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1.
Environ Microbiol ; 22(4): 1507-1516, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31215728

RESUMO

Successful application of microorganisms to heavy metal remediation depends on their resistance to toxic metals. This study contrasted the differences of tolerant mechanisms between Pb2+ and Cd2+ in Enterobacter sp. Microbial respiration and production of formic acid showed that Enterobacter sp. had a higher tolerant concentration of Pb (>1000 mg l-1 ) than Cd (about 200 mg l-1 ). Additionally, SEM confirmed that most of Pb and Cd nanoparticles (NPs) were adsorbed onto cell membrane. The Cd stress, even at low concentration (50 mg l-1 ), significantly enlarged the sizes of cells. The cellular size raised from 0.4 × 1.0 to 0.9 × 1.6 µm on average, inducing a platelet-like shape. In contrast, Pb cations did not stimulate such enlargement even up to 1000 mg l-1 . Moreover, Cd NPs were adsorbed homogeneously by almost all the bacterial cells under TEM. However, only a few cells work as 'hot spots' on the sorption of Pb NPs. The heterogeneous sorption might result from a 'self-sacrifice' mechanism, i.e., some cells at a special life stage contributed mostly to Pb sorption. This mechanism, together with the lower mobility of Pb cations, caused higher microbial tolerance and removal efficiency towards Pb2+ . This study sheds evident contrasts of bacterial resistance to the two most common heavy metals.


Assuntos
Cádmio/toxicidade , Enterobacter/efeitos dos fármacos , Chumbo/toxicidade , Nanopartículas Metálicas/toxicidade , Adsorção , Cádmio/química , Membrana Celular/química , Tamanho Celular/efeitos dos fármacos , Enterobacter/química , Enterobacter/metabolismo , Enterobacter/ultraestrutura , Formiatos/metabolismo , Chumbo/química , Nanopartículas Metálicas/química , Microscopia Eletrônica de Transmissão , Estresse Fisiológico
2.
Ecotoxicol Environ Saf ; 194: 110441, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32155484

RESUMO

Vesicles (Ves) within fungal cells are the critical linkage between intracellular and extracellular systems. This study explored the application of Pb2+ to probe the physiology of intracellular Ves in Rhodotorula mucilaginosa (Rho). At low Pb2+ levels (0-500 mg/L), there was no evident change in the content of extracellular polymeric substances (EPS) or microbial activity. At medium-high levels (1000-2000 mg/L), the sizes of Ves within the Rho cells were significantly enlarged, with abundant lead nano-particles (Pb NPs) formed either on the cell surface or interior, whereas the EPS content and bioactivity were still stable. At a high level (2500 mg/L), the Rho cells were severely deformed, with cell counts reduced by more than 99%. However, the EPS contents and the respiration rate of the surviving cells dramatically increased to the maximum values (i.e., 1785 mg/1010 cells and 37 mg C 10-10 cells h-1, respectively). The Ves surface adsorbed Pb cations with higher density, compared with the cell membrane. Moreover, fusion of some Ves to the membrane (functioning in transport) was observed under transmission electron microscope (TEM). Three pathways of detoxification via intracellular Ves were finally proposed, i.e., Ve-mediated transport (from intracellular to extracellular) of EPS components, absorption of Pb NPs on the Ve surface, and accumulation of Pb NPs within Ves. This study sheds light on the possibility of exploring microbial physiology via Pb2+ cations.


Assuntos
Substâncias Perigosas/toxicidade , Chumbo/toxicidade , Rhodotorula/fisiologia , Adsorção , Cátions , Testes de Toxicidade
3.
J Med Internet Res ; 21(5): e12522, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-31045507

