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1.
Cell Regen ; 11(1): 36, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36316503

RESUMO

Malignant glioma is a highly heterogeneous and invasive primary brain tumor characterized by high recurrence rates, resistance to combined therapy, and dismal prognosis. Glioma stem cells (GSCs) are likely responsible for tumor progression, resistance to therapy, recurrence, and poor prognosis owing to their high self-renewal and tumorigenic potential. As a family member of BMP signaling, bone morphogenetic protein4 (BMP4) has been reported to induce the differentiation of GSCs and neural stem cells (NSCs). However, the molecular mechanisms underlying the BMP4-mediated effects in these two cell types are unclear. In this study, we treated hGSCs and hNSCs with BMP4 and compared the phenotypic and transcriptional changes between these two cell types. Phenotypically, we found that the growth of hGSCs was greatly inhibited by BMP4, but the same treatment only increased the cell size of hNSCs. While the RNA sequencing results showed that BMP4 treatment evoked significantly transcriptional changes in both hGSCs and hNSCs, the profiles of differentially expressed genes were distinct between the two groups. A gene set that specifically targeted the proliferation and differentiation of hGSCs but not hNSCs was enriched and then validated in hGSC culture. Our results suggested that hGSCs and hNSCs responded differently to BMP4 stimulation. Understanding and investigating different responses between hGSCs and hNSCs will benefit finding partner factors working together with BMP4 to further suppress GSCs proliferation and stemness without disturbing NSCs.

2.
Cell Regen ; 11(1): 23, 2022 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-35778531

RESUMO

Malignant Glioma is characterized by strong self-renewal potential and immature differentiation potential. The main reason is that malignant glioma holds key cluster cells, glioma stem cells (GSCs). GSCs contribute to tumorigenesis, tumor progression, recurrence, and treatment resistance. Interferon-beta (IFN-ß) is well known for its anti-proliferative efficacy in diverse cancers. IFN-ß also displayed potent antitumor effects in malignant glioma. IFN-ß affect both GSCs and Neural stem cells (NSCs) in the treatment of gliomas. However, the functional comparison, similar or different effects of IFN-ß on GSCs and NSCs are rarely reported. Here, we studied the similarities and differences of the responses to IFN-ß between human GSCs and normal NSCs. We found that IFN-ß preferentially inhibited GSCs over NSCs. The cell body and nucleus size of GSCs increased after IFN-ß treatment, and the genomic analysis revealed the enrichment of the upregulated immune response, cell adhesion genes and down regulated cell cycle, ribosome pathways. Several typical cyclin genes, including cyclin A2 (CCNA2), cyclin B1 (CCNB1), cyclin B2 (CCNB2), and cyclin D1 (CCND1), were significantly downregulated in GSCs after IFN-ß stimulation. We also found that continuous IFN-ß stimulation after passage further enhanced the inhibitory effect. Our study revealed how genetic diversity resulted in differential effects in response to IFN-ß treatment. These results may contribute to improve the applications of IFN-ß in anti-cancer immunotherapy. In addition, these results may also help to design more effective pharmacological strategies to target cancer stem cells while protecting normal neural stem cells.

