Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 45
Filtrar
2.
Nat Prod Res ; : 1-5, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172306

RESUMO

A convenient and selective alkylation of icaritin has been developed. The methodology involved initial formation of ß-anhydroicaritine (3) under acidic conditions followed by selective methylation at the C-3 position and then alkylation at C-5 position. Several alkylated ß-anhydroicaritine derivatives were synthesised using this methodology. These newly synthesised derivatives, especially the compounds 5b, 5c and 5j, significantly suppressed cell proliferation when tested against cancer cell lines in vitro. Compound 5j (R = Bn) exhibited a competitive inhibition against MCF7 in vivo compared to tamoxifen.

3.
Nat Prod Res ; : 1-5, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33078626

RESUMO

In this paper, a series of novel derivatives of camptothecin substituted norcantharimide was designed by mimic strategy. These compounds were synthesized in moderate yields by directly coupling CPT with N-amino acid norcantharimides. Their cytotoxicity to four human tumour cell lines (HepG2, BGC-803, SW480 and PANC-1) and normal human cell lines L-O2 and HIEC was evaluated. The synthesized CPT substituted norcantharimide analogs (3g and 3f) showed better anti-hepatocarcinoma activity than CPT. Compounds 3d, 3e, 3g, 3h and 3i also showed strong inhibition activity against BGC803.

4.
Eur J Med Genet ; 63(11): 104021, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32755715

RESUMO

Spondyloepimetaphyseal dysplasias (SEMDs), which comprise a heterogeneous group of autosomal-dominant, autosomal-recessive and X-linked recessive disorders, are characterized by anomalies of the spine, the epiphyses and metaphyses of the long bones, resulting in short stature and osteoarthritic changes of the joints. UFSP2 gene encodes a highly conserved cysteine protease which cleaves two C-terminal residues from ubiquitin-fold modifier 1, an ubiquitin-like post-translational modifier protein. In 2018, Di Rocco, M reported for the first time that a novel heterozygous variant exon 11: c.1277A > C of the UFSP2 gene was the cause to spondyloepimetaphyseal dysplasia mainly manifested as: short stature, anterior vertebral dysplasia, hip dysplasia, flat vertebra, spinal metaphyseal dysplasia, irregular acetabular apex, distal femoral metaphyseal dysplasia, proximal tibial metaphyseal dysplasia, osteoarthritis and so on. In this report, we describe a boy with spondyloepimetaphyseal dysplasia due to a novel mutation exon 11: c.1283A > G (leading to p. H428R) of the UFSP2 gene. This is the second report to describe children with SEMDs associated with an UFSP2 variant. However, it is the first to describe a UFSP2 gene mutation exon 11: c.1283A > G (leading to p. H428R). Our findings of a novel heterozygous mutation of UFSP2 gene add to the list of 2 reported heterozygous mutations of UFSP2 which led to hereditary osteopathy.

5.
Arch. bronconeumol. (Ed. impr.) ; 56(6): 360-364, jun. 2020. tab
Artigo em Espanhol | IBECS-Express | IBECS | ID: ibc-FGT-4843

RESUMO

BACKGROUND: High-altitude pulmonary edema (HAPE) is a kind of non-cardiogenic edema with high incidence and life-threatening. This study was designed to explore the association of LINC-PINT and LINC00599 polymorphisms with HAPE susceptibility. METHODS: This study included 244 HAPE patients and 243 age-, sex-matched healthy controls from the Chinese population. The genotypes of polymorphisms were detected using the Agena MassARRAY. The relationship between polymorphisms and HAPE risk was evaluated using a chi2 test with an odds ratio (OR) and 95% confidence intervals (CIs) in multiple genetic models. RESULTS: We observe a significant association between the rs157928 and decreased HAPE risk in genotype model (OR = 0.65, 95% CI = 0.43-0.98, p = 0.038). The subgroup analysis results indicated that rs2272026 was associated with a decreased risk of HAPE in younger patients with age ≤ 32 (codominant model: p = 0.006; recessive model: p = 0.005 additive model: p = 0.018; and allele model: p = 0.012; rs72625676, codominant model: p = 0.038; recessive model: p = 0.037). Among patients older than 32 years, there was a significantly increased risk of HAPE associated with the rs2272026 and rs1962430 (rs2272026: genotype model: p = 0.049; recessive model: p = 0.029; rs1962430: genotype model: p = 0.024; recessive model: p = 0.020). Nevertheless, rs157928 had relationship with significantly reducing the risk of HAPE in the genotype model (p = 0.018). CONCLUSION: Our study suggests that LINC-PINT and LINC00599 polymorphisms are associated with HAPE susceptibility in Chinese population


