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1.
Int J Clin Pharm ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32048122

RESUMO

Like other countries, China has been experiencing drug shortages during the past years, including drugs on the National Essential Medicine List and emergency drugs. Drug shortages have raised public concerns in China and have severe impacts on all stakeholders in the supply chain, especially patients and hospitals. Recently, Chinese governments have ramped up several measures to ensure a steady supply of essential and first-aid drugs. In this commentary, we share our experiences of addressing drug shortages at Hunan Province, central China. We focus on the establishment of a provincial drug shortage monitoring center, and the Center's efforts to standardize practices on the management of drug shortages and identify therapeutic alternatives for drugs in short supply based on international best practices.

2.
Clin Case Rep ; 6(10): 1989-1993, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30349713

RESUMO

Twelve days after birth, the child was admitted to hospital because of "poor response, lethargy, and poor appetite for 6 days" and developed into coma immediately. The ventilator is required. The urine had significant maple syrup odor. After different diagnosis, she was diagnosed with classical maple syrup urine disease.

3.
Exp Ther Med ; 15(6): 5001-5006, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29805523

RESUMO

The incidence of congenital hypothyroidism (CH) in newborn infants ranges from 1 in 3,000 to 1 in 4,000. Previous studies have indicated the neuroprotective role of microRNA (miR)-124-3p, however the expression and role of miR-124-3p in CH remain unclear. Therefore, the present study was performed to investigate the role and precise molecular mechanism of miR-124-3p in CH. Propylthiouracil (50 mg/day) was injected into the stomach of pregnant rats from gestational day 15 until parturition in order to establish a thyroid hypofunction model. Newborn rats were divided into the following four groups: The control group; the thyroid hypofunction group; the miR-124-3p mimic group; and the miR-124-3p negative control group. Reverse transcription-quantitative polymerase chain reaction indicated that miR-124-3p was significantly decreased in the hippocampus of the thyroid hypofunction group compared with the control group. Bioinformatics software was used to predict mRNA targets recognized by miR-124-3p and the programmed cell death protein 6 (PDCD6) 3' untranslated region (UTR) was demonstrated to exhibit the seed sequence of miR-124-3p. The interaction between miRNA-124-3p and PDCD6 was then verified using a dual-luciferase reporter assay system. PDCD6 expression was significantly increased in the hippocampus of rats with CH compared with the control group. Flow cytometry was performed to investigate the effects of miR-124-3p on neuronal cell apoptosis and the results indicated that the apoptosis rate in the thyroid hypofunction group was significantly increased compared with the control group; this increase was reversed by transfection with miR-124-3p mimics. Western blot analysis was used to detect the levels of cleaved poly [ADP-ribose] polymerase (PARP), full-length PARP, caspase-3, B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) proteins. The results indicated that the expression of cleaved PARP, caspase-3 and Bax protein were significantly increased and the expression of full-length PARP and Bcl-2 protein was significantly decreased compared with the control group. These effects were reversed by miRNA-124-3p mimic transfection. Taken together, the results of the present study demonstrate that miRNA-124-3p serves a protective role in CH via targeting PDCD6.

4.
Per Med ; 15(3): 167-179, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29790821

RESUMO

BACKGROUND: Colorectal cancer (CRC) represents the third most common type of cancer and the third leading cause of death from cancer around the world. M701 is a CD3/EpCAM bispecific antibody that shows promising cytotoxicity toward CRC cells. AIM: To investigate the influence of immuno-related gene polymorphisms on M701 mediated cytotoxicity to CRC cell HCT116. METHOD: We analyzed the influence of the effect of M701 on the activation and cytotoxicity of peripheral mononuclear blood cells from 129 healthy volunteers with different genotypes. RESULT: When incubated with M701, peripheral mononuclear blood cells from CD247 rs2949655 AA homozygotes showed significantly lower cytotoxicity than those from AG/GG heterozygotes. CONCLUSION: CD247 rs2949655 was significantly associated with the cytotoxicity of M701 to HCT116, which might contribute to personalized medicine of M701.


Assuntos
Anticorpos Biespecíficos/farmacologia , Complexo CD3/genética , Neoplasias Colorretais/genética , Variantes Farmacogenômicos , Complexo CD3/imunologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Molécula de Adesão da Célula Epitelial/imunologia , Genótipo , Células HCT116 , Voluntários Saudáveis , Humanos , Medicina de Precisão
5.
Pharmacogenet Genomics ; 27(9): 337-346, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28731962

RESUMO

Cytochrome P450 oxidoreductase (POR) has played a potential role in the metabolism of drugs and steroids by supplying electrons to microsomal cytochrome P450 (CYP) enzymes. More than 200 different POR mutations and polymorphisms causing more than 130 amino acid changes in the POR protein have been reported since 2004. A503V is a common amino acid sequence variant encoded by POR*28, whereas A287P and R457H are the most common disease-causing mutations in Europeans and Asians, respectively. Polymorphisms in the POR gene can affect POR activity, CYP-mediated drug metabolism activities, and the efficacy of several clinically used drugs. The effects of POR variants on CYP activities are substrate dependent. In this review, recent research on the effects of POR genetic polymorphisms on drug metabolism and therapy has been summarized and discussed, which can contribute to the rational use of drugs in clinic and the development of personalized medicine.


