukin-6 (IL-6) mRNA expressions in HeLa cells in a concentration-dependent manner. These findings suggest that RCE-4 exerted beneficially anti-cervical cancer effect on HeLa cells, mainly inhibiting PI3K/Akt/mTOR signaling pathway phosphorylation and NF-κB activation, promoting HeLa cell apoptosis. Graphical abstract Anti-tumor effect of RCE-4 on HeLa cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Proliferação de Células/efeitos dos fármacos , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Saponinas/farmacologia , Espirostanos/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Ativação Enzimática , Feminino , Células HeLa , Humanos , Mediadores da Inflamação/metabolismo , Concentração Inibidora 50 , L-Lactato Desidrogenase/metabolismo , Liliaceae/química , Células MCF-7 , Fosforilação , Fitoterapia , Plantas Medicinais , Saponinas/isolamento & purificação , Transdução de Sinais/efeitos dos fármacos , Espirostanos/isolamento & purificação , Neoplasias do Colo do Útero/enzimologia , Neoplasias do Colo do Útero/patologia
12.
PLoS One ; 10(2): e0116372, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25671650

RESUMO

Alterations in microtubule-dependent trafficking and certain signaling pathways in neuronal cells represent critical pathogenesis in neurodegenerative diseases. Huntingtin (Htt)-associated protein-1 (Hap1) is a brain-enriched protein and plays a key role in the trafficking of neuronal surviving and differentiating cargos. Lack of Hap1 reduces signaling through tropomyosin-related kinases including extracellular signal regulated kinase (ERK), resulting in inhibition of neurite outgrowth, hypothalamic dysfunction and postnatal lethality in mice. To examine how Hap1 is involved in microtubule-dependent trafficking and neuronal differentiation, we performed a proteomic analysis using taxol-precipitated microtubules from Hap1-null and wild-type mouse brains. Breakpoint cluster region protein (Bcr), a Rho GTPase regulator, was identified as a Hap1-interacting partner. Bcr was co-immunoprecipitated with Hap1 from transfected neuro-2a cells and co-localized with Hap1A isoform more in the differentiated than in the nondifferentiated cells. The Bcr downstream effectors, namely ERK and p38, were significantly less activated in Hap1-null than in wild-type mouse hypothalamus. In conclusion, Hap1 interacts with Bcr on microtubules to regulate neuronal differentiation.


Assuntos
Diferenciação Celular , Proteínas do Tecido Nervoso/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-bcr/metabolismo , Animais , Diferenciação Celular/genética , Linhagem Celular , Feminino , Hipotálamo/metabolismo , Camundongos , Camundongos Knockout , Microtúbulos/metabolismo , Proteínas do Tecido Nervoso/genética , Ligação Proteica , Transporte Proteico , Proteínas Proto-Oncogênicas c-bcr/genética , Transdução de Sinais
13.
Zhongguo Zhong Yao Za Zhi ; 40(22): 4424-7, 2015 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-27097418

RESUMO

Chemical constituents of 95% ethanol extract of the dried persistent calyx of Physalis pubescens were investigated. By chromatography on a silica gel column and reverse-phase preparative HPLC, 10 compounds were isolated from the dichloromethane fraction. Based on the MS and 1D/2D NMR data, these compounds were identified as 5-O-(E-feruloyl) blumenol (1), isovanillin (2), (E) -ethyl 3-(4-hydroxyphenyl) acrylate (3), 4-hydroxybenzaldehyde(4), 4-methylphenol (5), (E) -methyl cinnamate (6), 7,3',4' trimethoxyquercetin (7), 5,3', 5'-trihydroxy-3,7,4'-trimethoxyflavone(8), danielone (9), and 5,5'-diisobutoxy-2,2'-bifuran (10).