ANTECEDENTES: El edema pulmonar de altitud (EPA) es un tipo de edema no cardiogénico con una incidencia alta y es potencialmente mortal. Este estudio se diseñó para explorar la asociación entre los polimorfismos de LINC-PINT y LINC00599 y la susceptibilidad al EPA. MÉTODOS: Este estudio incluyó a 244 pacientes con EPA y 243 controles sanos de la misma edad y sexo, todos de origen chino. Los genotipos de los polimorfismos se detectaron utilizando el MassARRAY de AgenaTM La relación entre los polimorfismos y el riesgo de EPA se evaluó utilizando el test de la CHi2 con el odds ratio (OR) e intervalos de confianza (IC) del 95% en múltiples modelos genéticos. RESULTADOS: Observamos una asociación significativa entre el rs157928 y una disminución del riesgo de EPA en el modelo genotípico (OR = 0,65, IC del 95% = 0,43-0,98, p = 0,038). Los resultados de los análisis por subgrupos indicaron que el rs2272026 se asociaba a una disminución del riesgo de EPA en pacientes jóvenes de ≤ 32 años (modelo codominante: p = 0,006; modelo recesivo: p = 0,005; modelo aditivo: p = 0,018; y modelo por alelos: p = 0,012 para rs72625676, modelo concomitante: p = 0,038; modelo recesivo: p = 0,037). Entre los pacientes mayores de 32 años, se encontró un riesgo aumentado de EPA de manera significativa asociado a los rs2272026 y rs1962430 (rs2272026: modelo genotípico: p = 0,049; modelo recesivo: p = 0,029; rs1962430: modelo genotípico: p = 0,024; modelo recesivo: p = 0,020). Sin embargo, el rs157928 tenía relación con una reducción significativa del riesgo de EPA en el modelo genotípico (p = 0,018). CONCLUSIÓN: Nuestro estudio sugiere que los polimorfismos de LINC-PINT y LINC00599 están asociados a la susceptibilidad de EPA en la población china

6.
Biosci Rep ; 40(5)2020 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-32329795

RESUMO

BACKGROUND: The present study aimed to investigate the roles of insulin related gene IGF2BP2, HMG20A, and HNF1B variants in the susceptibility of Type 2 diabetes mellitus (T2DM), and to identify their association with age, gender, BMI, and smoking and alcohol drinking behavior among the Han Chinese population. METHODS: About 508 patients with T2DM and 503 healthy controls were enrolled. Rs11927381 and rs7640539 in IGF2BP2, rs7178572 in HMG20A, rs4430796, and rs11651052 in HNF1B were genotyped by using the Agena MassARRAY. Odds ratio (OR) and 95% confidence intervals (CI) were calculated by logistic regression. RESULTS: We found that HMG20A rs7178572 (OR = 1.25, P = 0.015) and HNF1B rs11651052 (OR = 1.26, P = 0.019) increased the risk of T2DM. Rs7178572, rs4430796, and rs11651052 might be related to the higher T2DM susceptibility not only by itself but also by interacting with age, gender smoking, and alcohol drinking. Rs11927381 also conferred the higher T2DM susceptibility at age ≤ 59 years. Besides, rs7178572-AA (P = 0.032) genotype and rs11651052 GG (P = 0.018) genotype were related to higher glycated hemoglobin and insulin level, respectively. CONCLUSION: Specifically, we first found that rs11927381, rs7640539, and rs11651052 were associated with risk of T2DM among the Han Chinese population. We also provide evidence that age, gender, BMI, smoking, and drinking status have an interactive effect with these variants on T2DM susceptibility.

