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1.
Artigo em Inglês | MEDLINE | ID: mdl-38185388

RESUMO

PURPOSE: The aim of this work was to determine whether locally advanced rectal cancer (LARC) with negative mesorectal fascia (MRF) predicted by magnetic resonance imaging (MRI) can be excluded from preoperative radiation therapy treatment. METHODS AND MATERIALS: This multicenter, open-label, non-inferiority, randomized clinical trial enrolled patients with LARC within 6 to 12 cm from the anal verge and with negative MRI-predicted MRF. Participants were randomized to the intervention group (primary surgery, in which the patients with positive pathologic [CRM] circumferential margins were subjected to chemoradiotherapy [CRT] and those with negative CRM underwent adjuvant chemotherapy according to pathologic staging) or the control group (preoperative CRT, in which all patients underwent subsequent surgery and adjuvant chemotherapy). The primary endpoint was 3-year disease-free survival (DFS). RESULTS: A total of 275 patients were randomly assigned to the intervention (n = 140) and control (n = 135) groups, in which 33.57% and 28.15% patients were at clinical T4 stage and 85.92% and 80.45% patients were at "bad" or "ugly" risk in the intervention and control groups, respectively. There were 2 patients (1.52%) and 1 patient (0.77%) with positive CRM in the intervention and control groups, respectively (P > .05). The non-adherence rates for the intervention and control groups were 3.6% and 23.7%, respectively. After a median follow-up of 34.6 months (IQR, 18.2-45.7), 43 patients had positive events (28 patients and 15 patients in the intervention and control groups, respectively). There were 6 patients (4.4%) with local recurrence in the intervention group and none in the control group, which led to the termination of the trial. The 3-year DFS rate was 81.82% in the intervention group (95% CI, 78.18%-85.46%) and 85.37% in the control group (95% CI, 81.75%-88.99%), with a difference of -3.55% (95% CI, -3.71% to -3.39%; hazard ratio, 1.76; 95% CI, 0.94-3.30). In the per-protocol data set, the difference between 3-year DFS rates was -5.44% (95% CI, -5.63% to -5.25%; hazard ratio, 2.02; 95% CI, 1.01-4.06). CONCLUSIONS: Based on the outcomes of this trial, in patients with LARC and MRI-negative MRF, primary surgery could negatively influence their DFS rates. Therefore, primary surgery was an inferior strategy compared with preoperative CRT followed by surgery and cannot be recommended for patients with LARC.

2.
Fitoterapia ; 173: 105808, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38168567

RESUMO

Four new steroidal glycosides (1-4), including two steroidal saponins named lililancifoloside B and C (1-2), one pregnane glycoside named lililancifoloside D (3), and one C22-steroidal lactone glycoside named lililancifoloside E (4), together with five known ones (5-9), were isolated from the bulbs of Lilium lancifolium Thunb. By using spectroscopic analysis, including 1D, 2D NMR, and HR-ESI-MS, the structures of 1-4 were elucidated. All isolates were tested for their cytotoxic potential against the MCF-7, MDA-MB-231, HepG2, and A549 cell lines. Compound 6 distinguished out among them, IC50 values of 3.31, 5.23, 1.78, and 1.49 µM against the four cell lines, respectively. Other compounds such as compound 3, 5, and 9 have also shown specific cytotoxic activity. Next, studies showed that compound 6 might cause HepG2 cells to undergo a cell cycle arrest during the G2/M phase and apoptosis.


Assuntos
Lilium , Saponinas , Lilium/química , Estrutura Molecular , Glicosídeos/farmacologia , Glicosídeos/química , Saponinas/farmacologia , Extratos Vegetais/química
3.
Front Psychol ; 14: 1248729, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38655499

