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1.
Mol Ther Nucleic Acids ; 19: 339-349, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31877410

RESUMO

Circular RNAs (circRNAs) represent a class of noncoding RNAs with a wide expression pattern, and they constitute an important layer of the genome regulatory network. To date, the expression pattern and regulatory potency of circRNAs in the retina, a key part of the central nervous system, are not yet well understood. In this study, RNAs from five stages (E18.5, P1, P7, P14, and P30) of mouse retinal development were sequenced. A total of 9,029 circRNAs were identified. Most circRNAs were expressed in different stages with a specific signature, and their expression patterns were different from those of their host linear transcripts. Some circRNAs could act as sponges for several retinal microRNAs (miRNAs). Furthermore, circTulp4 could function as a competitive endogenous RNA (ceRNA) to regulate target genes. Remarkably, silencing circTulp4 in vivo led to mice having a thin outer nuclear layer (ONL) and defective retinal function. In addition, we found that circRNAs were dysregulated at a much earlier time point than that of disease onset in a retinal degeneration model (rd8 mice). In summary, we provide the first circRNA expression atlas during retinal development and highlight a key biological role for circRNAs in retinal development and degeneration.

2.
Acc Chem Res ; 52(10): 2784-2792, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31532621

RESUMO

Surface plasmons (SPs) originating from the collective oscillation of conduction electrons in nanostructured metals (Au, Ag, Cu, etc.) can redistribute not only the electromagnetic fields but also the excited carriers (electrons and holes) and heat energy in time and space. Therefore, SPs can engage in a variety of processes, such as molecular spectroscopy and chemical reaction. Recently, plenty of demonstrations have made plasmon-mediated chemical reactions (PMCRs) a very active research field and make it as a promising approach to facilitate light-driven chemical reactions under mild conditions. Concurrently, making use of the same SPs, surface-enhanced Raman spectroscopy (SERS) with a high surface sensitivity and energy resolution becomes a powerful and commonly used technique for the in situ study of PMCRs. Typically, various effects induced by SPs, including the enhanced electromagnetic field, local heating, excited electrons, and excited holes, can mediate chemical reactions. Herein, we use the para-aminothiophenol (PATP) transformation as an example to elaborate how SERS can be used to study the mechanism of PMCR system combined with theoretical calculations. First, we distinguish the chemical transformation of PATP to 4,4'-dimercaptoazobenzene (DMAB) from the chemical enhancement mechanism of SERS through a series of theoretical and in situ SERS studies. Then, we focus on disentangling the photothermal, hot electrons, and "hot holes" effects in the SPs-induced PATP-to-DMAB conversion. Through varying the key reaction parameters, such as the wavelength and intensity of the incident light, using various core-shell plasmonic nanostructures with different charge transfer properties, we extract the key factors that influence the efficiency and mechanism of this reaction. We confidently prove that the transformation of PATP can occur on account of the oxygen activation induced by the hot electrons or because of the action of hot holes in the absence of oxygen and confirm the critical effect of the interface between the plasmonic nanostructure and reactants. The products of these two process are different. Furthermore, we compare the correlation between PMCRs and SERS, discuss different scenario of PMCRs in situ studied by SERS, and provide some suggestions for the SERS investigation on the PMCRs. Finally, we comment on the mechanism studies on how to distinguish the multieffects of SPs and their influence on the PMCRs, as well as on how to power the chemical reaction and regulate the product selectivity in higher efficiencies.

3.
BMC Vet Res ; 15(1): 260, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31345215

RESUMO

BACKGROUND: The transmission of methicillin-resistant Staphylococcus aureus (MRSA) between humans and animals has been identified in a number of countries. In this study, MRSA in urban rodents and shrews in a community was investigated. Further, comparisons of MRSA isolates from rodents, shrews, and humans were conducted to evaluate the relationships of these isolates from different origins. RESULTS: Between 2015 and 2016, 397 oropharynx samples from 212 rodents and 185 shrews, and 8 MRSA isolates from hospital patients were collected. Twelve MRSA were isolated from the small mammals (3.0, 95%CI: 1.3-4.7%), including 11 isolates from rodents and one from a shrew. Three MRSA isolates from Rattus norvegicus were PVL-positive, and seven isolates were IEC-negative (one from Suncus murinus, five from Rattus norvegicus, and one from a patient). The spa type, MLST, and antimicrobial resistance patterns showed that the MRSA retrieved from rodents and shrews are likely related to human strains. CONCLUSION: MRSA derived from rodent shares similar antimicrobial resistance and molecular characteristics to those from humans, suggesting that urban rodents may play as maintenance host or vectors for MRSA which is important to human health.