Assuntos
Medicamentos de Ervas Chinesas/química , Physalis/química , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/isolamento & purificação , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray
14.
Fitoterapia ; 95: 93-101, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24637110

RESUMO

Hispolon was the main antitumor active ingredient in Phellinus sensu lato species. In order to confirm the dual regulating estrogenic ingredient and obtain more effective natural estrogen replacement drugs, hispolon was separated from Phellinus lonicerinus (Bond.) Bond. et sing. Hispolon exhibited significant anti-proliferative effect against estrogen-sensitive ER (+) MCF-7 cells in the absence of estrogen, and exhibits antagonistic effects on 17ß-estradiol (E2)-induced MCF-7 cell proliferation when E2 and the different concentrations of hispolon were treated simultaneously. Hispolon also inhibited the proliferation of estrogen-negative ER (-) MDA-MB-231 cells at the concentration of 5.00×10(-5) M. The yeast two-hybrid experiments showed that hispolon had strong and non-selective effects on the estrogen receptor (ER) α and ERß at a concentration of 1.00×10(-6) M. The ERß-binding ability of hispolon was larger than ERα in the concentration range of 1.00×10(-9) M and 1.00×10(-7) M. Hispolon could increase the body weight coefficient, serum E2 and progesterone contents in immature female mice at dose of 9.10×10(-6) mol/kg, and increase coefficient of thymus and spleen in mice. The Gscores of hispolon-ERα and hispolon-ERß docked complexes were -7.93 kcal/mol and -7.79 kcal/mol in docking simulations. Hispolon presented dual regulating estrogenic activities, which showed estrogenic agonist activity at low concentration or lack of endogenous estrogen, and the estrogenic antagonistic effect was stimulated at high concentrations or too much endogenous estrogen. Hispolon could be used for treating the estrogen deficiency-related disease with the benefit of non-toxic to normal cells, good antitumor effects and estrogenic activity.


Assuntos
Basidiomycota/química , Catecóis/farmacologia , Antagonistas de Estrogênios/farmacologia , Estrogênios/agonistas , Animais , Peso Corporal , Catecóis/química , Catecóis/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Antagonistas de Estrogênios/química , Antagonistas de Estrogênios/isolamento & purificação , Receptor alfa de Estrogênio/química , Estrogênios/deficiência , Feminino , Genes Reporter , Humanos , Camundongos , Modelos Moleculares , Simulação de Acoplamento Molecular , Baço/efeitos dos fármacos , Timo/efeitos dos fármacos , Técnicas do Sistema de Duplo-Híbrido
15.
Artigo em Chinês | WPRIM | ID: wpr-330265

RESUMO

<p><b>OBJECTIVE</b>To investigate the protective effect and action mechanism of petroleum ether extracts from Saussurea involucrate on brain tissues of hypoxia rats under constant pressure and closed conditions.</p><p><b>METHOD</b>The PESI dosage-dependent experiment for hypoxia rats was conducted under constant pressure and closed conditions by intraperitoneally injecting 125, 250, 500 mg x kg(-1) to finalize that the optimum dosage is the high dose of PESI. Afterwards, 90 Wistar rats were randomly divided into the hypoxic model group, the acetazolamide 250 mg x kg(-1) group and the PESI high dose group. Each group was further divided into three subgroups according to different hypoxia times, with 10 rats in each subgroup. Under the same hypoxia and administration conditions, the rats were sacrificed after 0, 3, 6 h respectively. Their brain samples were collected for common pathological observation and immunohistochemical staining of HIF-1alpha. Real-time RT-PCR was used to detect HIF-1alpha, EPO, HO-1 and Caspase-3 gene expressions. And the Western blot assay was adopted to detect HIF-1alpha protein expression.</p><p><b>RESULT</b>The brain tissues of the hypoxia model group were severely damaged with the increase in the hypoxia time. The acetazolamide group and the PESI high does group were damaged in a much lower degree. According to the gene expression and the Western blot assay, high dose of PESI could inhibit HIF-1alpha expression. According to the pure gene expression test, high dose of PESI could increase EPO and HO-1 mRNA expressions, but inhibit Caspase-3 mRNA expression.</p><p><b>CONCLUSION</b>PESI's protective mechanism for brain tissues of hypoxia rats under constant pressure and closed conditions may be related to its effects in inhibiting HIF-1alpha expression, increasing EPO expression and resisting cell apoptosis.</p>