RESUMO

Background: Nowadays, e-learning significantly affects college students' academic life. This study aims to examine the factors that influence college students' satisfaction with online learning outcomes. Method: The study population consisted of undergraduate students from Dalian Medical University, with a total of 715 college students participating in the study. Out of these participants, 602 valid questionnaires were obtained. Demographic data was analyzed using SPSS.22, and the data was cleaned and prepared for testing the research hypotheses. The proposed research framework was examined using structural equation modeling (SEM) through Smart-PLS 3.0. Results: The results of the study showed that student satisfaction with learning outcomes was positively correlated with several factors: quality of teacher instruction (ß = 0.100, p < 0.0001), quality of e-learning platforms (ß = 0.059, p < 0.0001), individual learner factors such as learning motivation (ß = 0.112, p < 0.001), and e-learning environment (ß = 0.469, p < 0.001). Additionally, self-learning efficacy (ß = 0.081, p < 0.0001), learning strategies (ß = 0.031, p < 0.001), and learning motivation (ß = 0.039, p < 0.001) were found to have mediating effects. Conclusion: Understanding the satisfaction of college students with the effect of e-learning holds great significance in coping with teaching methods in unexpected situations. It enables adjustments to teaching strategies, improvements to learning platforms, and mobilization of students' motivation. Thus, it serves as a valuable reference in addressing unexpected teaching scenarios.

4.
Artigo em Inglês | MEDLINE | ID: mdl-36159907

RESUMO

Objective: To investigate the risk factors for lateral lymph node metastasis (LLNM) in papillary thyroid carcinoma (PTC). Methods: A retrospective analysis of 209 patients with PTC who underwent primary surgery at the Beijing Friendship Hospital affiliated with Capital Medical University from November 2014 to November 2018 was performed. The patients were divided into the LLNM group and the non-LLNM group. The clinical and pathological characteristics of the patients were analysed. The risk factors for LLNM were analysed by univariate and multivariate analyses. Results: The incidence of LLNM was 13.4% in PTC patients. Univariate analysis showed that the maximum diameter of the primary tumour > 2 cm (P < 0.001), bilateral primary tumour (P = 0.020), extrathyroidal extension (ETE) (P < 0.001), central lymph node metastasis (CLNM) (P < 0.001), and CLNM number ≥ 5 (P < 0.001) were significantly associated with LLNM. Multivariate logistic regression analysis showed that the maximum diameter of the primary tumour > 2 cm, ETE, and CLNM were independent risk factors for LLNM (OR values were 3.880, 5.202, and 4.474, respectively). There were 6 patients with skip lateral cervical lymph node metastasis, accounting for 21% of all LLNM patients. Conclusion: This study revealed several independent risk factors for predicting LLNM in PTC patients, such as the maximum diameter of the primary tumour > 2 cm, ETE and CLNM. Lateral neck dissection may be recommended in PTC patients with those risk factors. Paying attention to the occurrence of skip lateral cervical lymph node metastasis during the clinical diagnosis and treatment processes is necessary.

5.
Chin J Nat Med ; 19(1): 63-69, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33516453

RESUMO

Two new triterpenoid saponins, ardisicrenoside R and S (1 and 2), and one new phenylpropanoid glycoside, ardicrephenin (3), along with five known compounds (4-8), were isolated from roots of Ardisia crenata. Their structures were elucidated on the basis of NMR spectroscopic data and chemical methods. Compounds 2-7 were evaluated for their cytotoxic activities against A549, MCF-7, HepG2 and MDA-MB-231 cell lines by MTT assay. Ardicrenin (6) showed significant cytotoxicity, with IC50 values of 1.17 ± 0.01, 1.19 ± 0.06, 3.52 ± 0.23, and 16.61 ± 1.02 µmol·L-1, respectively.


Assuntos
Antineoplásicos Fitogênicos , Ardisia , Glicosídeos , Saponinas , Triterpenos , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Ardisia/química , Linhagem Celular Tumoral , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química , Saponinas/isolamento & purificação , Saponinas/farmacologia , Triterpenos/isolamento & purificação , Triterpenos/farmacologia
6.
J Nat Prod ; 84(3): 616-629, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33381964

RESUMO

Thirty-two new diosgenin derivatives were designed, synthesized, and evaluated for their cytotoxic activities in three human cancer cell lines (A549, MCF-7, and HepG2) and normal human liver cells (L02) using an MTT assay in vitro. Most compounds, especially 8, 18, 26, and 30, were more potent when compared with diosgenin. The structure-activity relationship results suggested that the presence of a succinic acid or glutaric acid linker, a piperazinyl amide terminus, and lipophilic cations are all beneficial for promoting cytotoxic activity. Notably, compound 8 displayed excellent cytotoxic activity against HepG2 cells (IC50 = 1.9 µM) and showed relatively low toxicity against L02 cells (IC50 = 18.6 µM), showing some selectivity between normal and tumor cells. Studies on its cellular mechanism of action showed that compound 8 induces G0/G1 cell cycle arrest and apoptosis in HepG2 cells. Predictive studies indicated that p38α mitogen-activated protein kinase (MAPK) is the optimum target of 8 based on its 3D molecular similarity, and docking studies showed that compound 8 fits well into the active site of p38α-MAPK and forms relatively strong interactions with the surrounding amino acid residues. Accordingly, compound 8 may be used as a promising lead compound for the development of new antitumor agents.