7.
Int Immunopharmacol ; 83: 106401, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32240943

RESUMO

Rheumatoid arthritis (RA) is a chronic, inflammatory synovitis dominated systemic disease with unknown etiology. The purpose of this study was to determine the relationship between IL1B polymorphisms and RA risk in a Chinese Han population. Four single-nucleotide polymorphisms (SNPs) of IL1B, rs2853550, rs1143643, rs3136558 and rs16944 were genotyped in 508 RA cases and 494 healthy controls using the Agena MassARRAY method. A genetic model analysis was performed to evaluate the relationships between the variants and RA risk. Haplotype analysis was used to evaluate the potential relationship between the genetic block and RA risk. We determined that rs1143643 was linked to a reduced risk of RA based on the results of the co-dominant model (OR = 0.67, 95%CI: 0.50-0.89, p = 0.006) and the dominant model (OR = 0.73, 95%CI = 0.56-0.96, p = 0.025). On the other hand, rs16944 was associated with an increased risk of RA in the co-dominant model (OR = 1.71, 95%CI = 1.53-1.97, p = 0.029) and the recessive model (OR = 1.41, 95%CI = 1.05-1.88, p = 0.021). Among individuals older than 50 years, we observed that rs2853550 was associated with an increased risk of RA, and that rs1143643 decreased RA risk. Furthermore, rs1143643 was associated with a decreased RA risk in female patients. However, rs16944 increased RA risk in both the co-dominant and the additive models in different age subgroups. In addition, rs16944-GA increased RA risk in males in the co-dominance model and rs16944-AA increased RA risk in females in the additive model. These results suggested that rs2853550, rs1143643, and rs16944 in the IL1B gene are associated with RA risk.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32311112

RESUMO

Personalized medicine, the best treatment suited for an individual, is a hot field of clinical research in the world. Many recent studies have shown that genetic variations had a great influence on the treatment. The study aimed to identify the distribution differences of very important pharmacogene (VIP) variants between the Tibetan population and the 26 populations. Based on the PharmGKB database, we successfully genotyped 50 VIP variants located in 27 genes in the Tibetan population. We also compared the genotype frequencies of VIP variants between Tibetan and the 26 populations from the 1000 Genomes project. Without adjustment, the Chi-square test showed that the only significant variant between Tibetans and every other group was rs1801159 in dihydropyrimidine dehydrogenase (DPYD), followed by rs1800566 in NAD(P)H quinone dehydrogenase 1 (NQO1) and rs1051296 in solute carrier family 19 member 1 (SLC19A1). After Bonferroni's multiple adjustments, the genotype frequencies distribution of DPYD rs1801159 was found to be different in Tibetans compared to 26 groups, apart from ACB and ASW. Moreover, genetic structure/F-statistics (Fst) analysis and the phylogenetic tree illustrated that Tibetans had a closer affinity with CDX, CHB, CHS, JPT and KHV. Our data will complement pharmacogenomics information of the Tibetan population and provide theoretical support for the realization of individualized medical treatment for Tibetans in the future.