Assuntos
Animais , Masculino , Ratos , Alcanos , Química , Encéfalo , Biologia Celular , Metabolismo , Caspase 3 , Genética , Hipóxia Celular , Citoproteção , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas , Farmacologia , Eritropoetina , Genética , Regulação Enzimológica da Expressão Gênica , Heme Oxigenase-1 , Genética , Subunidade alfa do Fator 1 Induzível por Hipóxia , Genética , Metabolismo , Ratos Wistar , Saussurea , Química
16.
Chin Med J (Engl) ; 126(7): 1220-3, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23557547

RESUMO

BACKGROUND: A virtual reality simulator provides a novel training model for improving surgical skills in a variety of fields. They can simulate a variety of surgical scenarios to improve the overall skills required for endoscopic operations, and also record the operative process of trainees in real-time and allow for objective evaluation. At present, some simulators for transurethral resection of the prostate (TURP) are available. The utility of virtual reality simulators in training of transurethral prostatectomy was investigated. METHODS: Thirty-eight urologists were randomly selected to take part in a simulation based training of TURP using the TURPSim(TM) system. Pre and post-training global rate scale (GRS) scores and objective parameters recorded by the simulator were assessed. Then, questionnaires were filled out. RESULTS: Compared with baseline levels, the GRS scores of trainees increased (18.0 ± 4.0 vs. 12.4 ± 4.2, P < 0.001), while the rate of capsule resection (26.3% ± 0.6% vs. 21.2% ± 0.4%, P < 0.001), amount of blood loss ((125.8 ± 86.3) ml vs. (83.7 ± 41.6) ml, P < 0.001), external sphincter injury (3.6 ± 2.9 vs. 2.0 ± 2.0, P < 0.001) decreased significantly after training. Most trainees were satisfied with the simulator based training and believed that the simulator accurately mimicked actual surgical procedures and could help improve their surgical skills. CONCLUSIONS: As a new method of training on transurethral prostatectomy skills, training of TURP using a virtual simulator can help urologists improve their surgical skills and safety. Therefore, the application of the TURPSim(TM) system in education and training of urologic surgery is warranted.


Assuntos
Simulação por Computador , Ressecção Transuretral da Próstata/educação , Procedimentos Cirúrgicos Urológicos/educação , Adulto , Humanos , Masculino , Urologia/educação
17.
Nat Prod Res ; 27(2): 123-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22502647

RESUMO

Three new furostanol saponins (1-3), including a polyhydroxyl saponin, were isolated from the rhizomes of Tupistra chinensis. The structures of these compounds were identified by NMR, MS spectral data and chemical methods.


Assuntos
Liliaceae/química , Extratos Vegetais/análise , Rizoma/química , Saponinas/análise , Esteróis/análise , Cromatografia em Camada Fina , Hidrólise , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Extratos Vegetais/isolamento & purificação , Saponinas/isolamento & purificação , Esteróis/isolamento & purificação
18.
Nat Prod Res ; 27(2): 85-92, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22304302

RESUMO

Two new spirostanols and a new furostanol, reinocarnoside A (1), B (2) and C (3), were isolated from the roots of Reineckia carnea, together with two known compounds, (25S)-1ß,3ß,4ß-trihydroxyspirostan-5ß-yl-O-ß-D-glucopyranoside (4), kitigenin-5ß-O-ß-D-glucopyranoside (5). The structures of three new compounds were elucidated by spectroscopic methods including 1-D NMR, 2-D NMR and MS spectrums, and their anticancer activities were evaluated by MTT method.