RESUMO

BACKGROUND: As the quality of online health information remains questionable, there is a pressing need to understand how consumers evaluate this information. Past reviews identified content-, source-, and individual-related factors that influence consumer judgment in this area. However, systematic knowledge concerning the evaluation process, that is, why and how these factors influence the evaluation behavior, is lacking. OBJECTIVE: This review aims (1) to identify criteria (rules that reflect notions of value and worth) that consumers use to evaluate the quality of online health information and the indicators (properties of information objects to which criteria are applied to form judgments) they use to support the evaluation in order to achieve a better understanding of the process of information quality evaluation and (2) to explicate the relationship between indicators and criteria to provide clear guidelines for designers of consumer health information systems. METHODS: A systematic literature search was performed in seven digital reference databases including Medicine, Psychology, Communication, and Library and Information Science to identify empirical studies that report how consumers directly and explicitly describe their evaluation of online health information quality. Thirty-seven articles met the inclusion criteria. A qualitative content analysis was performed to identify quality evaluation criteria, indicators, and their relationships. RESULTS: We identified 25 criteria and 165 indicators. The most widely reported criteria used by consumers were trustworthiness, expertise, and objectivity. The indicators were related to source, content, and design. Among them, 114 were positive indicators (entailing positive quality judgments), 35 were negative indicators (entailing negative judgments), and 16 indicators had both positive and negative quality influence, depending on contextual factors (eg, source and individual differences) and criteria applied. The most widely reported indicators were site owners/sponsors; consensus among multiple sources; characteristics of writing and language; advertisements; content authorship; and interface design. CONCLUSIONS: Consumer evaluation of online health information is a complex cost-benefit analysis process that involves the use of a wide range of criteria and a much wider range of quality indicators. There are commonalities in the use of criteria across user groups and source types, but the differences are hard to ignore. Evidently, consumers' health information evaluation can be characterized as highly subjective and contextualized, and sometimes, misinformed. These findings invite more research into how different user groups evaluate different types of online sources and a personalized approach to educate users about evaluating online health information quality.


Assuntos
Informação de Saúde ao Consumidor/métodos , Informática Médica/métodos , Garantia da Qualidade dos Cuidados de Saúde/métodos , Comunicação , Humanos , Internet
4.
J Hazard Mater ; 426: 127984, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-34953259

RESUMO

The coexistence of heavy metals in aquatic systems causes complex toxicity in microorganisms. In this study, we explored the influences of Pb2+ addition on Cd2+ toxicity in Rhodotorula mucilaginosa (Rho). Cd toxicity alone was tested with up to 200 mg/L Cd2+ to induce stress. Cell counts and Cd2+ removal rates declined to a minimum when the Cd2+ concentration reached 150 mg/L, confirming strong Cd-induced toxicity. Then, co-existence of Pb2+ and Cd2+ was established as Pb-CdH (Pb/Cd = 1, molar ratio), Pb-CdM (Pb/Cd = 10), and Pb-CdL (Pb/Cd = 100). The Pb-CdL and Pb-CdM treatments showed clear similarities in terms of their effects on cell counts, polysaccharide concentrations, and cell morphology. There was also no significant difference in their gene expression profiles. The competition between the two types of cations caused preferential extra/intracellular sorption of less toxic Pb2+. Moreover, the expression of genes related to glycolysis, the TCA cycle, and oxidative phosphorylation was significantly enhanced in the cells with Pb-CdH treatment, suggesting that these cells were functional. Furthermore, the excitability-caused increase in the cell count after Pb-CdH treatment (Cd2+ = 112.4 mg/L) was 30% higher than that of the 100 mg/L Cd2+ treatment. These results proved that the addition of Pb2+ in solution significantly weakened the toxicity of Cd2+.


Assuntos
Cádmio , Metais Pesados , Cádmio/toxicidade , Fungos , Chumbo/toxicidade
5.
Addict Behav ; 114: 106699, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33268185

RESUMO

With the increasing use of social media, the addictive use of this new technology also grows. Previous studies found that addictive social media use is associated with negative consequences such as reduced productivity, unhealthy social relationships, and reduced life-satisfaction. However, a holistic theoretical understanding of how social media addiction develops is still lacking, which impedes practical research that aims at designing educational and other intervention programs to prevent social media addiction. In this study, we reviewed 25 distinct theories/models that guided the research design of 55 empirical studies of social media addiction to identify theoretical perspectives and constructs that have been examined to explain the development of social media addiction. Limitations of the existing theoretical frameworks were identified, and future research areas are proposed.