9.
Pharmacol Res ; 153: 104637, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31935454

RESUMO

The Aidi injection contains multiple active ingredients, including astragaloside (Re, Rb1, and Rg1), ginsenoside, cantharidin, elentheroside E, and syringin, and it is administered with vinorelbine and cisplatin (NP) to treat non-small-cell lung carcinoma (NSCLC). In this study, we performed a systematic review and meta-analysis to determine the clinical efficacy and safety of the Aidi injection with NP, and the optimal threshold and treatment regimen to produce the desired responses. We collected all studies regarding the Aidi injection with NP for NSCLC from Chinese and English databases (up to April 2019). Risk of methodological bias was evaluated for each study. Data for analysis were extracted using a standard data extraction form. Evidence quality was assessed following the Grading of Recommendations Assessment, Development and Evaluation approach. We included 54 trials containing 4,053 patients for analysis. Combining the Aidi injection with NP significantly increased the objective response rate (odds ratio [OR], 1.32; confidence interval [CI], 1.23, 1.42), disease control rate (OR, 1.14; CI, 1.11, 1.18), and quality of life (OR, 1.80; CI, 1.61, 1.98), with decreased risks of myelosuppression, neutropenia, thrombocytopenia, anemia, gastrointestinal reaction, and liver dysfunction. For patients with a Karnofsky Performance Status score of ≥60, the Aidi injection (50 mL/day, two weeks/cycle, with two to three cycles) treatment with vinorelbine (25 mg/m2) and cisplatin (30-35 mg/m2 or 40-50 mg/m2) might be the optimal regimen for producing the desired tumor response and achieving a good safety level. Most results were robust, and their quality was moderate. The results suggest that administration of the Aidi injection and concomitant NP is beneficial to NSCLC, and provide evidence for the optimal threshold and treatment regimen that may improve tumor response with a good safety level.

10.
Biosens Bioelectron ; 150: 111862, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31740256

RESUMO

Salmonella is the leading risk factor in food safety. Rapid, sensitive and accurate detection of Salmonella is a key to prevent and control the outbreaks of foodborne diseases caused by Salmonella. In this study, we reported a colorimetric biosensor for ultrasensitive detection of Salmonella Typhimurium using a magnetic grid separation column to efficiently separate target bacteria from large volume of sample and platinum loaded zeolitic imidazolate framework-8 (Pt@ZIF-8) nanocatalysts to effectively amplify biological signal. The target Salmonella cells in large volume of sample were first separated and concentrated using the magnetic grid separation column with immune magnetic particle chains, then conjugated with the immune Pt@ZIF-8 nanocatalysts to mimic peroxidase for catalysis of hydrogen peroxide-3,3',5,5'-tetramethylbenzidine, and finally determined by measuring the catalysate at characteristic wavelength of 450 nm. This proposed biosensor was able to separate ∼70% of target Salmonella cells from 50 mL of bacterial sample and quantitatively detect Salmonella from 101 to 104 CFU/mL in 2.5 h with the lower detection limit of 11 CFU/mL. The mean recovery for Salmonella in spiked chicken carcass was about 109.8%. This new magnetic grid separation method was first time reported for efficient separation of target bacteria from very large volume of sample to greatly improve the sensitivity of this biosensor and could be used with various biosensing assays for practical applications in routine detection of foodborne pathogens without any bacterial pre-enrichment.


Assuntos
Técnicas Biossensoriais , Microbiologia de Alimentos , Salmonella/isolamento & purificação , Animais , Galinhas/microbiologia , Colorimetria , Contaminação de Alimentos , Humanos , Magnetismo , Platina/química , Salmonella/patogenicidade , Zeolitas/química
11.
Arch Bronconeumol ; 56(6): 360-364, 2020 06.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31761491

RESUMO

BACKGROUND: High-altitude pulmonary edema (HAPE) is a kind of non-cardiogenic edema with high incidence and life-threatening. This study was designed to explore the association of LINC-PINT and LINC00599 polymorphisms with HAPE susceptibility. METHODS: This study included 244 HAPE patients and 243 age-, sex-matched healthy controls from the Chinese population. The genotypes of polymorphisms were detected using the Agena MassARRAY. The relationship between polymorphisms and HAPE risk was evaluated using a χ2 test with an odds ratio (OR) and 95% confidence intervals (CIs) in multiple genetic models. RESULTS: We observe a significant association between the rs157928 and decreased HAPE risk in genotype model (OR=0.65, 95% CI=0.43-0.98, p=0.038). The subgroup analysis results indicated that rs2272026 was associated with a decreased risk of HAPE in younger patients with age ≤32 (codominant model: p=0.006; recessive model: p=0.005 additive model: p=0.018; and allele model: p=0.012; rs72625676, codominant model: p=0.038; recessive model: p=0.037). Among patients older than 32 years, there was a significantly increased risk of HAPE associated with the rs2272026 and rs1962430 (rs2272026: genotype model: p=0.049; recessive model: p=0.029; rs1962430: genotype model: p=0.024; recessive model: p=0.020). Nevertheless, rs157928 had relationship with significantly reducing the risk of HAPE in the genotype model (p=0.018). CONCLUSION: Our study suggests that LINC-PINT and LINC00599 polymorphisms are associated with HAPE susceptibility in Chinese population.