3.
Front Chem ; 10: 922110, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35734442

RESUMO

Janus kinases (JAKs) play a key role in subtly regulating proliferation, apoptosis, and differentiation of cancer cells, and their inhibitors are actively sought as new drug leads. By developing JAKs based affinity ultrafiltration method coupled with LC/Q-TOF-MS in order to discover selective JAKs inhibitors from total quaternary alkaloids (QAs) from Zanthoxylum simulans, peak 19 (Berberine) and peak 21 (Chelerythrine) were revealed to exhibit notable selectivity on JAK1, JAK2, and JAK3 over Tyk2. In addition, Chelerythrine showed stronger inhibitory activity than the positive control (Cerdulatinib) on gastric cancer cells (AGS), while Berberine, with weaker inhibition. Chelerythrine and Berberine also showed obvious inhibition on human hepatocyte cells (LO2). Furthermore, molecular docking analysis revealed their discrepancies due to different interaction bonds and characteristic residues. Quaternary N was proposed as the functional group to enhance the selectivity of JAK1, and some specific moieties towards Asp1021, Leu855, and Leu828 were suggested to increase the selectivity for JAK1, JAK2, and JAK3, respectively. As the most potential inhibitor of JAKs from QAs, Chelerythrine exhibited distinct suppression of adhesion, migration, invasion, and stimulating apoptosis of AGS cells, which was consistent with the significant down-regulation of estrogen receptors (ER-α36, ER-α66, and ER-ß1) and Src expression. In conclusion, an efficient screening approach was developed to identify Berberine and Chelerythrine as potential selective candidates from Zanthoxylum simulans with significant anti-proliferative activity against gastric carcinoma. As we know, it was the first report to propose an estrogen signal pathway for Chelerythrine in anti-gastric cancer cells (AGS) study. The results supported Chelerythrine inhibitory effects on AGS by not only direct inhibiting JAKs but also down-regulating the estrogen pathway.

4.
Anticancer Res ; 42(2): 845-855, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35093882

RESUMO

BACKGROUND/AIM: The poor prognosis and chemoresistance of patients with triple-negative breast cancer (TNBC) urge the development of new therapeutic strategies. Snail mucus has shown its ability against inflammation, a process closely related to tumorigenesis, suggesting a potential anti-cancer activity. MATERIALS AND METHODS: The effect and mechanisms of snail mucus on cell viability were determined by IncuCyte Live-cell analysis and molecular biological methods. The anti-cancer fractions of snail mucus were isolated and identified by medium pressure liquid chromatography (MPLC) and nuclear magnetic resonance (NMR) spectrometry analysis. RESULTS: Snail mucus significantly decreased the viability of TNBC cells with relatively lower cytotoxicity to normal breast epithelial cells and enhanced their response to chemotherapy through activation of Fas signaling by suppressing nucleolin. Two peptide fractions have been identified as the anti-cancer ingredients of the snail mucus. CONCLUSION: Snail mucus can induce programmed cell death via the extrinsic apoptotic pathway and has therapeutic potential by achieving a chemo-sensitizing effect in TNBCs.


Assuntos
Antineoplásicos/farmacologia , Muco , Transdução de Sinais/efeitos dos fármacos , Caramujos , Neoplasias de Mama Triplo Negativas/metabolismo , Receptor fas/metabolismo , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Muco/química , Muco/metabolismo , Caramujos/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia
5.
Mol Ther Nucleic Acids ; 25: 536-553, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34589276

RESUMO

Mutant p53 (mutp53) commonly loses its DNA binding affinity to p53 response elements (p53REs) and fails to induce apoptosis fully. However, the p53 mutation does not predict chemoresistance in all subtypes of breast cancers, and the critical determinants remain to be identified. In this study, mutp53 was found to mediate chemotherapy-induced long intergenic noncoding RNA-p21 (lincRNA-p21) expression by targeting the G-quadruplex structure rather than the p53RE on its promoter to promote chemosensitivity. However, estrogen receptor alpha (ERα) suppressed mutp53-mediated lincRNA-p21 expression by hijacking mutp53 to upregulate damaged DNA binding protein 2 (DDB2) transcription for subsequent DNA repair and chemoresistance. Levels of lincRNA-p21 positively correlated with the clinical responses of breast cancer patients to neoadjuvant chemotherapy and had an inverse correlation with the ER status and DDB2 level. In contrast, the carboplatin-induced DDB2 expression was higher in ER-positive breast tumor tissues. These results demonstrated that ER status determines the oncogenic function of mutp53 in chemoresistance by switching its target gene preference from lincRNA-p21 to DDB2 and suggest that induction of lincRNA-p21 and targeting DDB2 would be effective strategies to increase the chemosensitivity of mutp53 breast cancer patients.