Assuntos
Antineoplásicos/farmacologia , Glicosídeos/análise , Liliaceae/química , Extratos Vegetais/análise , Raízes de Plantas/química , Espirostanos/análise , Esteróis/análise , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Células Hep G2/efeitos dos fármacos , Humanos , Células MCF-7/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Espirostanos/isolamento & purificação , Espirostanos/farmacologia , Esteróis/isolamento & purificação , Esteróis/farmacologia , Sais de Tetrazólio , Tiazóis
19.
Chinese Medical Journal ; (24): 1220-1223, 2013.
Artigo em Inglês | WPRIM | ID: wpr-342201

RESUMO

<p><b>BACKGROUND</b>A virtual reality simulator provides a novel training model for improving surgical skills in a variety of fields. They can simulate a variety of surgical scenarios to improve the overall skills required for endoscopic operations, and also record the operative process of trainees in real-time and allow for objective evaluation. At present, some simulators for transurethral resection of the prostate (TURP) are available. The utility of virtual reality simulators in training of transurethral prostatectomy was investigated.</p><p><b>METHODS</b>Thirty-eight urologists were randomly selected to take part in a simulation based training of TURP using the TURPSim(TM) system. Pre and post-training global rate scale (GRS) scores and objective parameters recorded by the simulator were assessed. Then, questionnaires were filled out.</p><p><b>RESULTS</b>Compared with baseline levels, the GRS scores of trainees increased (18.0 ± 4.0 vs. 12.4 ± 4.2, P < 0.001), while the rate of capsule resection (26.3% ± 0.6% vs. 21.2% ± 0.4%, P < 0.001), amount of blood loss ((125.8 ± 86.3) ml vs. (83.7 ± 41.6) ml, P < 0.001), external sphincter injury (3.6 ± 2.9 vs. 2.0 ± 2.0, P < 0.001) decreased significantly after training. Most trainees were satisfied with the simulator based training and believed that the simulator accurately mimicked actual surgical procedures and could help improve their surgical skills.</p><p><b>CONCLUSIONS</b>As a new method of training on transurethral prostatectomy skills, training of TURP using a virtual simulator can help urologists improve their surgical skills and safety. Therefore, the application of the TURPSim(TM) system in education and training of urologic surgery is warranted.</p>


Assuntos
Adulto , Humanos , Masculino , Simulação por Computador , Ressecção Transuretral da Próstata , Educação , Procedimentos Cirúrgicos Urológicos , Educação , Urologia , Educação
20.
Zhonghua Wai Ke Za Zhi ; 50(2): 157-60, 2012 Feb 01.
Artigo em Chinês | MEDLINE | ID: mdl-22490357

RESUMO

OBJECTIVE: To evaluate the face and content validation of the virtual reality transurethral resection of the prostate simulator (TURPSim(TM)). METHODS: The 60 urology doctor aged 26 - 50 years old all over the country were enrolled for virtual reality training of TURP from September 2010 to June 2011. Participants classified as experts (more than 50 procedures performed) and novices (50 or fewer procedures performed) performed TURPs on TURPSim(TM) involving resection of 25 - 80 g prostate. They completed questionnaires regarding utility for residency training, realism and overall score of the TURPSim(TM). Performances of two groups were evaluated after 2-day training. RESULTS: were recorded and analyzed. RESULTS: Mean utility for residency training, realism and overall score were (8.8 ± 1.1) and (8.5 ± 1.4), (8.0 ± 1.2) and (8.4 ± 1.1), (8.7 ± 0.9) and (8.6 ± 0.8) in experts and novices respectively. There was no significant difference between two groups (P > 0.05). Spearman's correlation coefficients analysis showed an significant positive correlation between utility for residency training and realism (r = 0.625, P = 0.000), utility for residency training and overall score (r = 0.691, P = 0.000) in experts, utility for residency training and realism (r = 0.702, P = 0.000), utility for residency training and overall score (r = 0.664, P = 0.001) in novices. Prostate resection rate (87.3% ± 7.7%), bleeding control rate (94.4% ± 6.6%) and safety (95.2% ± 5.5%) in novices increased after training (t = -3.689, -2.274, -2.507, all P < 0.05). CONCLUSIONS: The face and content validation of transurethral resection of the prostate simulator is good, virtual reality training of TURP may improve the skills necessary to perform TURP. Transurethral resection of the prostate simulator can be used to train urology residents.


Assuntos
Simulação por Computador , Ressecção Transuretral da Próstata/métodos , Urologia/educação , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Ressecção Transuretral da Próstata/educação , Urologia/métodos
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