12.
Brain Behav ; 10(2): e01503, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31872978

RESUMO

AIMS: Stroke is a complicated neurological disease and the second leading cause of death in the world. We aimed to investigate the association between CYP24A1 genetic polymorphisms and ischemic stroke risk. METHODS: In this case-control study, four single-nucleotide polymorphisms of CYP24A1 were selected and genotyped by MassARRAY platform in Chinese Han population. Odds ratios and 95% confidence intervals were calculated via logistic regression analysis with adjustment in genetic models. RESULTS: Our results indicated that CYP24A1 variant (rs1570669) was associated with the decreased risk of ischemic stroke (OR = 0.60, p < .001). Stratification analysis showed that the rs6068816 could enhance the ischemic stroke risk by 1.64 times (OR = 1.64, p = .028), while rs1570669 played protective role (OR = 0.63, p = .044) in age >64 years. The rs2762934 had an increased ischemic stroke susceptibility (OR = 1.62, p = .033); however, rs1570669 might reduce stroke risk (OR = 0.61, p = .015) in age ≤64 years. The rs1570669 depressed ischemic stroke susceptibility both in female and male patients (OR = 0.46, p = .002; OR = 0.69, p = .033, respectively), and rs2296241 would weaken the risk in male (OR = 0.63, p = .012). The rs1570669 was associated with decreased risk of ischemic stroke with hypertension (OR = 0.56, p = .042). CONCLUSION: Our study gave the evidences that CYP24A1 genetic polymorphisms were significantly associated with ischemic stroke patients, which would provide useful information of assessment or possible diagnostic markers for ischemic stroke.

13.
Front Public Health ; 7: 315, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31799230

RESUMO

Background: Cytochrome P450 3A4 (CYP3A4) regulates pharmacokinetic and pharmacodynamic interactions during the process of drug absorption and metabolism, suggesting CYP3A4 plays an important role in drug addiction. However, the association between CYP3A4 polymorphisms and drug addiction risk is still not clear. Methods: This case-control study included 504 drug addicts and 501 healthy controls from Xi'an, China. Four single nucleotide polymorphisms (SNP) in CYP3A4 (rs3735451, rs4646440, rs35564277, and rs4646437) were genotyped by Agena MassARRAY platform. After adjusting by age and gender, we calculated odd ratios (OR) and 95% confidence intervals (CI) by logistic regression to estimate the association between CYP3A4 polymorphisms and drug addiction risk. Results: We found rs4646440 and rs4646437 were associated with decreased risk of drug addiction in codominant (rs4646440: OR = 0.41, 95%CI = 0.19-0.92, p = 0.030; rs4646437: OR = 0.19, 95%CI = 0.04-0.87, p = 0.032) and recessive (rs4646440: OR = 0.41, 95%CI = 0.19-0.91, p = 0.028; rs4646437: OR = 0.20, 95%CI = 0.04-0.90, p = 0.036) models. Rs3735451 and rs4646437 were associated with drug addiction risk in the subgroup of middle-aged people (44 < age ≤ 59) and elderly people (age ≥ 60), individually. For men, rs3735451, rs4646440, and rs4646437 had strong relationship with decreased risk of drug addiction (p < 0.05). The effects of rs3735451 on drug addiction risk were related to drug-using time (p < 0.05). We also observed one block (rs4646440 and rs35564277) in haplotype analysis. Conclusion: CYP3A4 polymorphisms were associated with drug addiction risk among the Chinese Han population.