6.
Nutrients ; 13(8)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34444960

RESUMO

Hesperidin (HD) is a common flavanone glycoside isolated from citrus fruits and possesses great potential for cardiovascular protection. Hesperetin (HT) is an aglycone metabolite of HD with high bioavailability. Through the docking simulation, HD and HT have shown their potential to bind to two cellular proteins: transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2), which are required for the cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our results further found that HT and HD suppressed the infection of VeroE6 cells using lentiviral-based pseudo-particles with wild types and variants of SARS-CoV-2 with spike (S) proteins, by blocking the interaction between the S protein and cellular receptor ACE2 and reducing ACE2 and TMPRSS2 expression. In summary, hesperidin is a potential TMPRSS2 inhibitor for the reduction of the SARS-CoV-2 infection.


Assuntos
Tratamento Farmacológico da COVID-19 , Hesperidina/química , Hesperidina/farmacologia , SARS-CoV-2/efeitos dos fármacos , Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , COVID-19/metabolismo , COVID-19/virologia , Linhagem Celular Tumoral , Chlorocebus aethiops , Proteases Semelhantes à Papaína de Coronavírus/química , Proteases Semelhantes à Papaína de Coronavírus/metabolismo , Humanos , Simulação de Acoplamento Molecular , SARS-CoV-2/metabolismo , Serina Endopeptidases/química , Serina Endopeptidases/efeitos dos fármacos , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Células Vero
7.
Front Genet ; 12: 639858, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34295351

RESUMO

Glioma is the most common and malignant primary brain tumor. Patients with malignant glioma usually have a poor prognosis due to drug resistance and disease relapse. Cancer stem cells contribute to glioma initiation, progression, resistance, and relapse. Hence, quick identification and efficient understanding of glioma stem cells (GSCs) are of profound importance for therapeutic strategies and outcomes. Ideally, therapeutic approaches will only kill cancer stem cells without harming normal neural stem cells (NSCs) that can inhibit GSCs and are often beneficial. It is key to identify the differences between cancer stem cells and normal NSCs. However, reports detailing an efficient and uniform protocol are scarce, as are comparisons between normal neural and cancer stem cells. Here, we compared different protocols and developed a fast and efficient approach to obtaining high-purity glioma stem cell by tracking observation and optimizing culture conditions. We examined the proliferative and differentiative properties confirming the identities of the GSCs with relevant markers such as Ki67, SRY-box containing gene 2, an intermediate filament protein member nestin, glial fibrillary acidic protein, and s100 calcium-binding protein (s100-beta). Finally, we identified distinct expression differences between GSCs and normal NSCs including cyclin-dependent kinase 4 and tumor protein p53. This study comprehensively describes the features of GSCs, their properties, and regulatory genes with expression differences between them and normal stem cells. Effective approaches to quickly obtaining high-quality GSCs from patients should have the potential to not only help understand the diseases and the resistances but also enable target drug screening and personalized medicine for brain tumor treatment.