Assuntos
Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Roedores/microbiologia , Musaranhos/microbiologia , Infecções Estafilocócicas/microbiologia , Animais , China/epidemiologia , Cidades , Farmacorresistência Bacteriana , Humanos , Staphylococcus aureus Resistente à Meticilina/classificação , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana , Epidemiologia Molecular , Tipagem de Sequências Multilocus , Infecções Estafilocócicas/epidemiologia , Fatores de Virulência/genética
4.
Vector Borne Zoonotic Dis ; 19(10): 781-783, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31216240

RESUMO

In recent years, hepatitis B virus (HBV) has been detected in some species of animals. In this study, we found HBV-like nucleotide sequences in murine rodents and Asian house shrews (Suncus murinus) collected in China. A total of 801 animals were trapped. We found that 0.48% (3/624) of the murine rodents and 1.69% (3/177) of Asian house shrews were positive for HBV-like DNA. Detection of HBV-like DNA in brown rats (Rattus norvegicus), rice-field rat (Rattus losea), and Asian house shrews indicated that these species of animals might be hosts for HBV. However, none of the HBV-like DNA-positive animals was additionally positive for anti-HBV antibodies or hepatitis B surface antigen. A 585 bp nucleic acid sequence, mapping to a hepadnavirus, was extracted from rice-field rat, and bores strong resemblance to human HBV genotype B sequences. Further research is required to investigate the hepadnaviruses within the murine rodent and Asian house shrew populations to uncover the origin and zoonotic potential of HBV.

5.
J Am Chem Soc ; 141(20): 8053-8057, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31070906

RESUMO

Surface plasmons (SPs) are able to promote chemical reactions through the participation of the energetic charge carriers produced following plasmons decay. Using p-aminothiophenol (PATP) as a probe molecule, we used surface-enhanced Raman spectroscopy to follow the progress of its transformation, in situ, to investigate systematically the role of hot electrons and holes. The energetic carrier mediated PATP oxidation was found to occur even in the absence of oxygen, and was greatly influenced by the interface region near the gold surface. The observed reaction, which occurred efficiently on Au@TiO2 nanostructures, did not happen on bare gold nanoparticles (NPs) or core-shell nanostructures when a silicon oxide layer blocked access to the gold. Moreover, the product of the PATP oxidation with oxygen on Au@TiO2 nanostructures differed from what was obtained without oxygen, suggesting that the mechanism through which "hot holes" mediated the oxidation reaction was different from that operating with oxygen activated by hot electrons.

6.
Hum Mutat ; 40(8): 1039-1045, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30998843

RESUMO

Retinitis pigmentosa (RP) is the most common manifestation of inherited retinal diseases with high degree of genetic, allelic, and phenotypic heterogeneity. CEP250 encodes the C-Nap1 protein and has been associated with various retinal phenotypes. Here, we report the identification of a mutation (c.562C>T, p.R188*) in the CEP250 in a consanguineous family with nonsyndromic RP. To gain insights into the molecular pathomechanism underlying CEP250 defects and the functional relevance of CEP250 variants in humans, we conducted a functional characterization of CEP250 variant using a novel Cep250 knockin mouse line. Remarkably, the disruption of Cep250 resulted in severe impairment of retinal function and significant retinal morphological alterations. The homozygous knockin mice showed significantly reduced retinal thickness and ERG responses. This study not only broadens the spectrum of phenotypes associated with CEP250 mutations, but also, for the first time, elucidates the function of CEP250 in photoreceptors using a newly established animal model.