14.
Theor Biol Med Model ; 16(1): 20, 2019 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-31865918

RESUMO

Variations of gene expression levels play an important role in tumors. There are numerous methods to identify differentially expressed genes in high-throughput sequencing. Several algorithms endeavor to identify distinctive genetic patterns susceptable to particular diseases. Although these processes have been proved successful, the probability that the number of non-differentially expressed genes measured by false discovery rate (FDR) has a large standard deviation, and the misidentification rate (type I error) grows rapidly when the number of genes to be detected become larger. In this study we developed a new method, Unit Gamma Measurement (UGM), accounting for multiple hypotheses test statistics distribution, which could reduce the dependency problem. Simulated expression profile data and breast cancer RNA-Seq data were utilized to testify the accuracy of UGM. The results show that the number of non-differentially expressed genes identified by the UGM is very close to the real-evidence data, and the UGM also has a smaller standard error, range, quartile range and RMS error. In addition, the UGM can be used to screen many breast cancer-associated genes, such as BRCA1, BRCA2, PTEN, BRIP1, etc., provides better accuracy, robustness and efficiency, the method of identification differentially expressed genes in high-throughput sequencing.


Assuntos
Algoritmos , Modelos Estatísticos , Oncogenes , Neoplasias da Mama/genética , Simulação por Computador , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Humanos
15.
Int J Nanomedicine ; 14: 7447-7460, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31686816

RESUMO

Objective: This study aimed to investigate the interaction between the ion-complementary self-assembling peptide RADA16-I and the hydrophobic drug mangiferin (MA), and the potential of the self-assembling peptide to be exploited as a drug carrier of MA. Methods: The RADA16-I-MA suspension was prepared by magnetic stirring, followed by fluorescence spectrophotometry, particle size determination, rheological properties analysis, and in vitro release assay to characterize the interaction between RADA16-I and MA. Then, the effects of in situ MA-loaded hydrogel on the proliferation of KYSE 30 and DLD-1 tumor cells and the toxic effect of the hydrogel on 293T renal epithelial cells were studied by the Cell Counting Kit 8 method. Results: The RADA16-I-MA suspension was formed in water under magnetic stirring; the in situ hydrogel was formed when the suspension was added to PBS. The particle size in the RADA16-I-MA suspension was around 300-600 nm with an average size of 492 nm. Within 24 h, the cumulative release of MA from the RADA16-I-MA hydrogel was about 80%. The release rate of MA from the hydrogel was dependent on the concentration of RADA16-I and the release can be fitted with a first-order kinetic equation. The results suggested that the self-assembling peptide can stabilize MA in water to form a relatively stable suspension; the results also indicated that controlled release of MA from the RADA16-I-MA in situ hydrogel formed from the RADA16-I-MA suspension can be achieved by adjusting the concentration of the peptide in suspension. The cell viability studies showed that the RADA16-I-MA in situ hydrogel not only can maintain or enhance the intrinsic proliferation inhibition effects of MA on tumor cells, but also can reduce the toxicity of MA to normal cells. Conclusion: The self-assembling peptide RADA16-I can be a potential candidate for constructing a delivery system of the hydrophobic drug MA.


Assuntos
Liberação Controlada de Fármacos , Hidrogéis/química , Peptídeos/química , Xantonas/química , Morte Celular , Linhagem Celular , Proliferação de Células , Sobrevivência Celular/efeitos dos fármacos , Coloides/química , Elasticidade , Humanos , Tamanho da Partícula , Reologia , Espectrometria de Fluorescência , Suspensões , Viscosidade
16.
Artif Cells Nanomed Biotechnol ; 47(1): 3961-3975, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31588802