Assuntos
Antineoplásicos/farmacologia , Diosgenina/química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Diosgenina/farmacologia , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade
7.
J Nat Prod ; 83(9): 2578-2586, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32822186

RESUMO

Celastrol, a friedelane-type triterpenoid isolated from the genus Triperygium, possesses antitumor, anti-inflammatory, and immunosuppressive activities. A total of 42 celastrol derivatives (1a-1t, 2a-2l, and 3a-3j) were synthesized and evaluated for their immunosuppressive activities. Compounds 2a-2e showed immunosuppressive effects, with IC50 values ranging from 25 to 83 nM, and weak cytotoxicity (CC50 > 1 µM). Compound 2a, with a selectivity index value 31 times higher than that of celastrol, was selected as a lead compound. Further research showed that 2a exerted its immunosuppressive effects by inducing apoptosis and inhibiting cytokine secretion via Lck- and ZAP-70-mediated signaling pathways.


Assuntos
Imunossupressores/síntese química , Imunossupressores/farmacologia , Triterpenos Pentacíclicos/síntese química , Triterpenos Pentacíclicos/farmacologia , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Citocinas/antagonistas & inibidores , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Transdução de Sinais/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Proteína-Tirosina Quinase ZAP-70/efeitos dos fármacos
8.
Steroids ; 155: 108557, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31866546

RESUMO

Two novel steroidal saponins, timosaponin V and W (1 and 2), together with seven known steroidal saponins (3-9), were isolated from the rhizomes of Anemarrhena asphodeloides Bunge. Their structures were elucidated by extensive 1D NMR and 2D NMR (HSQC, HMBC, 1H-1H COSY, and NOESY), and MS analyses. The cytotoxic activities of the isolates were evaluated. Compound 1 showed a significant cytotoxic activity against MCF-7 and HepG2 cell lines with IC50 values of 2.16 ± 0.19 µM and 2.01 ± 0.19 µM, respectively.


Assuntos
Anemarrhena/química , Antineoplásicos Fitogênicos/farmacologia , Rizoma/química , Saponinas/farmacologia , Esteroides/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Células MCF-7 , Modelos Moleculares , Estrutura Molecular , Saponinas/química , Saponinas/isolamento & purificação , Esteroides/química , Esteroides/isolamento & purificação , Relação Estrutura-Atividade , Células Tumorais Cultivadas
9.
BMC Cancer ; 19(1): 988, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31647032

RESUMO

BACKGROUND: Laparoscopic surgery, fast-track perioperative treatment and XELOX chemotherapy are effective strategies for shortening the duration of hospital stay for cancer patients. This trial aimed to clarify the safety and efficacy of the fast-track multidisciplinary treatment (FTMDT) model compared to conventional surgery combined with chemotherapy in Chinese colorectal cancer patients. METHODS: This trial was a prospective randomized controlled study with a 2 × 2 balanced factorial design and was conducted at six hospitals. Patients in group 1 (FTMDT) received fast-track perioperative treatment and XELOX adjuvant chemotherapy. Patients in group 2 (conventional treatment) received conventional perioperative treatment and mFOLFOX6 adjuvant chemotherapy. Subgroups 1a and 2a had laparoscopic surgery and subgroups 1b and 2b had open surgery. The primary endpoint was total length of hospital stay during treatment. RESULTS: A total of 374 patients were randomly assigned to the four subgroups, and 342 patients were finally analyzed, including 87 patients in subgroup 1a, 85 in subgroup 1b, 86 in subgroup 2a, and 84 in subgroup 2b. The total hospital stay of group 1 was shorter than that of group 2 [13 days, (IQR, 11-17 days) vs. 23.5 days (IQR, 15-42 days), P = 0.0001]. Compared to group 2, group 1 had lower surgical costs, fewer in-hospital complications and faster recovery (all P < 0.05). Subgroup 1a showed faster surgical recovery than that of subgroup 1b (all P < 0.05). There was no difference in 5-year overall survival between groups 1 and 2 [87.1% (95% CI, 80.7-91.5%) vs. 87.1% (95% CI, 80.8-91.4%), P = 0.7420]. CONCLUSIONS: The FTMDT model, which integrates laparoscopic surgery, fast-track treatment, and XELOX chemotherapy, was the superior model for enhancing the recovery of Chinese patients with colorectal cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01080547 , registered on March 4, 2010.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Laparoscopia , Idoso , Capecitabina , Quimioterapia Adjuvante , Neoplasias Colorretais/patologia , Custos e Análise de Custo , Desoxicitidina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Tempo de Internação , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/uso terapêutico , Oxaloacetatos , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento
10.
Nat Prod Res ; 33(19): 2755-2761, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30453752

RESUMO

Timosaponin B III is a major bioactive steroidal saponin isolated from Anemarrhena asphodeloides Bge. To potentially discover derivatives with better biological activity, timosaponin B III was structurally modified via acid hydrolysis to yield one new (2, timopregnane A I) C21 steroidal glycoside and seven known compounds. Their structures were elucidated on the basis of NMR spectroscopy and mass spectrometry. All eight compounds were evaluated for cytotoxic activity against MCF7, SW480, HepG2, and SGC7901 cell lines in vitro. As a result, compounds 6 and 7 showed significant activity (IC50 2.94-12.2 µM) against all tested cell lines. Structure-activity relationships of these compounds were investigated and the preliminary conclusions were provided. Moreover, a new transformation pathway was discovered in the acid hydrolysis of timosaponin B III for the first time.


Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Saponinas/química , Anemarrhena/química , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Hidrólise , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray , Esteroides/química , Relação Estrutura-Atividade
11.
Eur J Obstet Gynecol Reprod Biol ; 229: 179-184, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30205314

RESUMO

OBJECTIVE: To investigate the feasibility of proximal tubal occlusion with fibered platinum coils in subfertile women with hydrosalpinx, and to observe the clinical outcomes of subsequent treatment with in vitro fertilization and embryo transfer (IVF-ET). STUDY DESIGN: A prospective study was carried out in a university-affiliated teaching hospital. 56 women with uni- or bilateral hydrosalpinx received fibered platinum coil placement before IVF-ET. The clinical pregnancy rate and live birth rate was evaluated. Data analysis was performed with SPSS version 22.0 (SPSS, Inc., Chicago, IL, USA), using two-sided test, and a p value < 0.05 was considered statistically significant. The study has been registered in the ClinicalTrials. gov with the number of NCT03395301. RESULT(S): Successful placement was achieved in 106 fallopian tubes of 55 patients. The fibered platinum coils induced complete proximal occlusion in 52 out of 55 patients in the following 3-month HSG examination. In the 52 patients, 44 patients received following IVF-ET. The clinical pregnancy rate reached 60.5%(23/38)and live birth rate reached 60.87% (14/23) in patients less than 40 years old. CONCLUSION(S): Fibered platinum coil is a new, safe and valuable device for hysteroscopic tubal proximal occlusion in subfertile women with hydrosalpinx but with laparoscopic contradictions to improve the reproductive outcomes of IVF-ET. Capsule: Fibered platinum coil is a new, safe and valuable device for hysteroscopic tubal proximal occlusion in subfertile women with hydrosalpinx to improve the reproductive outcomes of in vitro fertilization and embryo transfer.


Assuntos
Doenças das Tubas Uterinas/cirurgia , Fertilização in vitro/estatística & dados numéricos , Procedimentos Cirúrgicos em Ginecologia/instrumentação , Adulto , Doenças das Tubas Uterinas/complicações , Feminino , Humanos , Infertilidade Feminina/etiologia , Gravidez , Taxa de Gravidez , Estudos Prospectivos
12.
Chem Biodivers ; 15(4): e1800019, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29451710

RESUMO

Using various chromatographic methods, a new hexacyclic triterpenoid, 2ß,3ß,24ß-trihydroxy-12,13-cyclotaraxer-l4-en-28oic acid (1), together with ten known compounds, 2α,3α,23-trihydroxyurs-12,20(30)-dien-28oic acid (2), 6,7-dehydroroyleanone (3), horminone (4), 7-O-methylhorminone (5), sugiol (6), demethylcryptojaponol (7), 14-deoxycoleon U (8), 5,6-didehydro-7-hydroxy-taxodone (9), ferruginol (10), and dichroanone (11), were isolated from the roots of Salvia deserta. Their structures were identified on the basis of spectroscopic analysis and comparison with the reported data. The individual compounds (1, 3 - 8) were screened for cytotoxic activity, using the sulforhodamine B bioassay (SRB) method. As the results, Compounds 3, 5, and 8 showed cytotoxic potency against A549, MDA-MB-231, KB, KB-VIN, and MCF7 cell lines with IC50 values ranging from 6.5 to 10.2 µm.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Raízes de Plantas/química , Salvia/química , Terpenos/farmacologia , Triterpenos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células MCF-7 , Estrutura Molecular , Relação Estrutura-Atividade , Terpenos/química , Terpenos/isolamento & purificação , Triterpenos/química , Triterpenos/isolamento & purificação
13.
Chin J Nat Med ; 15(3): 220-224, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28411690

RESUMO

Two new steroidal saponins, named timosaponin P (1) and timosaponin Q (2), were isolated from the rhizome parts of Anemarrhena asphodeloides Bunge using various chromatographic methods. Their structures and absolute configurations were elucidated by a combination of spectroscopic and spectrometric data, including 1D, 2D NMR, HR-ESI-MS and ECD calculations, and this is the first time the absolute configuration of C-23 of steroidal saponin was confirmed by ECD calculations.


Assuntos
Anemarrhena/química , Medicamentos de Ervas Chinesas/química , Saponinas/química , Esteroides/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Saponinas/isolamento & purificação , Esteroides/isolamento & purificação
14.
Nat Prod Res ; 31(21): 2505-2512, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28415854

RESUMO

Two new phenolic acids, ethyl pro-lithospermate (1), n-butyl pro-lithospermate (2) were isolated from Salvia yunnanensis C.H.Wright, along with nineteen known compounds (3-21). The structures of the isolated compounds were elucidated on the basis of extensive spectrometry and by comparing their physical and spectroscopic data to the literature. Among them, compounds 11, 12 and 14-16 were firstly isolated from S. yunnanensis C.H.Wright. Some of the isolated compounds were evaluated for their neuroprotection. Compounds 10-12 showed significant neuroprotective effects in PC12 cells and compounds 1, 4-7 displayed moderate neuroprotective effects.


Assuntos
Hidroxibenzoatos/química , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Salvia/química , Animais , Avaliação Pré-Clínica de Medicamentos/métodos , Peróxido de Hidrogênio/toxicidade , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Células PC12 , Extratos Vegetais/química , Ratos , Espectrometria de Massas por Ionização por Electrospray
15.
Eur J Pharmacol ; 788: 104-112, 2016 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-27318324

RESUMO

Our group synthesized propane-2-sulfonic acid octadec-9-enyl-amide (N15), a novel peroxisome proliferator activated receptor alpha (PPARα) agonist. Because PPARα activation is associated with inflammation control, we hypothesize that N15 may have anti-inflammatory effects. We investigated the effect of N15 on the regulation of inflammation in THP-1 cells stimulated with lipopolysaccharide (LPS). In particular, we assessed the production of chemokines, adhesion molecules and proinflammatory cytokines, three important types of cytokines that are released from monocytes and are involved in the development of atherosclerosis. The results showed that N15 remarkably reduced the mRNA expression of chemokines, such as monocyte chemotactic protein 1 (MCP-1 or CCL2), interleukin-8 (IL-8) and interferon-inducible protein-10 (IP-10 or CXCL10), and proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6). N15 also decreased the protein expression of vascular cell adhesion molecule (VCAM) and matrix metalloproteinase (MMP) 2 and 9. The reduction in the expression of cytokine mRNAs observed following N15 treatment was abrogated in THP-1 cells treated with PPARα siRNA, indicating that the anti-inflammatory effects of N15 are dependent on PPARα activation. Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) inhibition, which are dependent on PPARα activation, were also involved in the mechanism underlying the anti-inflammatory effects of N15. In conclusion, the novel PPARα agonist, N15, exerts notable anti-inflammatory effects, which are mediated via PPARα activation and TLR4/NF-κB and STAT3 inhibition, in LPS-stimulated THP-1 cells. In our study, N15 exhibits promise for the treatment of atherosclerosis.


Assuntos
Anti-Inflamatórios/farmacologia , PPAR alfa/agonistas , Ácidos Sulfônicos/farmacologia , Anti-Inflamatórios/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Quimiocinas/metabolismo , Fenofibrato/farmacologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Lipopolissacarídeos/farmacologia , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/biossíntese , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , NF-kappa B/metabolismo , PPAR alfa/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ácidos Sulfônicos/uso terapêutico , Receptor 4 Toll-Like/metabolismo , Molécula 1 de Adesão de Célula Vascular/biossíntese
16.
Xenobiotica ; 46(9): 816-24, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26750665

RESUMO

1. In this study, we report that gambogic acid (GA), a promising anticancer agent, potentiates clopidogrel-induced apoptosis and attenuates CPT-11-induced apoptosis by down-regulating human carboxylesterase (CES) 1 and -2 via ERK and p38 MAPK pathway activation, which provides a molecular explanation linking the effect of drug combination directly to the decreased capacity of hydrolytic biotransformation. 2. The expression levels of CES1 and CES2 decreased significantly in a concentration- and time-dependent manner in response to GA in Huh7 and HepG2 cells; hydrolytic activity was also reduced. 3. The results showed that pretreatment with GA potentiated clopidogrel-induced apoptosis by down-regulating CES1. Moreover, the GA-mediated repression of CES2 attenuated CPT-11-induced apoptosis. 4. Furthermore, the ERK and p38 MAPK pathways were involved in the GA-mediated down-regulation of CES1 and CES2. 5. Taken together, our data suggest that GA is a potent repressor of CES1 and CES2 and that combination with GA will affect the metabolism of drugs containing ester bonds.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carboxilesterase/metabolismo , Ticlopidina/análogos & derivados , Xantonas/farmacologia , Biotransformação , Camptotecina/análogos & derivados , Camptotecina/toxicidade , Clopidogrel , Regulação para Baixo , Irinotecano , Ticlopidina/farmacologia
17.
Zhongguo Zhong Yao Za Zhi ; 41(6): 976-988, 2016 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-28875658

RESUMO

The genus Solanum which is the largest genus in Solanaceae consists of more than 2 000 species, most of them are distributed in tropics and subtropics areas, and only a small amount in temperate regions throughout the world. Steroidal saponins could be found in many species of the Solanum, and they are an important group of natural products exhbiting a number of potent beneficent properties, such as anti-tumor, antibacterial, antifungal, anti-inflammatory, antiviral, antioxidant, hypoglycemic, and antihyperlipidemic effects. As supplement, this paper gives a review of different structural categories of steroidal saponins and their pharmacological effects from the solanum plants over the past decade, and it is intended to provide a point of reference for further research on steroidal saponins in Solanum plants.


Assuntos
Medicamentos de Ervas Chinesas/química , Saponinas/química , Solanum/química , Esteroides/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Saponinas/farmacologia , Esteroides/farmacologia
18.
Mol Carcinog ; 55(5): 440-57, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-25683703

RESUMO

We recently establish that aspafilioside B, a steroidal saponin extracted from Asparagus filicinus, is an active cytotoxic component. However, its antitumor activity is till unknown. In this study, the anticancer effect of aspafilioside B against HCC cells and the underlying mechanisms were investigated. Our results showed that aspafilioside B inhibited the growth and proliferation of HCC cell lines. Further study revealed that aspafilioside B could significantly induce G2 phase cell cycle arrest and apoptosis, accompanying the accumulation of reactive oxygen species (ROS), but blocking ROS generation with N-acetyl-l-cysteine (NAC) could not prevent G2/M arrest and apoptosis. Additionally, treatment with aspafilioside B induced phosphorylation of extracellular signal-regulated kinase (ERK) and p38 MAP kinase. Moreover, both ERK inhibitor PD98059 and p38 inhibitor SB203580 almost abolished the G2/M phase arrest and apoptosis induced by aspafilioside B, and reversed the expression of cell cycle- and apoptosis-related proteins. We also found that aspafilioside B treatment increased both Ras and Raf activation, and transfection of cells with H-Ras and N-Ras shRNA almost attenuated aspafilioside B-induced G2 phase arrest and apoptosis as well as the ERK and p38 activation. Finally, in vivo, aspafilioside B suppressed tumor growth in mouse xenograft models, and the mechanism was the same as in vitro study. Collectively, these findings indicated that aspafilioside B may up-regulate H-Ras and N-Ras, causing c-Raf phosphorylation, and lead to ERK and p38 activation, which consequently induced the G2 phase arrest and apoptosis. This study provides the evidence that aspafilioside B is a promising therapeutic agent against HCC.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Saponinas/administração & dosagem , Espirostanos/administração & dosagem , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Genes ras/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Saponinas/farmacologia , Espirostanos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Zhonghua Nan Ke Xue ; 21(8): 713-6, 2015 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-26442298

RESUMO

OBJECTIVE: To assess the association of the A260G and A386G single nucleotide polymorphisms (SNP) of the DAZL gene with male infertility in the Chinese population of Zhejiang Province. METHODS: We collected the peripheral blood samples from 317 idiopathic infertile males with azoospermia or oligozoospermia and 246 normal fertile men, and genotyped the polymorphic loci of the A260G and A386G polymorphisms of the DAZL gene using the SNaPshot technique. RESULTS: The DAZL gene A260G was found genetically polymorphic in the Chinese population of Zhejiang Province, with the gene frequencies and their distribution consistent to the Hardy-Weinberg equilibrium. The frequencies of the AA, AG and GG genotypes of the A260G polymorphism were 92.3%, 7.3%, and 0.4% respectively in the normal controls and 94.3%, 5.7%, and 0% in the infertile patients, with no statistically significant differences between the two groups (P = 0.43, OR = 0.78, 95% CI 0.413-1.46). Heterozygosis (AG) of A386G was found in 1 of the control males but not in the infertile patients, while homozygosis (GG) of A386G was not observed in either group (P = 0.259, OR = 0.698, 59% CI: 0.374-1.306). CONCLUSION: A260G and A386G SNPs of the DAZL gene are not associated with spermatogenic failure and neither represents a molecular marker for the genetic diagnosis of male infertility in the Chinese population of Zhejiang Province.


Assuntos
Infertilidade Masculina/genética , Polimorfismo de Nucleotídeo Único , Proteínas de Ligação a RNA/genética , Povo Asiático , Azoospermia/genética , China , Frequência do Gene , Marcadores Genéticos , Genótipo , Humanos , Masculino , Oligospermia/genética , Polimorfismo Genético
20.
Zhonghua Nan Ke Xue ; 21(12): 1082-6, 2015 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-26817299

RESUMO

OBJECTIVE: To investigate the association of male reproductive tract infection (RTI) with semen parameters and sperm DNA damage. METHODS: We classified 1 084 males attending the infertility clinic into an RTI group (n = 300) and a non-RTI control group (n = 784). According to the WHO standards, we obtained routine semen parameters, detected sperm morphology, and determined the sperm DNA fragmentation index (DFI) by sperm chromatin structure assay. RESULTS: There were statistically significant differences between the RTI and control groups in the semen volume ( [2.58 ± 1.20] vs [3.00 ± 2.10] ml), grade a + b sperm ([50.6 ± 17.2] vs [53.2 ± 15.8]%), grade d sperm ( [39. 8 ± 17.8] vs [36.5 ± 16.2]%), and total sperm count ([218.5 ± 185.0 ] vs [278.5 ± 375.5 ] x 10(6)/ejaculate) (all P < 0.05), but not in the males' age, sperm concentration or pH value (P > 0.05). The percentage of morphologically normal sperm was significantly lower ([3.46 ± 2.90] vs [4.61 ± 3.60%, P < 0.05) but the DFI was markedly higher in the RTI group than in the control ([19.4 ± 11.4] vs [15.2 ± 8.8]% , P < 0.01). The percentage of the cases with DFI > 30% was remarkably higher (13.0 vs 5.74% ) while that of the cases with DFI < 10% dramatically lower in the former than in the latter (16.0 vs 28.0%). The level of seminal plasma elastase was correlated negatively to sperm concentration, sperm count, and the percentage of morphologically normal sperm (P < 0.05) but positively to DFI and grade d sperm (P < 0.05 or P < 0.01). CONCLUSION: Male reproductive tract infection not only affects semen parameters and sperm morphology but also causes serious sperm DNA damage.


Assuntos
Infertilidade Masculina/fisiopatologia , Infecções do Sistema Genital/fisiopatologia , Análise do Sêmen , Fragmentação do DNA , Humanos , Masculino , Sêmen/química , Contagem de Espermatozoides , Espermatozoides/patologia
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