Assuntos
Sistema Enzimático do Citocromo P-450/genética , Inativação Metabólica/genética , Polimorfismo Genético , Humanos , Mutação , Farmacogenética , Medicina de Precisão
6.
Oncotarget ; 8(69): 113828-113836, 2017 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-29371949

RESUMO

Peripheral nerve defects, but not artificial nerves, are repaired by endogenous cells. We examined cell activity during the repair process in the presence of autologous nerves and artificial preparations in order to guide future artificial nerve fabrication. PLGA tubes, nerve scaffolds comprising a PLGA tube plus 6,000 fibroin fibers, or autologous nerves were implanted into 10 mm rat sciatic nerve defects (n = 60 per group). Over a period of 1-20 weeks after nerve grafting, sections were stained and imaged to distinguish the cell types present and we quantified the recovery of motor and sensory function in the surgically implanted limb. We observed a decreasing trend in inflammatory cell and fibroblast counts over time which ranked in magnitude as: (PLGA group > nerve scaffold > autologous nerve> sham) and an opposite trend in Schwann cell counts. Differences in withdrawal time from hot water and static sciatic index (SSI) indicated that, after repair, sensory and motor function were best in the sham group, followed by the autologous group, the nerve scaffold group, and the PLGA group. These findings indicate that the inflammatory reaction is significant in the first two weeks after nerve grafting, followed by the rebirth of fibroblasts and Schwann cells, which guide axon regeneration. This inflammatory response was a fundamental stage of peripheral defect repair, but a weaker inflammatory response corresponded to better recovery of sensorimotor functional.

7.
Artigo em Inglês | MEDLINE | ID: mdl-27618077

RESUMO

Colorectal cancer (CRC) represents the third most common type of cancer in developed countries and one of the leading causes of cancer deaths worldwide. Personalized management of CRC has gained increasing attention since there are large inter-individual variations in the prognosis and response to drugs used to treat CRC owing to molecular heterogeneity. Approximately 15% of CRCs are caused by deficient mismatch repair (dMMR) characterized by microsatellite instability (MSI) phenotype. The present review is aimed at highlighting the role of MMR status in informing prognosis and personalized treatment of CRC including adjuvant chemotherapy, targeted therapy, and immune checkpoint inhibitor therapy to guide the individualized therapy of CRC.


Assuntos
Neoplasias Colorretais/genética , Reparo de Erro de Pareamento de DNA , Instabilidade de Microssatélites , Medicina de Precisão , Animais , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/tratamento farmacológico , Humanos , Prognóstico
8.
J Pharm Pharmacol ; 68(9): 1193-202, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27366899

RESUMO

OBJECTIVES: All-trans-retinoic acid (ATRA), a naturally occurring metabolite of vitamin A, has been shown to have great potential as an antitumorigenic drug to treat acute leukaemia by promoting cancer cell differentiation. Cytochrome P450 oxidoreductase (POR) is the only obligate electron donor for all of the microsomal cytochrome P450 enzymes including CYP26A1 which is highly specific for ATRA metabolism and efficacy in human myeloid leukaemia cells. In this study, we aimed to investigate the effect of POR on ATRA efficacy and CYP26A1 expression in human myeloid leukaemia HL-60 cells. METHODS: Stably expressed POR and POR-RNAi HL-60 cell lines were established by transfecting POR overexpression or RNAi (RNA interference) vectors mediated by lentivirus. The protein expression of POR and CYP26A1 was examined by Western blot. The potential roles of POR on ATRA efficacy in HL-60 cells were explored by cell viability assay, cell cycle distribution, cellular differentiation and apoptosis analysis. KEY FINDINGS: All-trans-retinoic acid treatment caused the expression of POR upregulation and CYP26A1 downregulation in dose- and time-dependent manners. POR overexpression decreased CYP26A1 expression in HL-60 cells. When POR gene was interfered, the downregulation of CYP26A1 expression by ATRA was abolished. In addition, POR overexpression in HL-60 cells significantly compromised ATRA-induced cell proliferation inhibition, cell cycle arrest, differentiation and apoptosis, whereas downregulation of POR significantly potentiated ATRA effects. CONCLUSIONS: Our study therefore suggested that POR played an important role in regulating ATRA efficacy and CYP26A1 expression in HL-60 cells.


