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1.
iScience ; 19: 662-675, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31472341

RESUMO

Graphdiyne (GDY) as an emerging 2D carbon-network nanomaterial possesses many fascinating properties that lead to numerous exciting applications, but the use of GDY and its derivatives in the antibacterial field has not yet been discovered. In this study, we first report on the use and evaluation of GDY and graphdiyne oxide (GDYO) as antibacterial agents and propose the antibacterial mechanisms of GDY-based nanomaterials. GDYO has been synthesized via the surface oxidation of GDY, and the antibacterial activity of GDYO has been compared with that of GDY through a series of antibacterial tests. Surprisingly, surface oxidation endowed inert GDY with superior antibacterial capability against two representative bacterial models: Escherichia coli and Staphylococcus aureus. Antibacterial mechanism experiments disclose that the antibacterial function of GDYO is a result of reactive oxygen species-dependent oxidation stress when a dispersed GDYO suspension has a direct contact with bacteria especially under visible light irradiation.

2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1344-1347, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418405

RESUMO

Abstract  Numerous studies have confirmed that abnormal activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway is one of the most common induction mechanisms of T-ALL. In recent years, many literature report that multiple abnormally expressed microRNAs (miRNAs) can participate in the development of T-ALL by regulating the PI3K/AKT signaling pathway. For example, overexpression of miR-19 and miR181a can activate the PI3K/AKT signaling pathway, which leads to the development of T-ALL and induction of chemotherapy drug resistance, as well as the low expression of miR-26b and miR-29a. Apart from the inhibitors and traditional Chinese medicines that target the PI3K/AKT signaling pathway, regulation of the expression of the corresponding miRNA may also be a potential treatment protocol for T-ALL. The mechanisms of PI3K/AKT signaling pathway involved in the development of T-ALL, the role of miRNAs in the PI3K/AKT signaling pathway and the targeted therapy based on this signaling pathway are summarized briefly in this review.


Assuntos
Leucemia de Células T , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , MicroRNAs , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais
3.
J Infect ; 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31442461

RESUMO

OBJECTIVES: Microbiological diagnosis is essential during clinical management of focal infections. Metagenomic next generation sequencing (mNGS) has been reported as a promising diagnostic tool in infectious diseases. However, little is known about the clinical utility of mNGS in focal infections. METHODS: We conducted a single-center retrospective study to investigate impact of mNGS on focal infection diagnosis and compared it with conventional methods, including culture, pathological examination, Xpert MTB/RIF, etc. 98 suspected focal infections cases were enrolled, and medical records were reviewed to determine their rates of detection, time-to-identification, and clinical outcomes. RESULTS: mNGS showed a satisfying diagnostic positive percent agreement of 86.30% (95% CI: 75.79%-92.88%) in a variety of tissues, compared to 45.21% (95% CI: 33.68%-57.24%) for culture and 57.53% (95% CI: 45.43%-68.84%)f for conventional methods (p<0.0125), and detected an extra 34 pathogenic microorganisms. Time requirement for pathogen identification using mNGS ranges from 31 hours to 55 hours, which showed an advantage over culture. (82.36 hours; 95%CI: 65.83,98.89; P<0.05) CONCLUSIONS: mNGS showed promising potential in pathogenic diagnosis during focal infections and might enable clinicians to make more timely and targeted therapeutic decisions.

4.
Nature ; 572(7767): 56-61, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31316207

RESUMO

The radiation-based sterile insect technique (SIT) has successfully suppressed field populations of several insect pest species, but its effect on mosquito vector control has been limited. The related incompatible insect technique (IIT)-which uses sterilization caused by the maternally inherited endosymbiotic bacteria Wolbachia-is a promising alternative, but can be undermined by accidental release of females infected with the same Wolbachia strain as the released males. Here we show that combining incompatible and sterile insect techniques (IIT-SIT) enables near elimination of field populations of the world's most invasive mosquito species, Aedes albopictus. Millions of factory-reared adult males with an artificial triple-Wolbachia infection were released, with prior pupal irradiation of the released mosquitoes to prevent unintentionally released triply infected females from successfully reproducing in the field. This successful field trial demonstrates the feasibility of area-wide application of combined IIT-SIT for mosquito vector control.