7.
Invest Ophthalmol Vis Sci ; 60(4): 1265-1274, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30924851

RESUMO

Purpose: MicroRNA-182 (miR-182) is abundantly expressed in mammalian retinas; however, the association between miR-182 and retinal function remains unclear. In this study, we explored whether miR-182 contributes to functional decline in retinas using a miR-182 depleted mouse. Methods: Electroretinogram (ERG) amplitudes at different ages were measured in miR-182 knockout (KO) mice. The thickness and lamination of retinas were assessed using a color fundus camera and high-resolution optical coherence tomography. Expression levels of key photoreceptor-specific genes and the miR-183/96/182 cluster (miR-183C) were quantified using quantitative real-time PCR. RNA sequencing and light-induced damage were carried out to observe the changes in the retinal transcriptome and sensitivity to light damage in the miR-182 KO mice. Results: The ERG recording reveals that the ERG response amplitude decreased both at early and later ages when compared with control littermates. The expression of some key photoreceptor-specific genes was down-regulated with deletion of miR-182 in retina. RNA sequencing indicated that some biological processes of visual system were affected, and the numbers of potential target genes of miR-182 were presented in the mouse retina using bioinformatics analysis. The miR-182 KO mice were characterized by progressively losing the outer segment after being treated with light-damage exposure. The thickness and lamination of retina as well as compensatory expression of miR-183C showed no apparent changes in retina of miR-182 KO mice under normal laboratory lighting condition. Conclusions: Our findings provided new insights into the relationship between the miR-182 and retinal development and revealed that miR-182 may play a critical role in maintaining retinal function.


Assuntos
Sequência de Bases , MicroRNAs/genética , Retina/fisiopatologia , Degeneração Retiniana/genética , Deleção de Sequência , Animais , Modelos Animais de Doenças , Eletrorretinografia , Angiofluoresceinografia , Imuno-Histoquímica , Luz/efeitos adversos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Lesões Experimentais por Radiação/genética , Lesões Experimentais por Radiação/fisiopatologia , Reação em Cadeia da Polimerase em Tempo Real , Retina/efeitos da radiação , Degeneração Retiniana/fisiopatologia , Tomografia de Coerência Óptica
8.
RNA Biol ; 16(6): 821-829, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30874468

RESUMO

Circular RNAs (circRNAs) belong to an endogenous class of RNA molecules with both ends covalently linked in a circle. Although their expression pattern in the mammalian brain has been well studied, the characteristics and functions of circRNAs in retinas remain unknown. To reveal the whole expression profiles of circRNAs in the neural retina, we investigated retinal RNAs of human, monkey, mouse, pig, zebrafish and tree shrew and detected thousands of circRNAs showing conservation and variation in the retinas across different vertebrate species. We further investigated one of the abundant circRNAs, circPDE4B, identified in human retina. Silencing of circPDE4B significantly inhibited the proliferation of human A549 cells. Functional assays demonstrated that circPDE4B could sponge miR-181C, thereby altering the cell phenotype. We have explored the retinal circRNA repertoires across human and different vertebrates, which provide new insights into the important role of circRNAs in the vertebrate retinas, as well as in related human diseases.


Assuntos
/metabolismo , Retina/metabolismo , Células A549 , Animais , Linhagem Celular , Proliferação de Células/genética , Humanos , Camundongos , MicroRNAs/metabolismo , Vertebrados/genética , Vertebrados/metabolismo
9.
Hum Mutat ; 40(4): 392-403, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30609140

RESUMO

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder with four causative genes (SLC20A2, PDGFRB, PDGFB, and XPR1) that have been identified. Here, we aim to describe the mutational spectrum of four causative genes in a series of 226 unrelated Chinese PFBC patients. Mutations in four causative genes were detected in 16.8% (38/226) of PFBC patients. SLC20A2 mutations accounted for 14.2% (32/226) of all patients. Mutations in the other three genes were relatively rare, accounting for 0.9% (2/226) of all patients, respectively. Clinically, 44.8% of genetically confirmed patients (probands and relatives) were considered symptomatic. The most frequent symptoms were chronic headache, followed by movement disorders and vertigo. Moreover, the total calcification score was significantly higher in the symptomatic group compared to the asymptomatic group. Functionally, we observed impaired phosphate transport induced by seven novel missense mutations in SLC20A2 and two novel mutations in XPR1. The mutation p.D164Y in XPR1 might result in low protein expression through an enhanced proteasome pathway. In conclusion, our study further confirms that mutations in SLC20A2 are the major cause of PFBC and provides additional evidence for the crucial roles of phosphate transport impairment in the pathogenies of PFBC.