Assuntos
Leucemia Mieloide/tratamento farmacológico , NADPH-Ferri-Hemoproteína Redutase/metabolismo , Ácido Retinoico 4 Hidroxilase/metabolismo , Tretinoína/metabolismo , Apoptose , Pontos de Checagem do Ciclo Celular , Diferenciação Celular , Proliferação de Células , Sistema Enzimático do Citocromo P-450/metabolismo , Células HL-60 , Humanos , Inativação Metabólica , Tretinoína/farmacocinética , Tretinoína/farmacologia , Tretinoína/uso terapêutico
9.
J Theor Biol ; 400: 1-10, 2016 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-27084358

RESUMO

Protein structural class prediction plays an important role in protein structure and function analysis, drug design and many other biological applications. Extracting good representation from protein sequence is fundamental for this prediction task. In recent years, although several secondary structure based feature extraction strategies have been specially proposed for low-similarity protein sequences, the prediction accuracy still remains limited. To explore the potential of secondary structure information, this study proposed a novel feature extraction method from the chaos game representation of predicted secondary structure to mainly capture sequence order information and secondary structure segments distribution information in a given protein sequence. Several kinds of prediction accuracies obtained by the jackknife test are reported on three widely used low-similarity benchmark datasets (25PDB, 1189 and 640). Compared with the state-of-the-art prediction methods, the proposed method achieves the highest overall accuracies on all the three datasets. The experimental results confirm that the proposed feature extraction method is effective for accurate prediction of protein structural class. Moreover, it is anticipated that the proposed method could be extended to other graphical representations of protein sequence and be helpful in future research.


Assuntos
Algoritmos , Biologia Computacional/métodos , Estrutura Secundária de Proteína , Proteínas/química , Bases de Dados de Proteínas , Reprodutibilidade dos Testes , Máquina de Vetores de Suporte
10.
Pharmacogenet Genomics ; 26(2): 80-7, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26580670

RESUMO

BACKGROUND/AIM: Cytochrome P450 oxidoreductase (POR) is required for drug metabolism by all microsomal cytochrome P450 (CYP) enzymes. The aim of this study was to investigate whether single-nucleotide polymorphisms in the POR gene were correlated with interindividual variations in CYP2B6 activity, as measured by bupropion hydroxylation. METHODS: Thirty-five healthy individuals with selected CYP2B6 and POR polymorphisms were involved in the clinical study. The activity of CYP2B6 was evaluated on the basis of the area under the time-concentration curve (AUC) ratio of hydroxybupropion versus bupropion (AUC_hyd/AUC_bup). RESULTS: Individuals carrying CYP2B6*1/*1 showed a significantly higher mean AUC_hyd/AUC_bup than individuals carrying the CYP2B6*1/*6 and CYP2B6*6/*6 variants (17.1 ± 6.23 vs. 10.3 ± 4.53, P = 0.003 and 17.1 ± 6.23 vs. 9.41 ± 2.84, P = 0.002, respectively). POR g.6593A>G (rs2868177) AA homozygotes showed a significantly lower mean AUC_hyd/AUC_bup than POR g.6593A>G AG heterozygotes or GG homozygotes (8.54 ± 2.65 vs. 14.9 ± 6.06, P = 0.005 and 8.54 ± 2.65 vs. 16.8 ± 6.45, P = 0.002, respectively). Moreover, POR g.6593A>G AA homozygotes had a significantly lower mean AUC_hyd/AUC_bup than the POR g.6593A>G AG/GG genotypes in the CYP2B6*1/*1, CYP2B6*1/*6 and CYP2B6*6/*6 groups (10.9 ± 1.82 vs. 19.7 ± 5.53, P < 0.001; 6.18 ± 0.284 vs. 12.1 ± 4.31, P = 0.011; and 6.94 ± 1.48 vs. 10.9 ± 2.39, P = 0.043, respectively). There was no significant difference in the mean AUC_hyd/AUC_bup among different POR c.1508C>T (*28 or rs1057868) genotypes, even after the effect of CYP2B6*6 was excluded. CONCLUSION: These results indicate, for the first time, that the POR g.6593A>G polymorphism significantly influences CYP2B6 activity, as measured by bupropion hydroxylation, in humans, and the CYP2B6*6 and POR g.6593A>G polymorphisms might be considered simultaneously for the individualized therapy with CYP2B6 substrate drugs such as bupropion.