5.
Nat Prod Res ; : 1-6, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31359767

RESUMO

Three new acenaphthene derivatives cis-3-(4'-methoxyphenyl)-acenaphthene-1, 2-diol (1), trans-(1S, 2S)-3-phenyl-acenaphthene-1, 2-diol (2) and 8-(4-hydroxyphenyl)-2H-acenaphthylen-1-one (3) in company with six known compounds were isolated from the 70% ethanol extract of the rhizomes of Musa basjoo. Those chemical constituents were separated and purified by macroreticular resin, silica gel, Toyopearl HW-40F, SephadexLH-20 and other chromatographic methods, respectively. The chemical structures of new compounds were elucidated by HR-ESI-MS, 1H NMR, 13C NMR, HMQC, HMBC spectrum and specific optical rotations. Compound 4 was isolated for the first time from the genus Musa and compound 7 was firstly assigned the carbon spectrum. Furthermore, the cytotoxic activity of compounds 1-9 against WM9, MDA-MB231, HeLa, K562, DU145 and PC3 was screened with cisplatin as a positive control. Compound 9 showed promising cytotoxic activities with IC50 values of 2.65 ± 0.38 µM against the HeLa cell lines, while compound 8 possessed significant cytotoxicity with IC50 values of 6.51 ± 0.44, 18.54 ± 0.68 and 7.98 ± 1.44 µM against the HeLa, MDA-MB231 and WM9 cell lines, respectively.

6.
Med Sci Monit ; 25: 4933-4940, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31269009

RESUMO

BACKGROUND We discuss the presentation and management of extracranial carotid artery aneurysms (ECAAs) and to develop a new type of classification. MATERIAL AND METHODS A retrospective review of 35 ECAAs patients who were admitted in our institution from January 2010 to June 2016 was conducted. The mean follow-up period was 25.58±22.13 months. RESULTS During the study period, 35 aneurysms were diagnosed and treated (mean age, 50.8±15.6 years; 15 men). There were 28 true aneurysms, 5 false aneurysms, and 2 dissecting aneurysms. A total of 16 patients with true aneurysms underwent open surgical treatment (group 1), whereas 15 received endovascular management, including all false and dissecting aneurysms (group 2). The remaining 4 true aneurysms were treated with hybrid operation (group 3). The patency rates of groups 1, 2, and 3 were 100%, 93.3%, and 100%, respectively. According to the Peking Union Medical College Hospital (PUMCH) Classification, all 24 cases of type Ia aneurysms were treated by either open surgery and/or endovascular treatment, whereas all 3 type Ib cases were treated solely by open surgery. All 5 type IIa patients were treated by endovascular treatment, with the exception of 1 failure that was transferred to hybrid operation. All 3 type IIb patients were treated by hybrid operation. CONCLUSIONS Open surgery was more frequently feasible in true aneurysms, and endovascular surgery was the first choice for false and dissecting aneurysms. Hybrid operation was available for complicated cases. The PUMCH classification may be helpful for selection of management strategies for ECAAs.

7.
Biomed Chromatogr ; : e4637, 2019 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-31256429

RESUMO

Bletilla striata (Thunb.) Reichb. f. (Orchidaceae), also known as Bai-ji, is a traditional Chinese herb that is widely used in Asia to treat hematemesis, hemoptysis, traumatic bleeding and other similar disorders. Most studies have focused on the pharmacological activities of polysaccharide extracts from B. striata. Our previous studies found that the nonpolysaccharide fraction from B. striata extract also has a hemostatic effect; however, the active constituents responsible for this pharmacological action are unclear. Thus, the metabolic profiles of the nonpolysaccharide fraction were investigated in Sprague-Dawley rats and intestinal bacteria models using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Mass data were acquired by the MSE method. Eight components including five prototypes and three metabolites were identified in rat biofluids after oral administration of the nonpolysaccharide fraction. The parent compounds underwent various metabolic processes, including hydrolysis, deglucosylation, glycosylation and sulfate conjugation. The results not only reveal the possible metabolic pathway, but also indicate the potential pharmacological components. Further mechanistic studies using nonpolysaccharide compounds of the B. striata extract are required to obtain potential candidate compounds.

8.
Gene ; 716: 144010, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31352009

RESUMO

Alternative splicing can generate multiple protein messages from a single gene and has emerged as an important mechanism to regulate cancer pathways. The human SAT1 gene produces two transcript variants: one translates spermidine/spermine N-1 acetyltransferase (SSAT1), the rate-limiting enzyme in the catabolism of polyamines, and the other generates SSATX, which has largely unknown biological functions. Here, we used experimental data and analyses of several melanoma transcriptome datasets to reveal that SSATX is weakly expressed in melanoma cells. SSATX knockdown promoted the proliferation, migration, and invasion of human melanoma cells via the activation of the Wnt signaling pathway in a manner that was independent of SSAT1 expression. Based on our data, we propose that SSATX functions as a long non-coding RNA prior to its degradation in melanoma cells. Overall, our findings indicate that SSATX acts as a tumor suppressor, which may aid the future diagnosis and treatment of melanoma.


Assuntos
Melanoma/genética , RNA Longo não Codificante/fisiologia , Acetiltransferases/genética , Processamento Alternativo , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Regulação para Baixo , Técnicas de Silenciamento de Genes , Humanos , Melanoma/metabolismo , Melanoma/patologia , Invasividade Neoplásica , RNA Longo não Codificante/genética , Via de Sinalização Wnt
9.
Bioorg Med Chem ; 27(16): 3707-3721, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31301948

RESUMO

The deficiency of nucleos(t)ide analogues (NAs) as anti-hepatitis B virus (HBV) drugs in clinical use is attributable to their insufficient enrichment in liver and non-target organ toxicity. We aimed to develop potent anti-HBV adefovir derivatives with hepatotrophic properties and reduced nephrotoxicity. A series of adefovir mono l-amino acids, mono cholic acid-drug conjugates were designed and synthesized, and their antiviral activity and uptake in rat primary hepatocytes and Na+-dependent taurocholate co-transporting polypeptide (NTCP)-HEK293 cells were evaluated. We isolated compound 6c as the optimal molecular candidate, with the highest antiviral activity (EC50 0.42 µmol/L, SI 1063.07) and highest cellular uptake in primary hepatocytes and NTCP-HEK293 cells. In-depth mechanistic studies demonstrated that 6c exhibited a lower toxicity in HK-2 cells when compared to adefovir dipivoxil (ADV). This is because 6c cannot be transported by the human renal organic anion transporter 1 (hOAT1). Furthermore, pharmacokinetic characterization and tissue distribution of 6c indicates it has favorable druggability and pharmacokinetic properties. Further docking studies suggested compounds with ursodeoxycholic acid and l-amino acid groups are better at binding to NTCP due to their hydrophilic properties, indicating that 6c is a potential candidate as an anti-HBV therapy and therefore merits further investigation.

10.
J Pharm Sci ; 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31348935

RESUMO

Research on pharmaceutical pediatric powder-for-suspension formulations mainly focuses on chemical and physical stability of the active pharmaceutical ingredient. However, the chemical stability of excipients could also play a key role in governing the quality and performance of the product. The suspending agents that are added into formulations to suspend the active pharmaceutical ingredient particles are critical to ensure the suspension dose accuracy. In this article, we investigate the chemical stability of the suspending agent-xanthan gum-in the presence of other excipients, particularly commonly used acid modifiers (i.e., citric acid, malic acid, succinic acid, and fumaric acid) in pediatric powder-for-suspension formulations. We observed that some of the acid modifiers catalyze cross-linking of xanthan gum during accelerated stability studies in powder blends, which significantly decreases the viscosity of the corresponding constituted suspension, resulting in poor suspendability and dose inaccuracy. Furthermore, we found that the cross-linking of xanthan gum is acid-dependent and that a careful selection of acid modifiers can mitigate the degradation issues of xanthan gum. Finally, we characterized the cross-linked xanthan gum using Fourier transform infrared spectroscopy and solid-state nuclear magnetic resonance and discussed the possible degradation mechanisms.

11.
Zhongguo Zhong Yao Za Zhi ; 44(10): 2156-2162, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31355575

RESUMO

Ultra performance liquid chromatography coupled with time-of-flight mass spectrometry( UPLC-Q-TOF-MS/MS) method was applied to analyze the prototypes and metabolites of the effective components of Polygonum orientale in SD rat serum and urine. The separation was performed on Agilent Eclipse Plus C_(18) column( 2. 1 mm×100 mm,1. 8 µm),with 0. 1% formic acid solution( A)-acetonitrile( B) as the mobile phase for gradient elution. Mass spectrometry data of biological samples were obtained under positive and negative electrospray ion mode. By comparing chromatogram differences between blank samples and drug treatment samples,prototype components and metabolites of the effective components of P. orientale extract were identified. The results showed that 12 metabolites were detected in serum and 26 metabolites in urine( including cross-components) of rats. The main metabolic pathways included hydrogenation,hydroxylation,glucuronidation,sulfation reaction,and methylation-glucuronidation,etc. The method established in this study was reliable and effective for studying the metabolic characteristics of the effective components of P. orientale in rats,and it can provide a reference for further studies on therapeutic material basis of this herb.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Flores/química , Compostos Fitoquímicos/sangue , Compostos Fitoquímicos/urina , Polygonum/química , Animais , Cromatografia Líquida de Alta Pressão , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem
12.
Biochem Biophys Res Commun ; 514(1): 323-328, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31036323

RESUMO

PURPOSE: To investigate the protective effects of miR-301 in exosomes secreted by bone mesenchymal stem cells (BMSCs) on rats' myocardial infarction (MI). METHODS: After isolation and culture, BMSCs were identified using flow cytometry. Then exosomes were then isolated. Rats MI models were established and they were divided into 4 groups: Sham group, Model group (injected with PBS), BMSC-Exos group (injected with exosomes secreted by BMSCs), BMSC-301-Exos group (injected with exosomes secreted by BMSCs transfected with miR-301 mimics). Cardiac function was assessed by cardiac echocardiography. Myocardial infarct area was measured by Masson trichrome staining mRNA and proteins expression were measured by qRT-PCR and western blot. Exosome morphology and myocardial cells autophagy were observed by transmission electron microscopy. RESULTS: BMSCs were obtained. Rat MI models were successfully established. After rats were injected with exosomes secreted by BMSCs transfected with miR-301 mimics, MI tissues were found to have much higher miR-301 expression, LVEF, LVFS, P62 expression, and remarkably lower LVESD, LVEDD, MI area, LC3-II/LC3-I ratio and autophagosomes numbers compared with BMSC-Exos group (all P < 0.05). CONCLUSION: miR-301 in exosomes secreted by BMSCs protected MI by inhibiting myocardial autophagy.

13.
J Invest Surg ; : 1-6, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31109212

RESUMO

BACKGROUND: Whether there is a quantitative correlation between platelet microparticles (PMPs)/calpain and infarction area is still unclear. Whether present antiplatelet agents can improve myocardial infarction by influencing PMPs need to be revealed. The object of our study was to answer those questions. METHODS: Male Wistar rats were used for all studies. All rats were randomly divided into five groups: sham-operated group, myocardial infarction group (blank control group), aspirin intervention group, aspirin combined with clopidogrel intervention group, and aspirin combined with ticagrelor intervention group. Venous blood and hearts were collected at day 7 following MI. ELISA was applied to detect PMPs level. Infarction size was determined by TTC staining method. The comparisons of multiple means were tested with analysis of variance. And the two-two comparisons among the means were done by Student-Newman-Keuls and LSD method. RESULTS: PMPs level and infarction area did not differ between aspirin combined with clopidogrel intervention group and aspirin combined with ticagrelor intervention group. However, significant differences were detected between any two other groups. PMPs were decreased more in dual antiplatelet intervention group. Pearson correlation analysis showed a strong correlation between PMPs and infarction area (r = 0.90) as well as calpain 10 and infarction area (r = 0.84). We created a regression model: y = 4.61 + 0.28*x (y: infarction area, x: PMPs) to assess myocardial infarction area by PMPs level. CONCLUSIONS: Antiplatelet agents may decrease infarction areas by modifying PMPs. There was a strong correlation between PMPs and infarction area. Therefore, PMPs could be used as a tool to assess infarction area.

14.
Wei Sheng Yan Jiu ; 48(3): 403-412, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31133125

RESUMO

OBJECTIVE: To study the lunch quality and physical development status of primary school students in a certain area of Wuhan City, and to provide the scientific basis for improving the nutritional status of school-age children. METHODS: A total of 1001 students of third to sixth grade from two primary schools in Wuhan were enrolled in this study. The three-day lunch meal survey and physical examination were conducted, and students' lunch at school were recorded by meal review. The lunch intake was compared with the standard, and the correlation between nutrient intake and school-age children's height and weight was analyzed. RESULTS: The height of the subjects was(139.81±8.87) cm and the body weight was(35.91±9.44) kg. The average protein intake at lunch of all age groups reached 40% estimated average requirement(EAR), and vitamin B1, vitamin B2, vitamin C, calcium, selenium and other nutrients were seriously inadequate; all age groups of animal meat intake reached the standard. And fish, shrimp, eggs, soybeans and nuts, milk were lack of intake; energy of lunch, carbohydrates, vitamin A, vitamin C, iron intake were correlated with height and weight of school-age children(P<0.05). CONCLUSION: There are some problems such as micronutrient deficiency and unbalanced diet in school-age children aged 9-12 in Wuhan. Physical development did not reach the national average level.


Assuntos
Serviços de Alimentação , Almoço , Animais , Criança , Dieta , Ingestão de Energia , Humanos , Valor Nutritivo , Instituições Acadêmicas
15.
Cell Biol Int ; 43(10): 1102-1112, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31066128

RESUMO

MicroRNAs (miRNAs) are a class of nonprotein-encoding RNAs of ~22 nucleotides in length that bind to or complement each other with a target gene messenger RNA (mRNA) to promote mRNA degradation or inhibit translation of the target mRNA. The protein required [such as Toll-like receptor (TLR) proteins] is controlled at an optimal level. By affecting protein translation, miRNAs have become powerful regulators of biological processes, including development, differentiation, cell proliferation, and apoptosis. MiRNAs are involved in the regulation of proliferation, migration, and apoptosis of vascular smooth muscle cells (VSMCs), thereby affecting the formation of atherosclerosis (AS). In recent years, the role and mechanism of miRNAs involved in AS development in VSMCs have been studied extensively. In the current study, the results and progress in miRNA research are reviewed.

16.
Nutr Cancer ; 71(6): 1007-1018, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31032633

RESUMO

Resistance to chemotherapy drugs, such as adriamycin (ADR), is a common problem in acute myeloid leukemia (AML) patients. We hypothesized that the natural compound resveratrol (Res) may reverse AML drug resistance through the PI3K/Akt/Nrf2 pathway. We investigated the in vitro effect of Res using human promyelocytic leukemia cells (HL-60) and the ADR-resistant cell line (HL-60/ADR) and treated with either Res or ADR + Res. Cellular proliferation inhibition rate, auto-fluorescence intensity of ADR in HL-60/ADR cells and HL-60 cells, mRNA expression of Nrf2 and the drug-resistant gene MRP1, and protein expression of PI3K, Akt, p-Akt, Nrf2, and MRP1 were measured. Results showed ADR + Res had a more significant inhibitory effect than ADR alone on HL-60/ADR cells. Auto-fluorescence intensity of ADR in HL-60/ADR cells treated with ADR + Res significantly increased. No difference of the auto-fluorescence intensity of ADR was observed in HL-60 cells treated with ADR and ADR + Res. mRNA expression of Nrf2 and MRP1 significantly decreased in HL-60/ADR cells treated with both Res and ADR + Res; protein expression of PI3K, p-Akt, Nrf2, and MRP1 significantly decreased in HL-60/ADR cells treated with PI3K inhibitor, Res and ADR + Res. In conclusion, Res reverses the drug resistance of AML HL-60/ADR cells through regulation of the PI3K/Akt/Nrf2 signaling pathway and MRP1 expression.

17.
Sci Rep ; 9(1): 5980, 2019 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-30979948

RESUMO

We developed an optical coherence tomography angiography technique by improving the speckle contrast algorithm and the imaging process. This technique, which can achieve angiogenesis imaging in vivo without increasing trauma, was used to evaluate the microvasculature in limb ischemia mice. Sixteen left hindlimb ischemia mice were randomly allocated into CuSO4 and saline groups. Within 7 days after treatment, limb ischemic damage, temperature and histological staining were assessed by traditional methods. In addition, angiogenesis was evaluated using an optical coherence tomography angiography system in vivo. All results were compared. After 7 days of treatment, both the ischemic tissue damage score and temperature ratio of the CuSO4 group were significantly higher than those of the control group (all P < 0.05). The number of CD31-positive endothelial cells in the CuSO4 group (0.1836 ± 0.0153) was significantly greater than that in the saline control group (0.0436 ± 0.0069) (P < 0.001). Optical coherence tomography angiography showed that the vessel area density of mice in the CuSO4 group (0.2566 ± 0.0060) was significantly greater than that of mice in the control group (0.2079 ± 0.0202) (P = 0.027). Optical coherence tomography angiography represents a practical and effective method for observing angiogenesis in the mouse hindlimb in vivo without increasing trauma.

18.
J Clin Invest ; 129(6): 2237-2250, 2019 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-31033484

RESUMO

Exosomes, as functional paracrine units of therapeutic cells, can partially reproduce the reparative properties of their parental cells. The constitution of exosomes, as well as their biological activity, largely depends on the cells that secrete them. We isolated exosomes from explant-derived cardiac stromal cells from patients with heart failure (FEXO) or from normal donor hearts (NEXO) and compared their regenerative activities in vitro and in vivo. Patients in the FEXO group exhibited an impaired ability to promote endothelial tube formation and cardiomyocyte proliferation in vitro. Intramyocardial injection of NEXO resulted in structural and functional improvements in a murine model of acute myocardial infarction. In contrast, FEXO therapy exacerbated cardiac function and left ventricular remodeling. microRNA array and PCR analysis revealed dysregulation of miR-21-5p in FEXO. Restoring miR-21-5p expression rescued FEXO's reparative function, whereas blunting miR-21-5p expression in NEXO diminished its therapeutic benefits. Further mechanistic studies revealed that miR-21-5p augmented Akt kinase activity through the inhibition of phosphatase and tensin homolog. Taken together, the heart failure pathological condition altered the miR cargos of cardiac-derived exosomes and impaired their regenerative activities. miR-21-5p contributes to exosome-mediated heart repair by enhancing angiogenesis and cardiomyocyte survival through the phosphatase and tensin homolog/Akt pathway.

19.
Chem Pharm Bull (Tokyo) ; 67(7): 725-728, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30982797

RESUMO

Eighteen novel chalcone derivatives containing indole and naphthalene moieties (2-19) were synthesized and characterized by 1H-NMR, 13C-NMR and high resolution (HR)-MS spectra. All compounds were evaluated for their in vitro cytotoxic potential against human hepatocellular carcinoma (HepG2), human colon carcinoma (HCT116) and human breast adenocarcinoma (MCF-7) cell lines. Among them, compound 2, 3, 4 and 7 showed potent activities against tested cancer cell lines. More significantly, compound 7 exhibited the most potent cytotoxic activity against HepG2, HCT116 and MCF-7 with IC50 values of 0.65, 1.13 and 0.82 µM, respectively. Furthermore, flow cytometry analysis indicated that compound 7 arrested cancer cells in G2/M phase. The compound 7 also displayed significant inhibition of tubulin polymerization (IC50 = 3.9 µM). Finally, molecular docking studies were performed to explore the possible interactions between compound 7 and tubulin binding pockets.


Assuntos
Antineoplásicos/síntese química , Chalconas/química , Indóis/química , Naftalenos/química , Moduladores de Tubulina/síntese química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Sítios de Ligação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Chalconas/metabolismo , Chalconas/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Simulação de Acoplamento Molecular , Estrutura Terciária de Proteína , Relação Estrutura-Atividade , Tubulina (Proteína)/química , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/metabolismo , Moduladores de Tubulina/farmacologia
20.
Asian J Surg ; 2019 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-30914154

RESUMO

To provide a meta-analysis of studies evaluating long-term all-cause mortality, aneurysm-related mortality and re-intervention after open or endovascular repair for abdominal aortic aneurysm. Electronic bibliographic sources were interrogated using a combination of free text and controlled vocabulary searches to identify studies comparing the long-term outcomes of open and endovascular repair for abdominal aortic aneurysm. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement standards. Fixed effect or random effects models were used. We retrieved 4 randomized controlled trials (RCTs; 2,783 patients), 7 nonrandomized trials (86,035 patients). The primary outcome was all-cause mortality. Heterogeneity was high and publication bias could not be excluded. Despite these limitations, the analysis showed that open and endovascular abdominal aortic aneurysm repair had similar all-cause mortality (OR 1.16, 95% CI, 0.89-1.51) over 5 years follow up, which was maintained after at least 10 years of follow-up (OR 0.87, 95% CI, 0.73-1.03). There was no significant difference in aneurysm-related mortality by 5 years or longer follow-up. A significantly lower proportion of patients undergoing open repair required reintervention (OR 0.38, 95% CI 0.24-0.64), which was maintained over 5 years of follow-up. There is no long-term survival difference between the patients who underwent open or endovascular aneurysm repair. There is significantly higher risk of reinterventions after endovascular aneurysm repair.

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