Assuntos
Comportamento Aditivo , Mídias Sociais , Humanos , Internet , Transtorno de Adição à Internet , Relações Interpessoais
6.
Genes (Basel) ; 12(12)2021 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-34946960

RESUMO

Members of AP1/FUL subfamily genes play an essential role in the regulation of floral meristem transition, floral organ identity, and fruit ripping. At present, there have been insufficient studies to explain the function of the AP1/FUL-like subfamily genes in Asteraceae. Here, we cloned two euAP1 clade genes TeAP1-1 and TeAP1-2, and three euFUL clade genes TeFUL1, TeFUL2, and TeFUL3 from marigold (Tagetes erecta L.). Expression profile analysis demonstrated that TeAP1-1 and TeAP1-2 were mainly expressed in receptacles, sepals, petals, and ovules. TeFUL1 and TeFUL3 were expressed in flower buds, stems, and leaves, as well as reproductive tissues, while TeFUL2 was mainly expressed in flower buds and vegetative tissues. Overexpression of TeAP1-2 or TeFUL2 in Arabidopsis resulted in early flowering, implying that these two genes might regulate the floral transition. Yeast two-hybrid analysis indicated that TeAP1/FUL proteins only interacted with TeSEP proteins to form heterodimers and that TeFUL2 could also form a homodimer. In general, TeAP1-1 and TeAP1-2 might play a conserved role in regulating sepal and petal identity, similar to the functions of MADS-box class A genes, while TeFUL genes might display divergent functions. This study provides a theoretical basis for the study of AP1/FUL-like genes in Asteraceae species.


Assuntos
Clonagem Molecular/métodos , Perfilação da Expressão Gênica/métodos , Proteínas de Domínio MADS/genética , Tagetes/crescimento & desenvolvimento , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Evolução Molecular , Flores/genética , Regulação da Expressão Gênica de Plantas , Filogenia , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Tagetes/genética , Tagetes/metabolismo , Técnicas do Sistema de Duplo-Híbrido
7.
Microsc Res Tech ; 84(11): 2784-2806, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33988282

RESUMO

Microlenses have become an indispensable optical element in many optical systems. The advancement of technology has led to a wider variety of microlenses fabrication methods, but these methods suffer from, more or less, some limitations. In this article, we review the manufacturing technology of microlenses from the direct and indirect perspectives. First, we present several fabrication methods and their advantages and disadvantages are discussed. Then, we discuss the commonly used materials for fabricating microlenses and the applications of microlenses in various fields. Finally, we point out the prospects for the future development of microlenses and their fabrication methods.

8.
PLoS One ; 16(7): e0249825, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34228738

RESUMO

The water dropworts Oenanthe linearis Wall. ex DC. and O. javanica (Blume) DC. are aquatic perennial herbs that have been used in China as vegetables and traditional medicines. However, their phylogenetic relationships and genetic diversity are poorly understood. Here, we presented the phenotypic traits and genome-wide DNA marker-based analysis of 158 water dropwort accessions representing both species. The analysis revealed that Oenanthe linearis was readily segregated into linear-leaf and deep-cleft leaf water dropworts according to their leaf shapes at flowering. Oenanthe javanica was classified by clustering analysis into two clusters based mainly on the morphological characteristics of their ultimate segments (leaflets). A set of 11 493 high-quality single-nucleotide polymorphisms was identified and used to construct a phylogenetic tree. There was strong discrimination between O. linearis and O. javanica, which was consistent with their phenotype diversification. The population structure and phylogenetic tree analyses suggested that the O. linearis accessions formed two major groups, corresponding to the linear-leaf and deep-cleft leaf types. The most obvious phenotypic differences between them were fully expressed at the reproductive growth stage. A single-nucleotide polymorphism-based analysis revealed that the O. javanica accessions could be categorized into groups I andII. However, this finding did not entirely align with the clusters revealed by morphological classification. Landraces were clustered into one group along with the remaining wild accessions. Hence, water dropwort domestication was short in duration. The level of genetic diversity for O. linearis (π = 0.1902) was slightly lower than that which was estimated for O. javanica (π = 0.2174). There was a low level of genetic differentiation between O. linearis and O. javanica (Fst = 0.0471). The mean genetic diversity among accessions ranged from 0.1818 for the linear-leaf types to 0.2318 for the groupII accessions. The phenotypic traits and the single-nucleotide polymorphism markers identified here lay empirical foundation for future genomic studies on water dropwort.