Assuntos
Bupropiona/metabolismo , Citocromo P-450 CYP2B6/genética , Sistema Enzimático do Citocromo P-450/genética , NADPH-Ferri-Hemoproteína Redutase/metabolismo , Polimorfismo Genético , Humanos , Hidroxilação , NADPH-Ferri-Hemoproteína Redutase/genética
11.
Cancer Chemother Pharmacol ; 77(4): 673-84, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26707728

RESUMO

Epigenetics, referring to alterations in gene expression without a change in nucleotide sequence in eukaryotes, mainly includes DNA methylation, miRNA and histone modification. In recent years, accumulating evidences have shown that epigenetic aberrations not only play important roles in the initiation and development of human cancers but also affect cancer chemotherapy response by altering the expression of key genes involved in the absorption, distribution, metabolism and excretion of drugs or those correlated with progression or severity of cancers. These epigenetic alterations, along with advanced detecting techniques, have great potential to be used as predictive and prognostic biomarkers for personalized therapy, especially in the field of cancer treatment. Here we provide an overview of recent findings on epigenetic alterations involved in cancer chemotherapy response, with the aim of promoting rational use of chemotherapy drugs in the clinic.


Assuntos
Epigênese Genética , Neoplasias/tratamento farmacológico , Acetilação , Antineoplásicos/uso terapêutico , Metilação de DNA , Histonas/metabolismo , Humanos , MicroRNAs/fisiologia , Neoplasias/genética , Polimorfismo de Nucleotídeo Único
12.
Yi Chuan ; 36(10): 1006-12, 2014 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-25406248

RESUMO

The varnished eye (ve) mutant is one of the rare natural recessive mutants related to the abnormal phenotypes in the compound eye of silkworm (Bombyx mori). The compound eyes of the ve adults are smaller and glossier than those of the wild-type Dazao (Dz) and many tumor-like bumps are present on their surface; their small eyes are irregularly arranged and are smaller and fewer than those of the wild-type. The mutant gene ve has been located at the 32.2 locus of chromosome 6 in the classic genetic linkage map. However, it still remains unknown about the mechanism responsible for the mutant. In this study, we got a BC1 generation using male F1 (ve×Dz) with female ve for fine mapping of this mutant gene. The results showed that ve was located in a region between SNP3 and SNP6. The physical distance is approximately 1.2 Mb in the low density linkage map. By constructing a high-density map using 1563 BC1 individuals, the ve mutant gene was further mapped into a region between the SNP5 and SNP61. The physical region is about 221.8 kb and contains six potential genes but no specific mutations were found in the CDSs of these candidate genes. RT-PCR showed that the expression of BGIBMGA013642 was decreased obviously compared with that in wild type, suggesting it might be a key candidate gene for further studying the ve mutant.


Assuntos
Bombyx/genética , Mapeamento Cromossômico , Anormalidades do Olho/genética , Mutação , Animais , Clonagem Molecular , Feminino , Ligação Genética , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único/genética
13.
Cancer Chemother Pharmacol ; 74(2): 217-27, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24889719

RESUMO

Pregnane X receptor (PXR) is a member of the nuclear receptor superfamily that differently expresses not only in human normal tissues but also in numerous types of human cancers. PXR can be activated by many endogenous substances and exogenous chemicals, and thus affects chemotherapeutic effects and intervenes drug-drug interactions by regulating its target genes involving drug metabolism and transportation, cell proliferation and apoptosis, and modulating endobiotic homeostasis. Tissue and context-specific regulation of PXR contributes to diverse effects in the treatment for numerous cancers. Genetic variants of PXR lead to intra- and inter-individual differences in the expression and inducibility of PXR, resulting in different responses to chemotherapy in PXR-positive cancers. The purpose of this review is to summarize and discuss the role of PXR in the metabolism and clearance of anticancer drugs. It is also expected that this review will provide insights into PXR-mediated enhancement for chemotherapeutic treatment, prediction of drug-drug interactions and personalized medicine.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Receptores de Esteroides/metabolismo , Animais , Humanos , Receptor de Pregnano X
14.
J Theor Biol ; 344: 12-8, 2014 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-24316044

RESUMO

Extracting good representation from protein sequence is fundamental for protein structural classes prediction tasks. In this paper, we propose a novel and powerful method to predict protein structural classes based on the predicted secondary structure information. At the feature extraction stage, a 13-dimensional feature vector is extracted to characterize general contents and spatial arrangements of the secondary structural elements of a given protein sequence. Specially, four segment-level features are designed to elevate discriminative ability for proteins from the α/ß and α+ß classes. After the features are extracted, a multi-class non-linear support vector machine classifier is used to implement protein structural classes prediction. We report extensive experiments comparing the proposed method to the state-of-the-art in protein structural classes prediction on three widely used low-similarity benchmark datasets: FC699, 1189 and 640. Our method achieves competitive performance on prediction accuracies, especially for the overall prediction accuracies which have exceeded the best reported results on all of the three datasets.


Assuntos
Aminoácidos/química , Estrutura Secundária de Proteína , Análise de Sequência de Proteína/métodos , Algoritmos , Sequência de Aminoácidos , Animais , Bases de Dados de Proteínas , Conformação Proteica , Homologia de Sequência de Aminoácidos , Máquina de Vetores de Suporte
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