10.
Transbound Emerg Dis ; 66(1): 259-267, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30179306

RESUMO

Bocaparvovirus infections of humans and both wild and domestic animals have been widely reported around the world. In this study, we detected and genetically characterized porcine bocavirus (PBoV) carried by murine rodents (Rattus norvegicus, Rattus tanezumi, and Rattus losea) and house shrews (Suncus murinus) in China. Between May 2015 and May 2017, 496 murine rodents and 23 house shrews were captured in four Chinese provinces. Nested polymerase chain reaction was used to investigate the prevalence of PBoV in throat swab, faecal and serum samples. A total of 7.5% (39/519) throat swab samples, 60.5% (309/511) faecal samples, and 22.9% (52/227) serum samples were PBoV-positive. The prevalence among R. norvegicus and R. tanezumi was higher than that among R. losea and house shrews. PBoV-positive samples were found in all four provinces. Phylogenetic analysis based on partial viral capsid protein 1/2 (VP1/VP2) showed that sequences obtained in this study formed a novel group (PBoV G4). In addition, five near full-length PBoV genomes (4,715-4,798 nt) were acquired. These genomes encoded two non-structural proteins, NS1 (1,908 nt in four genomes and 1,923 nt in the remaining genome) and NP1 (600 nt), and the structural proteins, VP1/VP2 (1,851 nt). Phylogenetic analysis showed that PBoV G4 is distinct from rodent, human, and other bocaviruses. In conclusion, PBoV G4 prevalence was high among two common murine rodents in China, and the pathogenecity of PBoV G4 need to be further clarified.


Assuntos
Bocavirus/isolamento & purificação , Infecções por Parvoviridae/veterinária , Ratos , Doenças dos Roedores/epidemiologia , Musaranhos , Animais , China/epidemiologia , Fezes/virologia , Infecções por Parvoviridae/sangue , Infecções por Parvoviridae/epidemiologia , Infecções por Parvoviridae/virologia , Faringe/virologia , Filogenia , Reação em Cadeia da Polimerase/veterinária , Prevalência , Doenças dos Roedores/sangue , Doenças dos Roedores/virologia
11.
J Cancer ; 9(20): 3647-3650, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30405832

RESUMO

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers in China. Recently, a study identified that cullin 3 (CUL3) was significantly mutated and deleted in ESCC. We then hypothesis that germline variants in CUL3 may also associated with the susceptibility of ESCC. Variants in the gene 3'-untranslated region (3'-UTR) may associate with gene expression by altering miRNAs binding. Material and Methods: We systematically searched for variants in the 3'-UTR of CUL3 using the Ensembl database. Taqman SNP Genotyping Assay was performed in 638 ESCC cases and 546 controls to examine the association between the rs2396092 and the risk of ESCC. The eQTL analysis for CUL3 were conducted by using the GTEx database. Results: We identified that the rs2396092 was significantly associated with the susceptibility of ESCC. Compared with the TT genotype carriers, the CT genotype and CC genotype carriers were correlated with risk of ESCC with odds ratio being 1.33 (95% CI: 1.04-1.70, P=0.0222) and 1.63 (95% CI: 1.07-2.50, P=0.0241), respectively. Different genotypes of rs2396092 was also shown to be correlated with altered CUL3 expression. Conclusion: The results emphasize the importance of CUL3 in the development of ESCC and may contribute to the personalized prevention of this cancer in the future.

12.
Angew Chem Int Ed Engl ; 57(50): 16339-16342, 2018 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-30312507

RESUMO

Electrocatalytic CO2 reduction to CO emerges as a potential route of utilizing emitted CO2 . Metal-N-C hybrid structures have shown unique activities, however, the active centers and reaction mechanisms remain unclear because of the ambiguity in true atomic structures for the prepared catalysts. Herein, combining density-functional theory calculations and experimental studies, the reaction mechanisms for well-defined metal-N4 sites were explored using metal phthalocyanines as model catalysts. The theoretical calculations reveal that cobalt phthalocyanine exhibits the optimum activity for CO2 reduction to CO because of the moderate *CO binding energy at the Co site, which accommodates the *COOH formation and the *CO desorption. It is further confirmed by experimental studies, where cobalt phthalocyanine delivers the best performance, with a maximal CO Faradaic efficiency reaching 99 %, and maintains stable performance for over 60 hours.

13.
Neuron ; 98(6): 1116-1123.e5, 2018 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-29910000

RESUMO

Primary familial brain calcification (PFBC) is a genetically heterogeneous disorder characterized by bilateral calcifications in the basal ganglia and other brain regions. The genetic basis of this disorder remains unknown in a significant portion of familial cases. Here, we reported a recessive causal gene, MYORG, for PFBC. Compound heterozygous or homozygous mutations of MYORG co-segregated completely with PFBC in six families, with logarithm of odds (LOD) score of 4.91 at the zero recombination fraction. In mice, Myorg mRNA was expressed specifically in S100ß-positive astrocytes, and knockout of Myorg induced the formation of brain calcification at 9 months of age. Our findings provide strong evidence that loss-of-function mutations of MYORG cause brain calcification in humans and mice.


Assuntos
Astrócitos/metabolismo , Encefalopatias/genética , Calcinose/genética , Glicosídeo Hidrolases/genética , Mutação com Perda de Função , RNA Mensageiro/metabolismo , Adulto , Idoso , Alelos , Animais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Mutação , Linhagem
14.
J Biomed Opt ; 23(2): 1-10, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29473350

RESUMO

Optical coherence tomography (OCT) is an emergent imaging tool used for noninvasive diagnosis of skin diseases. The present meta-analysis was carried out to assess the accuracy of OCT for the diagnosis of skin cancer. We conducted a systematic literature search though EMBASE, Medline, PubMed, the Cochrane Library, and Web of Science database for relevant articles published up to June 6, 2017. The quality of the included studies was assessed using the QUADAS-2 tool and the Oxford Levels of Evidence Scale. Statistical analyses were conducted using the software Meta-Disc version 1.4 and STATA version 12.0. A total of 14 studies involving more than 813 patients with a total of 1958 lesions were included in our analyses. The pooled sensitivity and specificity of OCT for skin cancer diagnoses were 91.8% and 86.7%, respectively. Subgroup analysis showed that the pooled sensitivities of OCT for detecting basal cell carcinoma (BCC), squamous cell carcinoma (SCC), actinic keratosis, and malignant melanoma were 92.4%, 92.3%, 73.8%, and 81.0%, respectively. The pooled specificities were 86.9%, 99.5%, 91.5%, and 93.8%, respectively. OCT appears to be useful for the detection of BCC and SCC. It is a valuable diagnostic method when screening for early skin cancers.


Assuntos
Interpretação de Imagem Assistida por Computador , Melanoma/diagnóstico por imagem , Neoplasias Cutâneas/diagnóstico por imagem , Tomografia de Coerência Óptica , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
J Asian Nat Prod Res ; 20(8): 757-762, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28944682

RESUMO

Five caffeoyl phenylethanoid glycosides, including two new ones linderruelliosides A (1) and B (2), were isolated from the leaves and stems of Lindernia ruellioides. Their structures were elucidated on the basis of spectroscopic methods, including extensive NMR and MS spectra. In addition, all these compounds were tested for their anti-HBV activity. Compounds 1, 3, and 4 showed anti-HBV activities, with IC50 values of 54.87, 30.74, and 69.02 µM for HBsAg and 26.70, 5.17, and 7.08 µM for HBeAg, respectively.


Assuntos
Antivirais/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Scrophulariaceae/química , Antivirais/química , Linhagem Celular , China , Antígenos de Superfície da Hepatite B/análise , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Extratos Vegetais/química , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta
16.
Chem Biodivers ; 14(12)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29139211

RESUMO

Twenty-eight protostane triterpenoids, including a new degraded one (1), nine new ones (2 - 10), and two new natural ones (11 and 12), have been isolated from the dried rhizomes of Alisma orientale. Alisol R (1) was the first 20,21,22,23,24,25,26,27-octanorprotostane triterpenoid. The absolute configurations of 25-methoxyalisol F (2) and 16ß-hydroperoxyalisol B 23-acetate (3) were determined by X-ray diffraction analysis. In addition, alismaketone-B 23-acetate (28) showed potent vasorelaxant activity on endothelium-intact thoracic aorta rings precontracted with KCl.


Assuntos
Alisma/química , Terpenos/química , 11-beta-Hidroxiesteroide Desidrogenases/antagonistas & inibidores , 11-beta-Hidroxiesteroide Desidrogenases/metabolismo , Alisma/metabolismo , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Humanos , Espectroscopia de Ressonância Magnética , Camundongos , Conformação Molecular , Extratos Vegetais/química , Cloreto de Potássio/toxicidade , Ratos , Rizoma/química , Rizoma/metabolismo , Terpenos/metabolismo , Terpenos/farmacologia , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Vasodilatadores/química , Vasodilatadores/isolamento & purificação , Vasodilatadores/farmacologia , Difração de Raios X
17.
Proc Natl Acad Sci U S A ; 114(24): 6376-6381, 2017 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-28559309

RESUMO

MicroRNAs (miRNAs) are known to be essential for retinal maturation and functionality; however, the role of the most abundant miRNAs, the miR-183/96/182 cluster (miR-183 cluster), in photoreceptor cells remains unclear. Here we demonstrate that ablation of two components of the miR-183 cluster, miR-183 and miR-96, significantly affects photoreceptor maturation and maintenance in mice. Morphologically, early-onset dislocated cone nuclei, shortened outer segments and thinned outer nuclear layers are observed in the miR-183/96 double-knockout (DKO) mice. Abnormal photoreceptor responses, including abolished photopic electroretinography (ERG) responses and compromised scotopic ERG responses, reflect the functional changes in the degenerated retina. We further identify Slc6a6 as the cotarget of miR-183 and miR-96. The expression level of Slc6a6 is significantly higher in the DKO mice than in the wild-type mice. In contrast, Slc6a6 is down-regulated by adeno-associated virus-mediated overexpression of either miR-183 or miR-96 in wild-type mice. Remarkably, both silencing and overexpression of Slc6a6 in the retina are detrimental to the electrophysiological activity of the photoreceptors in response to dim light stimuli. We demonstrate that miR-183/96-mediated fine-tuning of Slc6a6 expression is indispensable for photoreceptor maturation and maintenance, thereby providing insight into the epigenetic regulation of photoreceptors in mice.


Assuntos
MicroRNAs/genética , MicroRNAs/metabolismo , Células Fotorreceptoras de Vertebrados/metabolismo , Animais , Visão de Cores/fisiologia , Eletrorretinografia , Epigênese Genética , Regulação da Expressão Gênica , Técnicas de Inativação de Genes , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Visão Noturna/fisiologia , Células Fotorreceptoras de Vertebrados/patologia , Células Fotorreceptoras Retinianas Cones/metabolismo , Células Fotorreceptoras Retinianas Cones/patologia , Degeneração Retiniana/genética , Degeneração Retiniana/metabolismo , Degeneração Retiniana/patologia
18.
J Exp Clin Cancer Res ; 36(1): 86, 2017 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-28646927

RESUMO

BACKGROUND: Homeobox B7 (HOXB7) has been identified associated with poor prognosis of hepatocellular carcinoma (HCC). However, the specific mechanism by which HOXB7 promotes the malignant progression of HCC remains to be determined. METHODS: Immunohistochemistry (IHC) was used to detect the expression level of HOXB7 in 77-paired HCC tissue samples, and the correlation between HOXB7 and HCC prognosis was assessed. The location of HOXB7 was confirmed by immunofluorescence. Cell Titer-Blue assay was used to assess the proliferation of hepatoma cells. The stem-like properties of hepatoma cells were analysed by sphere formation and clone formation assays. The effect of HOXB7 on expression of cancer stem cell markers was evaluated. Transwell and wound-healing assays were performed to estimate the invasion and migration abilities of hepatoma cells. A xenograft tumor model was established in nude mice to assess the role of HOXB7 in tumor growth. Bioluminescence imaging was used to survey the effect of HOXB7 on the metastatic ability of hepatoma cells in vivo. RESULTS: Higher expression of HOXB7 was detected in HCC tissues compared with noncancerous tissues and significantly associated with poor prognosis of HCC. In addition, HOXB7 knockdown suppressed the cell proliferation, clone formation, sphere formation, invasion and migration of hepatoma cells in vitro; conversely, these biological abilities of hepatoma cells were enhanced by HOXB7 overexpression. Moreover, the cancer stem cell markers EPCAM and NANOG were up-regulated by HOXB7. The role of HOXB7 in promoting tumor growth and metastasis was verified in vivo. Further investigation revealed that c-Myc and Slug expression was elevated by HOXB7 and the AKT pathway was activated. CONCLUSION: Overexpression of HOXB7 was significantly correlated with poor prognosis of HCC. HOXB7 up-regulated c-Myc and Slug expression via the AKT pathway to promote the acquisition of stem-like properties and facilitate epithelial-mesenchymal transition of hepatoma cells, accelerating the malignant progression of HCC.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Transição Epitelial-Mesenquimal/genética , Proteínas de Homeodomínio/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Células-Tronco Neoplásicas/metabolismo , Adulto , Idoso , Animais , Carcinoma Hepatocelular/mortalidade , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Progressão da Doença , Feminino , Expressão Gênica , Técnicas de Silenciamento de Genes , Genes myc , Xenoenxertos , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Camundongos , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica/genética , Estadiamento de Neoplasias , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Prognóstico , Fatores de Transcrição da Família Snail/genética , Carga Tumoral/genética
19.
Neural Dev ; 12(1): 4, 2017 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-28340616

RESUMO

BACKGROUND: The actin cytoskeleton-associated protein palladin plays an important role in cell motility, morphogenesis and adhesion. In mice, Palladin deficient embryos are lethal before embryonic day (E) 15.5, and exhibit severe cranial neural tube and body wall closure defects. However, the mechanism how palladin regulates the process of cranial neural tube closure (NTC) remains unknown. METHODS: In this paper, we use gene knockout mouse to elucidate the function of palladin in the regulation of NTC process. RESULTS: We initially focuse on the expression pattern of palladin and found that in embryonic brain, palladin is predominantly expressed in the neural folds at E9.5. We further check the major cellular events in the neural epithelium that may contribute to NTC during the early embryogenesis. Palladin deficiency leads to a disturbance of cytoskeleton in the neural tube and the cultured neural progenitors. Furthermore, increased cell proliferation, decreased cell differentiation and diminished apical cell apoptosis of neural epithelium are found in palladin deficient embryos. Cell cycle of neural progenitors in Palladin -/- embryos is much shorter than that in wt ones. Cell adhesion shows a reduction in Palladin -/- neural tubes. CONCLUSIONS: Palladin is expressed with proper spatio-temporal pattern in the neural folds. It plays a crucial role in regulating mouse cranial NTC by modulating cytoskeleton, proliferation, differentiation, apoptosis, and adhesion of neural epithelium. Our findings facilitate further study of the function of palladin and the underlying molecular mechanism involved in NTC.


Assuntos
Proteínas do Citoesqueleto/metabolismo , Defeitos do Tubo Neural/embriologia , Defeitos do Tubo Neural/metabolismo , Tubo Neural/embriologia , Tubo Neural/metabolismo , Fosfoproteínas/metabolismo , Animais , Apoptose , Adesão Celular , Ciclo Celular , Diferenciação Celular , Proliferação de Células , Proteínas do Citoesqueleto/genética , Citoesqueleto/metabolismo , Camundongos Knockout , Células-Tronco Neurais/metabolismo , Fosfoproteínas/genética
20.
J Pharm Biomed Anal ; 135: 67-74, 2017 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-28012307

RESUMO

A robust and highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of pericyazine in human plasma. The plasma sample was alkalized with sodium hydroxide solution and handled by liquid-liquid extraction with ethyl acetate after adding perphenazine as an internal standard (IS). The analytes were separated on an Ultimate™ AQ-C18 analytical column at 40°C, with a gradient elution consisting of A (aqueous phase: 5mM ammonium acetate buffer solution containing 0.1% formic acid) and B (organic phase: acetonitrile) at a flow rate of 0.350mL/min. The detection was conducted on an API 4000 tandem mass spectrometer coupled with electrospray ionization (ESI) source in positive ion mode. The multiple reaction monitoring (MRM) transitions, m/z 366.5>142.4 for pericyazine, m/z 382.5>142.4 for its 7-hydroxy and sulphoxide metabolites and m/z 404.3>171.3 for IS were chosen to achieve high selectivity in the simultaneous analyses. The method exhibited great improvement in sensitivity (LLOQ of 0.021ng/mL) and good linearity over the concentration range of 0.021-9.90ng/mL. The intra- and inter-day precision, accuracy, and stability results were within the acceptable limits and no matrix effect was observed. This method was successfully applied in a bioequivalence study to evaluate the pharmacokinetics in 20 healthy male Chinese volunteers. Additional exploratory analyses of 7-hydroxy and sulphoxide metabolites of pericyazine in the same samples suggest that the unchanged drug is predominant in the plasma and suitable for the bioequivalence comparison after a single oral administration of 10mg pericyazine.


Assuntos
Grupo com Ancestrais do Continente Asiático , Fenotiazinas/sangue , Sulfóxidos/sangue , Espectrometria de Massas em Tandem/normas , Adulto , Cromatografia Líquida/métodos , Cromatografia Líquida/normas , Estudos Cross-Over , Voluntários Saudáveis , Humanos , Masculino , Fenotiazinas/análise , Sulfóxidos/análise , Espectrometria de Massas em Tandem/métodos , Equivalência Terapêutica , Adulto Jovem
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