Assuntos
Oenanthe/genética , Filogenia , Polimorfismo de Nucleotídeo Único , Marcadores Genéticos
9.
Br J Clin Pharmacol ; 69(1): 67-73, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20078614

RESUMO

UNLABELLED: WHAT IS ALREADY KNOWN ABOUT THE SUBJECT: * Concomitant use of different drugs may yield excessive risk for adverse drug reactions and it is a challenging task to do surveillance on the safety profile of the interaction between different drugs. * Currently, several methods are used by pharmacoepidemiologists and statisticians to detect possible drug-drug interactions in spontaneous reporting systems. * However, with the increasing number of reports in the system, there is a growing need for a computerized system that could facilitate the process of data arrangement and detection of drug interaction. WHAT THIS STUDY ADDS: * We had already developed a computerized system to detect adverse drug reaction signals due to single drugs. * After the development of this system, interaction between different drugs could also be detected automatically and intelligently. AIMS: In spontaneous reporting systems (SRS), there is a growing need for the automated detection of adverse drug reactions (ADRs) resulting from drug-drug interactions. In addition, special attention is also needed for systems facilitating automated data preprocessing. In our study, we set up a computerized system to signal possible drug-drug interactions by which data acquisition and signal detection could be carried out automatically and the process of data preprocessing could also be facilitated. METHODS: This system was developed with Microsoft Visual Basic 6.0 and Microsoft Access was used as the database. Crude ADR reports submitted to Shanghai SRS from January 2007 to December 2008 were included in this study. The logistic regression method, the Omega shrinkage measure method, an additive model and a multiplicative model were used for automatic detection of drug-drug interactions where two drugs were used concomitantly. RESULTS: A total of 33 897 crude ADR reports were acquired from the SRS automatically. The 10 drug combinations most frequently reported were found and the 10 most suspicious drug-drug ADR combinations for each method were detected automatically after the performance of the system. CONCLUSIONS: Since the detection of drug-drug interaction depends upon the skills and memory of the professionals involved, is time consuming and the number of reports is increasing, this system might be a promising tool for the automated detection of possible drug-drug interactions in SRS.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/organização & administração , Bases de Dados Factuais , Sistemas Computadorizados de Registros Médicos/organização & administração , Algoritmos , Interações Medicamentosas , Modelos Estatísticos
10.
PeerJ ; 8: e10485, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33354429

RESUMO

Taro (Colocasia esculenta) is an important root and tuber crop cultivated worldwide. There are two main types of taro that vary in morphology of corm and cormel, 'dasheen' and 'eddoe'. The eddoe type (Colocasia esculenta var. antiquorium) is predominantly distributed throughout China. Characterizing the genetic diversity present in the germplasm bank of taro is fundamental to better manage, conserve and utilize the genetic resources of this species. In this study, the genetic diversity of 234 taro accessions from 16 provinces of China was assessed using 132,869 single nucleotide polymorphism (SNP) markers identified by specific length amplified fragment-sequencing (SLAF-seq). Population structure and principal component analysis permitted the accessions to be categorized into eight groups. The genetic diversity and population differentiation of the eight groups were evaluated using the characterized SNPs. Analysis of molecular variance showed that the variation among eight inferred groups was higher than that within groups, while a relatively small variance was found among the two morphological types and 16 collection regions. Further, a core germplasm set comprising 41 taro accessions that maintained the genetic diversity of the entire collection was developed based on the genotype. This research is expected to be valuable for genetic characterization, germplasm conservation, and breeding of taro.

11.
Mol Cell Biol ; 40(14)2020 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-32341082

RESUMO

Pathological cardiac hypertrophy is driven by neurohormonal activation of specific G protein-coupled receptors (GPCRs) in cardiomyocytes and is accompanied by large-scale changes in cardiomyocyte gene expression. These transcriptional changes require activity of positive transcription elongation factor b (P-TEFb), which is recruited to target genes by the bromodomain protein Brd4 or the super elongation complex (SEC). Here, we describe GPCR-specific regulation of these P-TEFb complexes and a novel mechanism for activating Brd4 in primary neonatal rat cardiomyocytes. The SEC was required for the hypertrophic response downstream of either the α1-adrenergic receptor (α1-AR) or the endothelin receptor (ETR). In contrast, Brd4 inhibition selectively impaired the α1-AR response. This was corroborated by the finding that the activation of α1-AR, but not ETR, increased Brd4 occupancy at promoters and superenhancers of hypertrophic genes. Transcriptome analysis demonstrated that the activation of both receptors initiated similar gene expression programs, but that Brd4 inhibition attenuated hypertrophic genes more robustly following α1-AR activation. Finally, we show that protein kinase A (PKA) is required for α1-AR stimulation of Brd4 chromatin occupancy. The differential role of the Brd4/P-TEFb complex in response to distinct GPCR pathways has potential clinical implications, as therapies targeting this complex are currently being explored for heart failure.


Assuntos
Cardiomegalia/metabolismo , Quinase 9 Dependente de Ciclina/metabolismo , Miócitos Cardíacos/metabolismo , Fator B de Elongação Transcricional Positiva/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animais , Cardiomegalia/patologia , Células Cultivadas , Miócitos Cardíacos/patologia , Proteínas Nucleares/metabolismo , Subunidades Proteicas/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Adrenérgicos alfa 1/metabolismo , Receptores de Endotelina/metabolismo , Fatores de Transcrição/metabolismo
12.
Nanoscale ; 12(9): 5380-5396, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32022069

RESUMO

9-Nitro-20(S)-camptothecin (9-NC) is a broad-spectrum antitumor drug used in tumor treatments, but its clinical applications and antitumor efficacy are limited by its structural instability, poor solubility, and extremely low drug utilization in tumor tissues. In this study, enzyme-sensitive nuclear-targeted dual-functional polymeric micelles were developed for 9-NC delivery with a high drug loading content (12.93 ± 0.88%), steady-state circulation, and a rapid attack at the "heart" of tumor cells. Briefly, chrysin (CHR) as a π-conjugated moiety was immobilized on the PCL terminal in the TAT-PCL amphiphiles and combined with the ALAL peptide as a linker on HA chains to yield the ultimate CHR-PCL-TAT-ALAL-HA (HATPC) amphiphiles. Spherical 9-NC-loaded micelles were obtained from the self-assembly of the dual-functional amphiphiles comprising HATPC and 9-NC with uniform nanosize (121.6 ± 5.79 nm), well-distributed morphology (PDI: 0.256), and negative surface charge (-23.2 ± 0.5 mV), yielding high stability during blood circulation. In this drug delivery system, HA acts as an active tumor-targeting instrument via CD44-receptor-mediated endocytosis; further, the ALAL peptide could be cutoff in the lysosomes of the tumor cells due to the high expression of cathepsin B, leading to lysosomal escape, while the secondary polymeric micelles targeted the tumor cell nucleus via the exposed TAT peptide. The enzyme sensitivity and nuclei targetability of the 9-NC/HATPC micelles were confirmed by dynamic light scattering and confocal laser scanning microscopy analyses. As compared to free 9-NC and traditional mPEG2k-PCL2k polymeric micelles, 9-NC/HATPC micelles were the most concentrated in the tumor cell nucleus; therefore, they exhibited the highest cytotoxicity against SKOV3 tumor cells both in vitro (IC50 = 0.03 µg mL-1) and in vivo. This enzyme-sensitive nuclear-targeted dual-functional drug delivery system involving HATPC provided a new and promising strategy for enhanced 9-NC delivery and antitumor efficacy.


Assuntos
Antineoplásicos Fitogênicos/química , Camptotecina/química , Portadores de Fármacos/química , Micelas , Polímeros/química , Animais , Antineoplásicos Fitogênicos/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Camptotecina/metabolismo , Camptotecina/farmacologia , Camptotecina/uso terapêutico , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/síntese química , Humanos , Camundongos , Camundongos Nus , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Tamanho da Partícula , Peptídeos/química , Peptídeos/metabolismo , Transplante Heterólogo
13.
Artif Cells Nanomed Biotechnol ; 48(1): 525-532, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32037890

RESUMO

Here we presented a novel micelle self-assembled from amphiphiles with π-conjugated moieties (OEG-DPH). The π-conjugated structural integrity of the micelles enabled stable encapsulation of Nile Red (NR, model drug). The self-assembly behaviour of the amphiphiles and the release profile of NR loaded micelles were investigated. Spherical core-shell structured NR loaded micelles with low CMC of 57 µg/mL and the efficient intracellular delivery process was monitored. This research provided a way to fabricate stable polymeric micelles and develop a practical nanocarrier for therapeutics delivery.


Assuntos
Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Micelas , Portadores de Fármacos/síntese química , Liberação Controlada de Fármacos , Células HeLa , Humanos , Hidrazonas/química , Oxazinas/química , Oxazinas/farmacocinética , Polímeros/síntese química , Polímeros/química
14.
Pharmacoepidemiol Drug Saf ; 18(2): 154-8, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19115240

RESUMO

PURPOSE: We developed a computerized system for signal detection in spontaneous reporting system (SRS) of Shanghai. Data acquisition, data mining could be carried out automatically and the process of data preprocessing and cleaning could be facilitated. This system was expected to detect signals from SRS after drug licensing with minimum patient exposure. METHODS: This system was developed by Microsoft visual basic (VB) 6.0. Data preprocessing, data cleaning, and data mining were based upon visual basic for application (VBA) in Microsoft Excel 2003. Database of drug generic name and adverse drug reaction (ADR) standard dictionary were set up initially for data cleaning and coding. Algorithms including reporting odds ratio (ROR), proportional reporting ratio (PRR), measure used by the Medicines and Healthcare Products Regulatory Agency (MHRA), Bayesian confidence propagation neural network (BCPNN) were employed in this system. Crude ADR reports submitted to Shanghai ADR SRS from December 2003 to April 2007 were used as a material in this study to test the feasibility and flexibility of this system. RESULTS: Thirty two thousand seven hundred and fourty six crude ADR reports were acquired from the SRS automatically. Two thousand one hundred and fourty seven drug generic name and 621 ADR name were kept in the database after data preprocessing and cleaning. A total of 1430, 1419, 868 and 997 possible drug-ADR signals were generated by ROR, PRR, BCPNN and MHRA, respectively. CONCLUSIONS: The results indicate that this computerized system is a flexible one that can help to detect possible drug-ADR signals intelligently in SRS of Shanghai now. It is a promising system for post-marketing surveillance on both chemical medicine and Chinese traditional medicine.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/organização & administração , Bases de Dados Factuais , Sistemas Computadorizados de Registros Médicos/organização & administração , Redes Neurais de Computação , Algoritmos , Teorema de Bayes , China
15.
Pharmacoepidemiol Drug Saf ; 18(5): 357-61, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19253921

RESUMO

PURPOSE: To give an overview of the current status including problems and efforts about pharmacovigilance in Traditional Chinese Medicine (TCM) safety surveillance. METHODS: It is based on literature review and publicly available data in China. RESULTS: TCM led to several adverse drug reactions (ADRs) during the past few years and pharmacovigilance about TCM remained as a problem though great effort had been made to improve it. CONCLUSIONS: Pharmacovigilance in TCM is still facing many challenges in playing critical roles in China. More attention should be paid to pharmacovigilance in TCM safety surveillance.


Assuntos
Medicina Tradicional Chinesa/efeitos adversos , China , Humanos , Segurança , Fatores de Tempo
16.
J Biomed Nanotechnol ; 15(8): 1673-1687, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31219020

RESUMO

Prodrug self-assembled nanomedicines with cleavable moieties sensitive to intracellular stimuli have attracted great interest to pharmacists. In this paper, a docetaxel-hyaluronic acid (DTX-HA) conjugate with peptide, hydrazone bonds and disulfide in sequence, which were cleavable catalyzed by metalloproteinase (MMP), weak acidity and glutathione (GSH), respectively, were involved in a moiety as the linker to immobilize DTX on HA chains, the prodrugs were self-assembled into nanoparticles and utilized for cancer chemotherapy. The synthesis of conjugate was characterized by 1H NMR, ESI-TOF and GPC. The self-assembly of the conjugates was investigated via DLS and TEM. The release profiles revealed that the nanomedicine was disassociated to trigger the drug release in the simulated intracellular conditions of MMP, pH value and GSH, respectively. The in vitro anticancer activity of the nanomedicine with IC50 test, cytometry and confocal laser scanning microscopy exhibited efficient cellular uptake and apoptosis of cancer cells. The in vivo anticancer study of the nanomedicine in tumor-bearing nude mice showed promising therapeutic efficacy in magnificent inhibition tumor growth, long circulation time in pharmacokinetic and low toxicity to organs.


Assuntos
Nanomedicina , Animais , Linhagem Celular Tumoral , Glutationa , Concentração de Íons de Hidrogênio , Metaloproteases , Camundongos , Camundongos Nus , Pró-Fármacos
18.
Artif Cells Nanomed Biotechnol ; 46(sup1): 817-830, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29405791

RESUMO

Although it's pharmacological effect for cancer therapy, conventional chemotherapy has been compromised by a series of shortcomings such as limited stability, nonspecific tumour targeting ability and severe toxic side effects. To overcome these limitations, multifunctional targeted drug delivery systems for combinatorial therapeutics have been widely explored as novel cancer therapy strategies, showing encouraging results in many pre-clinical animal experiments. Among them, synergistic phototherapy and chemotherapy have demonstrated their abilities to enhance therapeutic efficacies and reduce unwanted side effects via a variety of mechanisms. In this review, we will summarize the latest progress in the development of targeted drug delivery systems with combinations of phototherapy and chemotherapy and discuss the important roles of phototherapy agents involved in those non-conventional therapeutic strategies.


Assuntos
Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Neoplasias/terapia , Fototerapia , Animais , Terapia Combinada , Humanos , Neoplasias/tratamento farmacológico
19.
Cell Signal ; 44: 43-50, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29329779

RESUMO

The signalling functions of many G protein-coupled receptors (GPCRs) expressed in the myocardium are incompletely understood. Among these are the endothelin receptor (ETR) family and α1-adrenergic receptor (α1-AR), which are thought to couple to the G protein Gαq. In this study, we used transcriptome analysis to compare the signalling networks downstream of these receptors in primary neonatal rat cardiomyocytes. This analysis indicated increased expression of target genes of cAMP responsive element modulator (CREM) after 24 h treatment with the α1-AR agonist phenylephrine, but not the ETR agonist endothelin-1, suggesting a specific role for the α1-AR in promoting cAMP production in cardiomyocytes. To validate the difference observed between these two GPCRs, we used heterologous expression of the receptors and genetically encoded biosensors in HEK 293 cell lines. We validated that both α1A- and α1B-AR subtypes were able to lead to the accumulation of cAMP in response to phenylephrine in both the nucleus and cytoplasm in a Gαs-dependent manner. However, the ETR subtype ETA did not affect cAMP levels in either compartment. All three receptors were coupled to Gαq signalling as expected. Further, we showed that activation of PKA in different compartments was α1-AR subtype specific, with α1B-AR able to activate PKA in the cytoplasm and nucleus and α1A-AR only able to in the nucleus. We provide evidence for a pathway downstream of the α1-AR, and show that distinct pools of a receptor lead to differential activation of downstream effector proteins dependent on their cellular compartment.


Assuntos
Modulador de Elemento de Resposta do AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Miócitos Cardíacos/citologia , Receptor de Endotelina A/fisiologia , Receptores Adrenérgicos alfa 1/fisiologia , Agonistas de Receptores Adrenérgicos alfa 1/farmacologia , Animais , Células HEK293 , Humanos , Fenilefrina/farmacologia , Ratos
20.
PLoS One ; 12(1): e0169777, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28081202

RESUMO

According to the floral organ development ABC model, B class genes specify petal and stamen identification. In order to study the function of B class genes in flower development of Tagetes erecta, five MADS-box B class genes were identified and their expression and putative functions were studied. Sequence comparisons and phylogenetic analyses indicated that there were one PI-like gene-TePI, two euAP3-like genes-TeAP3-1 and TeAP3-2, and two TM6-like genes-TeTM6-1 and TeTM6-2 in T. erecta. Strong expression levels of these genes were detected in stamens of the disk florets, but little or no expression was detected in bracts, receptacles or vegetative organs. Yeast hybrid experiments of the B class proteins showed that TePI protein could form a homodimer and heterodimers with all the other four B class proteins TeAP3-1, TeAP3-2, TeTM6-1 and TeTM6-2. No homodimer or interaction was observed between the euAP3 and TM6 clade members. Over-expression of five B class genes of T. erecta in Nicotiana rotundifolia showed that only the transgenic plants of 35S::TePI showed altered floral morphology compared with the non-transgenic line. This study could contribute to the understanding of the function of B class genes in flower development of T. erecta, and provide a theoretical basis for further research to change floral organ structures and create new materials for plant breeding.


Assuntos
Proteínas de Domínio MADS/genética , Proteínas de Plantas/genética , Tagetes/genética , Sequência de Aminoácidos , Dimerização , Flores/genética , Flores/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Domínio MADS/classificação , Proteínas de Domínio MADS/metabolismo , Dados de Sequência Molecular , Fenótipo , Filogenia , Proteínas de Plantas/classificação , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA de Plantas/genética , RNA de Plantas/isolamento & purificação , RNA de Plantas/metabolismo , Alinhamento de Sequência , Tagetes/classificação , Tagetes/crescimento & desenvolvimento , Tagetes/metabolismo , Nicotiana/genética , Nicotiana/metabolismo , Técnicas do Sistema de Duplo-Híbrido
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