RESUMO

Ion-complementary self-assembling peptides have potential in delivering hydrophobic drugs. This study involved two self-assembling peptides, RADA16-I and RVDV16-I, of which RVDV16-I was a novel self-assembling peptide with different hydrophobic side chains designed from RADA16-I. The purpose of this study was to observe the interaction between different self-assembling peptides and emodin through fluorescence spectrophotometry, CD, SEM and AFM; to construct a preliminary suspension in-situ hydrogel delivery system for emodin with the self-assembling peptides; and to investigate the drug-loading and drug-releasing properties of the self-assembling peptides on emodin. The results showed that both peptides can interact with emodin and the interaction was dominated by hydrophobic interaction. The aqueous solutions of both self-assembling peptides can form relatively stable suspensions with emodin under mechanical stirring, and the suspension can form in-situ hydrogel under physiological condition. In vitro release of emodin from the hydrogels showed a manner of sustained release to some extent. Cell viability studies showed inherent proliferation inhibiting effects of emodin on tumor cells was maintained or enhanced through the in-situ hydrogels. The self-assembling peptides RADA16-I and RVDV16-I had showed promising drug-loading and drug-releasing performance for hydrophobic drugs. It is reasonable to exploit self-assembling peptides as drug carriers for their great potential to improve delivery of hydrophobic drugs.


Assuntos
Antineoplásicos/química , Preparações de Ação Retardada/química , Emodina/química , Hidrogéis/química , Peptídeos/química , Células A549 , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Emodina/administração & dosagem , Emodina/farmacologia , Células Hep G2 , Humanos , Hidrogéis/farmacologia , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular , Suspensões
17.
Oncol Rep ; 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31524264

RESUMO

Oxaliplatin (OXA) is routinely used as the first­line treatment for colorectal cancer (CRC). The addition of OXA to chemotherapy has significantly improved the prognosis of patients with CRC; however, some cases are resistant to OXA. The present study explored the influence of organic cation transporter 3 (OCT3) expression on the effects of OXA on CRC cell viability, and investigated the direct effects of OCT3 on viability, invasion and migration of CRC cells using MTT assay, wound healing assay, reverse transcription­quantitative polymerase chain reaction, inductively coupled plasma mass spectrometry and lentiviral interference. The results demonstrated that OXA cellular concentration and OXA­induced cytotoxicity were significantly increased in response to high expression of OCT3, whereas OCT3 knockdown directly increased the invasion and migration of colon cancer cells. Furthermore, upregulation of OCT3 expression in colon cancer xenografts via treatment with the DNA methyltransferase inhibitor decitabine increased cellular OXA concentration and improved the curative effect of OXA. These results collectively indicated that OCT3 may enhance the effects of OXA in CRC cells and may directly inhibit their invasion and migration. Therefore, OCT3 may be a therapeutic target in patients with CRC.

18.
Mol Genet Genomic Med ; 7(11): e966, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31487124

RESUMO

BACKGROUND: Kidney cancer is the predominant form of malignancy of the kidney and accounts for approximately 3%-4% of all cancers. Renal cell cancer (RCC) represents more than 85% of kidney cancer. It has been reported that genetic factors may predispose individuals to RCC. This study evaluated the association between Acylphosphatase 2 (ACYP2) gene polymorphisms and RCC risk in the Han Chinese population. METHODS: Twelve single-nucleotide polymorphisms (SNPs) in ACYP2 were genotyped using the Agena MassARRAY platform from 293 RCC patients and 495 controls. The Chi-squared test, genetic models, haplotype, and stratification analyses were used to evaluate the association between SNPs and the risk of RCC. The relative risk was estimated using the odds ratio (OR) and 95% confidence interval (CI). RESULTS: We observed that the rs6713088 allele G (OR = 1.26, 95% CI: 1.03-1.53, p = .023) and rs843711 allele T (OR = 1.29, 95% CI: 1.06-1.57, p = .010) were associated with increased RCC risk. Genetic model analyses found that rs843711 was significantly associated with an increased RCC risk under the recessive model and log-additive model after adjusting for age and gender. Haplotype analysis showed that the haplotype "TTCTCGCC" (OR = 0.67, 95% CI: 0.48-0.94, p = .021) was associated with a decreased risk of RCC in the Han Chinese population. Stratification analysis also found that rs6713088 and rs843711 were significantly associated with increased RCC risk. CONCLUSION: In summary, the results suggested that ACYP2 polymorphisms could be used as a genetic marker for RCC. Additional functional and association studies are required to validate our results.