8.
Oncogene ; 40(6): 1162-1175, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33335306

RESUMO

Smoker patients with non-small cell lung cancer (NSCLC) have poorer prognosis and survival than those without smoking history. However, the mechanisms underlying the low response rate of those patients to EGFR tyrosine kinase inhibitors (TKIs) are not well understood. Here we report that exposure to cigarette smoke extract enhances glycolysis and attenuates AMP-activated protein kinase (AMPK)-dependent inhibition of mTOR; this in turn reduces the sensitivity of NSCLC cells with wild-type EGFR (EGFRWT) to EGFR TKI by repressing expression of liver kinase B1 (LKB1), a master kinase of the AMPK subfamily, via CpG island methylation. In addition, LKB1 expression is correlated positively with sensitivity to TKI in patients with NSCLC. Moreover, combined treatment of EGFR TKI with AMPK activators synergistically increases EGFR TKI sensitivity. Collectively, the current study suggests that LKB1 may serve as a marker to predict EGFR TKI sensitivity in smokers with NSCLC carrying EGFRWT and that the combination of EGFR TKI and AMPK activator may be a potentially effective therapeutic strategy against NSCLC with EGFRWT.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Proteínas Serina-Treonina Quinases/genética , Serina-Treonina Quinases TOR/genética , Quinases Proteína-Quinases Ativadas por AMP , Animais , Carcinoma Pulmonar de Células não Pequenas/induzido quimicamente , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Fumar Cigarros/efeitos adversos , Ilhas de CpG/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/genética , Xenoenxertos , Humanos , Camundongos , Mutação/genética , Inibidores de Proteínas Quinases/farmacologia , Proteínas Quinases/genética , Transdução de Sinais/efeitos dos fármacos , Fumar/efeitos adversos
9.
Org Biomol Chem ; 18(21): 4034-4045, 2020 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-32191248

RESUMO

An efficiently divergent intramolecular Friedel-Crafts alkylation by unactivated alkenes with seleniranium ion-controlled Markovnikov/anti-Markovnikov specificities under mild conditions has been investigated. 2-Benzoxepin, isochroman, and isochromene can be produced in one-pot procedures from the same substrate in high yields and with high regio- and stereospecificity. The products are challenging to access via 7-endo-trig carbocyclizations and by 7-endo-trig carbocyclization/rearrangement/6-exo-trig oxycyclization and 6-exo-trig carbocyclization/deselenenylation reaction sequences, respectively. Mechanistic experiments indicated that in addition to the stereospecific anti-addition processes of the cyclization reactions, the formation of a stable carbocation after ring opening of the seleniranium ion leads to an NPSP-mediated 7-endo-trig carbocyclization; the steric hindrance of the seleniranium intermediate controls the regioselectivity when using TPSCA at 60 °C, which promotes 6-exo-trig carbocyclization. Two distinct catalytic cycles were proposed, and the structures of transition states and products were identified by ab initio calculations and X-ray analyses.

10.
Biomed Environ Sci ; 30(9): 671-675, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29081342

RESUMO

We assessed the role of diabetes mellitus (DM) on treatment effects in drug-susceptible initial pulmonary tuberculosis (PTB) patients. A prospective study was conducted in eight provinces of China from October 2008 to December 2010. We enrolled 1,313 confirmed drug-susceptible initial PTB patients, and all subjects received the treatment regimen (2H3R3E3Z3/4H3R3) as recommended by the national guidelines. Of the 1,313 PTB patients, 157 (11.9%) had DM; these patients had more sputum smear-positive rates at the end of the second month [adjusted odds ratios (aOR) 2.829, 95% confidence intervals (CI) 1.783-4.490], and higher treatment failure (aOR 2.120, 95% CI 1.565-3.477) and death rates (aOR 1.536, 95% CI 1.011-2.628). DM was a contributing factor for culture-positive rates at the end of the second month and treatment failure and death of PTB patients, thus playing an unfavorable role in treatment effects of PTB.


Assuntos
Antituberculosos/uso terapêutico , Diabetes Mellitus/terapia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , China/epidemiologia , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Masculino , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/epidemiologia
11.
Biomed Environ Sci ; 29(8): 612-617, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27660228

RESUMO

The objective of this prospective study of the risks of treatment failure in patients with drug-susceptible pulmonary tuberculosis (PTB) was to provide reference data to help develop a disease control strategy. Participants were recruited in eight provinces of China from October 2008 to December 2010. A total of 1447 patients with drug-susceptible PTB and older than 15 years of age were enrolled. Demographic characteristics, bacteriological test results, and patient outcome, i.e., cure or treatment failure were recorded and compared using the chi-square or Fisher's exact tests. Multivariate logistic regression was used to identify factors associated with risk of treatment failure. Of the 1447 patients who were enrolled, 1349 patients (93.2%) were successfully treated and 98 (6.8%) failed treatment. Failure was significantly associated with age 365 years [odds ratio (OR)=2.522, 95% confidence interval (CI): (1.097-5.801)], retreatment [OR=2.365, 95% CI: (1.276-4.381)], missed medicine [OR=1.836, 95% CI: (1.020-3.306)], treatment not observed [OR=1.879 95% CI: (1.105-3.195)], and positive culture result after the first [OR=1.971, 95% CI: (1.080-3.597)] and second month [OR=4.659, 95% CI: (2.590-8.382)]. The risk factors associated with treatment failure were age 365 years, retreatment, missed medication, treatment not observed, and positive culture at the end of month 1 or month 2. These risk factors should be monitored during treatment and interventions carried out to reduce or prevent treatment failure and optimize treatment success.


Assuntos
Antituberculosos/uso terapêutico , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Adulto , Idoso , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/fisiologia , Estudos Prospectivos , Retratamento , Fatores de Risco , Falha de Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia , Adulto Jovem
12.
Appl Plant Sci ; 4(3)2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27011895

RESUMO

PREMISE OF THE STUDY: Polymorphic microsatellite markers were developed to facilitate studies on the fine-scale population genetic structure of Ficus tikoua (Moraceae), a prostrate shrub known to have highly restricted gene flow. METHODS AND RESULTS: Microsatellite primers were developed using the biotin-streptavidin capture method and scanned for polymorphism within 76 individuals sampled from three natural F. tikoua populations. Fourteen loci were shown to be polymorphic, with allele numbers ranging from three to 16. The observed and expected heterozygosity in the three populations ranged from 0 to 1 and from 0 to 0.87, respectively. Substantial divergence was found among the populations at some loci. All loci can be successfully amplified in at least eight other Ficus species, indicating good transferability within the genus. CONCLUSIONS: The 14 microsatellite loci will be a helpful tool for assessing the fine-scale genetic structure of F. tikoua.

13.
Ecol Evol ; 6(2): 607-19, 2016 01.
Artigo em Inglês | MEDLINE | ID: mdl-26843943

RESUMO

Most plants are pollinated passively, but active pollination has evolved among insects that depend on ovule fertilization for larval development. Anther-to-ovule ratios (A/O ratios, a coarse indicator of pollen-to-ovule ratios) are strong indicators of pollination mode in fig trees and are consistent within most species. However, unusually high values and high variation of A/O ratios (0.096-10.0) were detected among male plants from 41 natural populations of Ficus tikoua in China. Higher proportions of male (staminate) flowers were associated with a change in their distribution within the figs, from circum-ostiolar to scattered. Plants bearing figs with ostiolar or scattered male flowers were geographically separated, with scattered male flowers found mainly on the Yungui Plateau in the southwest of our sample area. The A/O ratios of most F. tikoua figs were indicative of passive pollination, but its Ceratosolen fig wasp pollinator actively loads pollen into its pollen pockets. Additional pollen was also carried on their body surface and pollinators emerging from scattered-flower figs had more surface pollen. Large amounts of pollen grains on the insects' body surface are usually indicative of a passive pollinator. This is the first recorded case of an actively pollinated Ficus species producing large amounts of pollen. Overall high A/O ratios, particularly in some populations, in combination with actively pollinating pollinators, may reflect a response by the plant to insufficient quantities of pollen transported in the wasps' pollen pockets, together with geographic variation in this pollen limitation. This suggests an unstable scenario that could lead to eventual loss of wasp active pollination behavior.

14.
Zhong Yao Cai ; 38(4): 786-9, 2015 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-26672348

RESUMO

OBJECTIVE: To investigate the effects of Cordycepin on proliferation and apoptosis of A549 cells, and its possible mechanism of action. METHODS: Human lung cancer cell line A549 cells were treated with different concentrations of Cordycepin for 24 h. MTS assay was used to detect cell proliferation. Hoechst 33258 staining and Annexin V/PI flow cytometry were used to determine the apoptosis of A549 cells. The protein expression of nuclear factor-κB p65 (NF-κB p65), BAX, BCL-2 and cleaved Caspase-3 was determined by Western blot. RESULTS: In a dose dependent way, Cordycepin inhibited the proliferation and promoted the apoptosis of A549 cells, increased the expression of BAX and cleaved Caspase-3, while decreased the expression of BCL-2. The Western blot results showed, Cordycepin dose-dependently inhibited the entry of NF-κB p65 to nuclear in A59 cells. CONCLUSION: Cordycepin can inhibit the proliferation and induct the apoptosis of A549 cells, the mechanism of action is achieved by inhibiting the NF-κB pathway.


Assuntos
Desoxiadenosinas/farmacologia , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Apoptose , Caspase 3/metabolismo , Linhagem Celular Tumoral/efeitos dos fármacos , Proliferação de Células , Humanos , Neoplasias Pulmonares/metabolismo
15.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-464588

RESUMO

Objective To establish a method to detect the content of propylene glycol in the recombinant human glucagon-like peptide-1(rhGLP-1)(7-36) injection by gas chromatography(GC). Methods GC was performed using a quartz capillary column (30 m ×320 μm,0.5 μm) with the mobile phase of N2 and inlet temperature of 230℃ at the flow rate of 1ml/min and column temperature of 250 ℃, the injection volume was 1μl. Results The calibration curve was linear within the range of 0.5-1.5 mg/ml, r=0.9991. The average recovery rate was 100.2%; under different chromatographic conditions, the method had good stability, RSD was less than 2.0%. Conclusion This method is simple, accurate and reproducible, and can be applied in the determination of propylene glycol content in rhGLP-1(7-36) injection.

16.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-845684

RESUMO

Objective: To establish a method to detect the content of propylene glycol in the recombinant human glucagon-like peptide-1 (rhGLP-1) (7-36) injection by gas chromatography (GC). Methods: GC was performed using a quartz capillary column (30 m×320 μm,0.5 μm) with the mobile phase of N2 and inlet temperature of 230℃ at the flow rate of 1ml/min and column temperature of 250 ℃, the injection volume was 1μl. Results: The calibration curve was linear within the range of 0.5-1.5 mg/ml, r=0.9991. The average recovery rate was 100.2%; under different chromatographic conditions, the method had good stability, RSD was less than 2.0%. Conclusion: This method is simple, accurate and reproducible, and can be applied in the determination of propylene glycol content in rhGLP-1 (7-36) injection.

17.
Stroke ; 45(6): 1739-47, 2014 06.
Artigo em Inglês | MEDLINE | ID: mdl-24763930

RESUMO

BACKGROUND AND PURPOSE: In Rivaroxaban Once Daily Oral Direct Factor Xa Inhibitor Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial, rivaroxaban was noninferior to dose-adjusted warfarin in preventing stroke or systemic embolism among patients with nonvalvular atrial fibrillation at moderate to high stroke risk. Because of differences in patient demographics, epidemiology, and stroke risk management in East Asia, outcomes and relative effects of rivaroxaban versus warfarin were assessed to determine consistency among East Asians versus other ROCKET AF participants. METHODS: Baseline demographics and interaction of treatment effects of rivaroxaban and warfarin among patients within East Asia and outside were assessed. RESULTS: A total of 932 (6.5%) ROCKET AF participants resided in East Asia. At baseline, East Asians had lower weight, creatinine clearance, and prior vitamin K antagonist use; higher prevalence of prior stroke; and less congestive heart failure and prior myocardial infarction than other participants. Despite higher absolute event rates for efficacy and safety outcomes in East Asians, the relative efficacy of rivaroxaban (20 mg once daily; 15 mg once daily for creatinine clearance of 30-49 mL/min) versus warfarin with respect to the primary efficacy end point (stroke/systemic embolism) was consistent among East Asians and non-East Asians (interaction P=0.666). Relative event rates for the major or nonmajor clinically relevant bleeding in patients treated with rivaroxaban and warfarin were consistent among East Asians and non-East Asians (interaction P=0.867). CONCLUSIONS: Observed relative efficacy and safety of rivaroxaban versus warfarin were similar among patients within and outside East Asia. Rivaroxaban, 20 mg once daily, is an alternative to warfarin for stroke prevention in East Asians with nonvalvular atrial fibrillation.


Assuntos
Anticoagulantes/administração & dosagem , Povo Asiático , Morfolinas/administração & dosagem , Acidente Vascular Cerebral/prevenção & controle , Tiofenos/administração & dosagem , Idoso , Anticoagulantes/efeitos adversos , Método Duplo-Cego , Inibidores do Fator Xa , Ásia Oriental/epidemiologia , Feminino , Humanos , Masculino , Morfolinas/efeitos adversos , Fatores de Risco , Rivaroxabana , Acidente Vascular Cerebral/epidemiologia , Tiofenos/efeitos adversos , Vitamina K/antagonistas & inibidores , Varfarina/administração & dosagem , Varfarina/efeitos adversos
18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-287466

RESUMO

<p><b>OBJECTIVE</b>To explore the effect of Chinese herbs for Shen invigorating and blood activating (CHSIBA) on the number of endothelial progenitor cells (EPCs) in the bone marrow and the peripheral blood and the signaling pathway of bone marrow matrix metalloproteinase 9 (MMP-9) of the myocardial infarction (MI) model rats.</p><p><b>METHODS</b>The MI rat model was established by ligation. Thirty successfully modeled rats were randomly divided into the high dose CHSIBA group, the low dose CHSIBA group, and the model group, 10 in each group. Besides, another 10 normal rats were recruited as the blank group. Rats in the high dose CHSIBA group and the low dose CHSIBA group were administered with CHSIBA at 3 g/kg and 1.5 g/kg body weight by gastrogavage (by adding them in 4 mL physiological saline), once daily. Rats in the model group and the blank group were administered with 4 mL physiological saline once daily. The EPCs were collected from the bone marrow and the peripheral blood 4 weeks later. Seven days later the CD34/CD133 phenotype was identified in collected sticking wall cells using flow cytometry. The MMP-9 and water soluble Kit ligand (sKitL) were detected using Western blot. The expressions of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1alpha (SDF-1alpha) were detected using ELISA.</p><p><b>RESULTS</b>The CD34/CD133 positive rate and the EPC quantity in the bone marrow and the peripheral blood were higher in the high dose CHSIBA group and the low dose CHSIBA group than in the model group (P < 0.05, P < 0.01). Besides, the expressions of VEGF, SDF-1alpha, MMP-9, and sKitL in the bone marrow and the peripheral blood were also higher in the high dose CHSIBA group and the low dose CHSIBA group than in the model group (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>CHSIBA could activate MMP-9 signaling pathway, increase its upstream and downstream signal expression levels, and mobilize EPCs in the bone marrow to enter the blood circulation.</p>


Assuntos
Animais , Masculino , Ratos , Células da Medula Óssea , Metabolismo , Medicamentos de Ervas Chinesas , Farmacologia , Células Endoteliais , Metabolismo , Metaloproteinase 9 da Matriz , Metabolismo , Infarto do Miocárdio , Metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Células-Tronco , Metabolismo
19.
Molecules ; 17(10): 12140-50, 2012 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-23085661

RESUMO

In order to develop efficient lures for soybean pod borer Leguminivora glycinivorella (Matsumura) in China, (E,E)-8,10-dodecadienyl acetate (EE-8,10-12:Ac), the main component of the pheromone of L. glycinivorella, and 12 structurally-related compounds were synthesised in good overall yields, regiospecificities, and stereo-selectivities via coupling reactions catalysed by Li2CuCl4. The effect of different synthetic compounds, alone or in combination with EE-8,10-12:Ac, on numbers of captured L. glycinivorella males was evaluated. EE-8,10-12:Ac, (E)-10-dodecenyl acetate (E-10-12:Ac), (E)-8-dodecenol (E-8-12:OH), tetradecyl acetate (14:Ac), and (Z)-9-tetradecenyl acetate (Z-9-14:Ac) alone displayed different attractiveness to L. glycinivorella males. 14:Ac, E-8-12:OH, E-10-12:Ac, (E,E)-8,10-dodecadienal (EE-8,10-12:Ald), (E)-8-dodecenal (E-8-12:Ald), (E)-10-dodecenal (E-10-12:Ald) and Z-9-14:Ac all showed a synergistic effect to EE-8,10-12:Ac at certain dosages. The binary mixtures of EE-8,10-12:Ac and E-10-12:Ald, Z-9-14:Ac,14:Ac, E-8-12:Ald, EE-8,10-12:Ald, E-8-12:OH, or E-10-12:Ac in suitable ratios give 17.00-, 10.98-, 10.67-, 6.73-, 5.54-, 4.30- and 4.50-fold increases in trap catch, respectively, over the standard pheromone lure, and as novel pheromone blends, demonstrated potential use in pheromone traps to monitor or control L. glycinivorella populations in China.


Assuntos
Mariposas/fisiologia , Atrativos Sexuais/síntese química , Animais , Masculino , Atrativos Sexuais/fisiologia , Comportamento Sexual Animal
20.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-289698

RESUMO

<p><b>OBJECTIVE</b>To examine the effect of a Chinese medicinal herbal formula (Feitai Capsule, ) on the quality of life (QOL) and progression-free survival (PFS) of patients with unresectable non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Sixty-two patients were randomly divided into the treatment group (31 cases) and the control group (31 cases). For the treatment group, 4 capsules (1.2 g/capsule) of Feitai Capsule were administered 3 times a day after meals for 3 weeks; then no drug was administered for 1 week. This schedule was continued for at least 3 more cycles (12 weeks totally). If there were no obvious toxic reactions, the treatment was extended. The patients were evaluated at least once every 8 weeks until progressive disease (PD). For the control group, the regular follow-up and evaluation were performed at least once every 8 weeks until PD. Clinical symptoms, objective response, physical constitution and energy, QOL, and PFS were evaluated regularly. Analysis of variance (ANOVA), a non-parametric test, and analysis of covariance were used to compare clinical features, amelioration of clinical symptoms, physical constitution and energy, and QOL. Kaplan-Meier analysis was used to compare the two-group PFS.</p><p><b>RESULTS</b>Sixty patients finished the final evaluation, with 30 patients in each group. Baseline characters between groups were not significantly different (P>0.05). The control group had a 36.7% improvement in clinical symptoms, while the treatment group had a 73.3% improvement. This difference was statistically significant (Z= -2.632, P=0.008). The control group had a 26.7% improvement in the Karnofsky performance status (KPS), while the treatment group had a 53.4% improvement. This was also significantly different (Z=-2.182, P=0.029). A comparative analysis indicated a positive correlation (r=0.917, P<0.001). Compared with the control group, QOL in the treatment group was significantly improved, except in the social/family condition and doctor-patient relationship indicators. The PFS of the treatment group and control group were 6.23 months and 4.67 months, respectively (P=0.048).</p><p><b>CONCLUSION</b>Feitai Capsule, a Chinese medicinal herbal treatment could improve the QOL and extend the PFS of the unresectable NSCLC patients.</p>


Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cápsulas , Carcinoma Pulmonar de Células não Pequenas , Tratamento Farmacológico , Cirurgia Geral , Estudos de Casos e Controles , Intervalo Livre de Doença , Medicamentos de Ervas Chinesas , Usos Terapêuticos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares , Tratamento Farmacológico , Cirurgia Geral , Qualidade de Vida
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