Assuntos
Hidrolases Anidrido Ácido/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Predisposição Genética para Doença , Neoplasias Renais/genética , Neoplasias Renais/patologia , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Feminino , Seguimentos , Estudos de Associação Genética , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
19.
Mol Genet Genomic Med ; 7(8): e770, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31241240

RESUMO

BACKGROUND: Tuberculosis (TB) is a significant worldwide health problem, and is caused by Mycobacteria tuberculosis. Recent studies have suggested that FOXO3 plays vital roles in the risk of immune-related infectious diseases such as TB. METHODS AND RESULTS: The present study aimed to evaluate FOXO3 genetic variants and TB risk. We recruited 510 TB patients and 508 healthy controls in this study. All subjects were genotyped with the Agena MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression adjusted for age and gender. Our result revealed that rs3800229 T/G and rs4946935 G/A genotypes significantly increased the risk of TB (OR = 1.34, 95% CI = 1.04-1.74, p = 0.026; OR = 1.34, 95% CI = 1.03-1.73, p = 0.029, respectively). In stratified analysis according to gender and age, we observed that rs3800229 T/G and rs4946935 G/A genotypes were associated with an increase the risk of TB among males and age ≤41 years, respectively (OR = 1.47, 95% CI = 1.06-2.04, p = 0.022 and OR = 1.45, 95% CI = 1.05-2.02, p = 0.025). CONCLUSIONS: Our study showed that rs3800229 and rs4946935 in FOXO3 were associated with a risk of TB in the Chinese population.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Proteína Forkhead Box O3/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Tuberculose/genética , Adulto , Estudos de Casos e Controles , China , Feminino , Proteína Forkhead Box O3/imunologia , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis , Razão de Chances , Fatores de Risco , Fatores Sexuais , Tuberculose/imunologia
20.
Anticancer Agents Med Chem ; 19(4): 502-508, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30663574

RESUMO

BACKGROUND: Target therapy has been one of the important strategies in new drug discovery and the resulting drug resistance has also been a serious problem for concern. At the same time, there are several cancer genes or pathways operating within a given cancer. Given these two things, the combination therapy will be needed for optimal therapeutic effect. OBJECTIVE: Camptothecin and norcantharidin were thus chosen to construct a dual anticancer drugs assemblies mainly because CPT was the DNA-topoisomerase I inhibitor and norcantharidin could also suppress the cancer cell growth by inhibiting protein phosphatase. The designed conjugate of camptothecin and norcantharidin linked by alanine was expected to have dual target drug properties. METHODS: EDCI/DMAP was chosen as a coupling agent for the coupling of CPT with substituted norcantharidin derivatives and CCK-8 method was used to test the cytotoxicity and intensity on human hepatoma cell line HepG2. Two kinds of enzymes, Top I and CDC 25B were selected to screen the binding affinity in molecular level. RESULTS: Nine of dual targets camptothecin derivatives were smoothly synthesized by twice coupling in the condition of EDCI/DMAP in moderate yield. All of the synthesized compounds were characterized by 1HNMR and 13CNMR spectrum and exhibited strong potent inhibition against Hep G2, SW480, BGC803, and PANC-1 cell line in vitro. The newly synthesized camptothecin compounds, such as 3j and 3i have strengthened inhibition activity compared to camptothecin and norcantharidin. CONCLUSION: We have successfully synthesized a series of novel camptothecin derivatives constructed from three components of camptothecin, alanine and norcantharidin. These compounds not only preserved strong activity against several cancer cell lines in vitro, but also exhibited potential binding affinity to target Top I and CDC 25B. Therefore, these conjugates linked by alanine could suppress cancer cell growth by inhibiting Top I and protein phosphatase simultaneously, which makes it much valuable as a novel bi-functional target drug candidate to develop in vivo.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Camptotecina/análogos & derivados , Inibidores da Topoisomerase I/farmacologia , Antineoplásicos Fitogênicos/química , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Relação Estrutura-Atividade , Inibidores da Topoisomerase I/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA