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1.
Chem Senses ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32010937

RESUMO

Neuropeptide S (NPS) is an endogenous peptide recently recognized to be presented in the brainstem, and believed to play an important role in maintaining memory. The deletion of NPS or NPS receptor (NPSR) in mice shows a deficit in memory formation. Our recent studies have demonstrated that central administration of NPS facilitates olfactory function and ameliorates olfactory spatial memory impairment induced by muscarinic cholinergic receptor antagonist and N-methyl-D-aspartate receptor antagonist. However, it remains to be determined if endogenous NPS is an indispensable neuromodulator in the control of the olfactory spatial memory. In this study, we examined the effects of NPSR peptidergic antagonist [D-Val5]NPS (10 and 20 nmol, i.c.v.) and nonpeptidergic antagonist SHA 68 (10 and 50 mg/kg, i.p.) on the olfactory spatial memory using computer-assisted 4-hole-board olfactory spatial memory test in mice. Furthermore, immunofluorescence was employed to identify the distributions of c-Fos and NPSR immunoreactive (-ir) neurons in olfactory system and hippocampal formation known to closely relate to the olfactory spatial memory. [D-Val5]NPS dosing at 20 nmol and SHA 68 dosing at 50 mg/kg significantly decreased the number of visits to the two odorants interchanged spatially, switched odorants, in recall trial, and simultaneously reduced the percentage of Fos-ir in NPSR-ir neurons which were densely distributed in the anterior olfactory nucleus (AON), piriform cortex (Pir), subiculum (S), presubiculum (PrS) and parasubiculum (PaS). These findings suggest that endogenous NPS is a key neuromodulator in olfactory spatial memory.

2.
BMC Complement Med Ther ; 20(1): 15, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-32020863

RESUMO

BACKGROUND: Gastrointestinal cancer is one of the most common malignancies and imposes heavy burdens on both individual health and social economy. We sought to survey the effect of a self-care education program on quality of life and fatigue in gastrointestinal cancer patients who received chemotherapy. METHODS: Ninety-one eligible gastrointestinal cancer patients were enrolled in this study and 86 valid samples were analyzed. Data were acquired with a demographics questionnaire, endpoint multidimensional questionnaire and the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire QLQ-C30. The collected data were analyzed using SPSS software. RESULTS: The self-care education intervention significantly improved the quality of life with respect to emotional function (p = 0.018), role function (p = 0.041), cognitive function (p = 0.038) and alleviated side effects such as nausea/vomiting (p = 0.028) and fatigue (p = 0.029). Further analysis demonstrated that the self-care education benefited total fatigue, affective fatigue and cognitive fatigue in gastrointestinal cancer patients regardless of baseline depression. CONCLUSION: Our results suggested the beneficial effects of the self-care education in both quality of life and anti-fatigue in gastrointestinal cancer patients under chemotherapy. The self-care education could be considered as a complementary approach during combination chemotherapy in gastrointestinal cancer patients.

3.
Nat Cell Biol ; 22(2): 246-256, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32015438

RESUMO

The Hippo and mammalian target of rapamycin complex 1 (mTORC1) pathways are the two predominant growth-control pathways that dictate proper organ development. We therefore explored potential crosstalk between these two functionally relevant pathways to coordinate their growth-control functions. We found that the LATS1 and LATS2 kinases, the core components of the Hippo pathway, phosphorylate S606 of Raptor, an essential component of mTORC1, to attenuate mTORC1 activation by impairing the interaction of Raptor with Rheb. The phosphomimetic Raptor-S606D knock-in mutant led to a reduction in cell size and proliferation. Compared with Raptor+/+ mice, RaptorD/D knock-in mice exhibited smaller livers and hearts, and a significant inhibition of elevation in mTORC1 signalling induced by Nf2 or Lats1 and Lats2 loss. Thus, our study reveals a direct link between the Hippo and mTORC1 pathways to fine-tune organ growth.

4.
Sci Rep ; 10(1): 1839, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32020022

RESUMO

In recent years, large amounts of CO2 emissions have led to many environmental problems. Developing a reasonable approach to carbon dioxide emissions is one of the most important issues for the sustainable development of human civilization. Compared with CO2 geological storage, CO2 flooding has greater advantages and a higher utilization efficiency. CO2 flooding technology has been successfully applied to many types of reservoirs, such as conventional sandstone reservoirs, low-permeability reservoirs, and carbonates. In this paper, the feasibility of CO2 flooding in glutenite reservoirs is studied. First, the glutenite reservoir is divided into fine stages, and reasonable vertical development units are determined. On this basis, the distribution scale, genetic environment and formation mode of the glutenite reservoir are characterized in detail and their spatial distribution rules are depicted in three dimensions. Then, the influencing factors of CO2 flooding in the glutenite reservoir are analysed via reservoir numerical simulation technology. The effects of reservoir thickness, reservoir heterogeneity, macropores, dominant channels and fracturing on CO2 flooding efficiency are evaluated individually, and a set of reasonable parameters constituting an evaluation system for CO2 flooding in the glutenite reservoir is established. Finally, based on parameter optimization, the disadvantaged conditions of CO2 flooding in glutenite reservoirs are optimized, and their effects are gradually eliminated. In view of the characteristics of glutenite reservoirs, a unique three-dimensional well pattern arrangement is designed, different injection modes are optimized, and suitable injection agents are tested. These methods are conducive to improving the effect of reservoir parameters on CO2 flooding efficiency, allowing these reservoirs to be used for CO2 flooding. Based on these new methods, the displacement effect of the Yanjia-Yongan glutenite reservoir is predicted. Our results show that the reservoir has been developed efficiently and achieved a high recovery rate, the displacement front of the CO2 has become more uniform, and the sweep range has become wider. After extending the successful application of CO2 flooding in this reservoir to all of the glutenite reservoirs in the entirety of the Bohaiwan Basin, we predict that the oil recovery rate may reach 40%, with a cumulative oil recovery rate of approximately 3.04 × 108 t and a total CO2 consumption of 1.672 × 108 t. Thus, the proposed approach not only can improve the atmospheric environment but can also greatly improve the efficiency of oil displacement.

5.
Sci Rep ; 10(1): 2226, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32041989

RESUMO

Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure. A large proportion of genetic cause remains unexplained, especially in idiopathic DCM. We performed target next-generation sequencing of 102 genes which were known causes or candidate genes for cardiomyopathies and channelpathies in 118 prospectively recruited Han Chinese patients with idiopathic DCM. 41 of the 118 patients carried 40 pathogenic or likely pathogenic variants, providing a molecular diagnosis in 34.7% of patients. 32 of these variants were novel. TTN truncating variants were predominant, with a frequency of 31.0%, followed by variants of LMNA (14.3%), RBM20 (4.8%), and NEXN (4.8%). These 4 genes accounted for over half variants identified. No significant difference in clinical characteristics or rates of reaching the composite end point (cardiac transplantation and death from cardiac causes) between pathogenic or likely pathogenic variant carriers and noncarriers (hazard ratio 1.11, 95% CI: 0.41 to 3.00), or between patients with TTN truncating variants or without (hazard ratio 0.49, 95% CI: 0.36 to 6.10). In our prospective study, we first determined the overall genetic profiles and genotype-phenotype correlations in Han Chinese idiopathic DCM patients, which could provide insight for genetic diagnosis of DCM in this population.

6.
Medicine (Baltimore) ; 99(6): e18480, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32028385

RESUMO

This study aimed to synthetically evaluate the impact of intensive patients' education program (IEP) on anxiety, depression and patient global assessment (PGA) in diabetic foot ulcer (DFU) patients.One hundred eighty DFU patients with Wagner grade 1 and Wagner grade 2 were consecutively recruited in this randomized, controlled study and randomly assigned to IEP group (N = 90) or control group (N = 90) as 1:1 ratio. In the IEP group, patients received the IEP and usual care, and patients in the control group received usual care only. IEP included educating patients and their family members, supervising patients' harmful habits and diets, psychological care for the patients and establishing a patient-physician-nurse WeChat group. Hospital Anxiety and Depression Scale-anxiety/depression (HADS-A/D) and Zung Self-Rating Anxiety/depression Scale (SAS/SDS) were applied to assess anxiety/depression at M0-M3. PGA score was also assessed at M0-M3.For anxiety assessment, IEP group presented decreased HADS-A/SAS scores at M2/M3 and increased HADS-A/SAS score changes (M3-M0) compared to control group. For depression assessment, IEP group displayed reduced HADS-D/SDS scores at M2/M3 and raised SDS score change (M3-M0) compared to control group. Moreover, IEP group exhibited reduced PGA score at M1/M2/M3 and elevated PGA score change (M3-M0) compared to control group. Further subgroup analyses disclosed that IEP reduced HADS-A/SAS/HADS-D/PGA scores at M3 and elevated these score changes (M3-M0) in patients with Wagener grade 2 but not Wagener grade 1.IEP ameliorates anxiety, depression and PGA in DFU patients with Wagner grade 2 but not Wagner grade 1.


Assuntos
Transtornos de Ansiedade/terapia , Transtorno Depressivo/terapia , Pé Diabético/psicologia , Educação de Pacientes como Assunto , Pé Diabético/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Índice de Gravidade de Doença , Resultado do Tratamento
7.
Public Health Nutr ; : 1-7, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31948506

RESUMO

OBJECTIVE: To investigate whether implementation of a universal salt iodization (USI) programme has sufficient effects on pregnant women in Chongqing, the present study evaluated the iodine nutritional status of pregnant women living in Chongqing by spot urinary iodine concentration (UIC), to provide scientific suggestions to better meet the specific iodine needs of this vulnerable group. DESIGN: Cross-sectional design. SETTING: A random spot urine sample and household table salt sample were provided by each participant. PARTICIPANTS: A total of 2607 pregnant women from twenty-six of thirty-nine districts/counties in Chongqing participated. RESULTS: The overall median UIC of pregnant women was 171·80 µg/l (interquartile range (IQR) = 113·85-247·00 µg/l) and 40·97 % (n 1057) of participants were iodine insufficient. The median iodine in table salt samples was 25·40 mg/kg (IQR = 23·10-28·30 mg/kg); 93·26 % (n 2406) of samples examined were found to be adequately iodized. Iodine nutritional status was not significantly different according to table salt iodization category. Trimester was identified to be statistically associated with UIC (P < 0·01). Seven districts/counties had median UIC below 150 µg/l and one district had median UIC of 277·40 µg/l. CONCLUSIONS: The USI programme in Chongqing prevents iodine deficiency generally, but does not maintain iodine status within adequate and recommended ranges throughout pregnancy. Usage of non-iodized or unqualified iodized salt and the slight change of dietary habits of iodized salt in Chongqing may present a substantial challenge to fight iodine-deficiency disorders; more efforts are needed to ensure adequate iodine intake during pregnancy besides the USI programme.

8.
Cell Death Dis ; 11(1): 44, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31969558

RESUMO

Tissue nonspecific alkaline phosphatase (TNAP) is expressed widely in different tissues, modulating functions of metabolism and inflammation. However, the effect of TNAP on cardiac fibrosis remains controversial and needs to be further studied. The present study aims to investigate the role of TNAP on myocardial infarction (MI)-induced fibrosis and its mechanism. TNAP was upregulated in patients with MI, both in serum and injured hearts, and predicted in-hospital mortality. TNAP was also significantly upregulated after MI in rats, mostly in the border zone of the infarcted hearts combined with collagen synthesis. Administration of TNAP inhibitor, tetramisole, markedly improved cardiac function and fibrosis after MI. In the primary cultures of neonatal rat cardiac fibroblasts (CFs), TNAP inhibition significantly attenuated migration, differentiation, and expression of collagen-related genes. The TGF-ß1/Smads signaling suppression, and p-AMPK and p53 upregulation were involved in the process. When p53 inhibitor was administered, the antifibrotic effect of TNAP inhibition can be blocked. This study provides a direct evidence that inhibition of TNAP might be a novel regulator in cardiac fibrosis and exert an antifibrotic effect mainly through AMPK-TGF-ß1/Smads and p53 signals.

9.
Cell Biol Toxicol ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31993881

RESUMO

Taxol has been widely used as a first-line chemotherapeutic agent for the treatment of advanced nasopharyngeal carcinoma (NPC). However, acquired drug resistance has caused great difficulties in clinical treatment. Pyroptosis is a newly discovered programmed cell death pathway, and Caspase-1 and gasdermin D (GSDMD) play key roles in driving canonical pyroptosis. Increasing evidence suggests that pyroptosis is associated with the development of cancer; however, the function and mechanism of pyroptosis in NPC remain obscure. In this study, we observed that Taxol treatment caused pyroptotic cell death, along with activation of Caspase-1 and maturation of IL-1ß, as well as cleavage of GSDMD, which is the canonical pyroptosis executor. Furthermore, Taxol-induced pyroptotic cell death could be suppressed by Caspase-1 inhibitor (Z-YVAD-FMK) and GSDMD knockout. Moreover, NPC parental cells demonstrated higher levels of pyroptosis than Taxol-resistant cells, and pyroptosis mediated by Caspase-1/GSDMD suppression induced by a Caspase-1 inhibitor and GSDMD knockout could induce a Taxol-resistant phenotype in vitro and in vivo. By transfecting an siRNA targeting Beclin-1 into NPC Taxol-resistant cells, we discovered that autophagy could negatively regulate pyroptosis by inhibiting Caspase-1/GSDMD activation. Taken together, our results indicated that Caspase-1/GSDMD mediated Taxol-induced pyroptosis and a Taxol-resistant phenotype in NPC cell lines, which may be regulated by autophagy. Thus, we provide novel insight into the mechanisms of Taxol-induced cell death and a promising approach to improve the therapeutic outcomes of patients with advanced NPC.

10.
HLA ; 95(3): 212-213, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31900977

RESUMO

The HLA-B*46:41N allele differs from B*46:01:01:01 by a 13 nucleotides deletion at positions 275-287.

11.
Dis Model Mech ; 13(1)2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31953345

RESUMO

Receptor-interacting protein kinase 3 (RIPK3) was recently implicated in promoting atherosclerosis progression through a proposed role in macrophage necroptosis. However, RIPK3 has been connected to numerous other cellular pathways, which raises questions about its actual role in atherosclerosis. Furthermore, RIPK3 is expressed in a multitude of cell types, suggesting that it may be physiologically relevant to more than just macrophages in atherosclerosis. In this study, Ripk3 was deleted in macrophages, endothelial cells, vascular smooth muscle cells or globally on the Apoe-/- background using Cre-lox technology. To induce atherosclerosis progression, male and female mice were fed a Western diet for three months before tissue collection and analysis. Surprisingly, necroptosis markers were nearly undetectable in atherosclerotic aortas. Furthermore, en face lesion area was increased in macrophage- and endothelial-specific deletions of Ripk3 in the descending and abdominal regions of the aorta. Analysis of bone-marrow-derived macrophages and cultured endothelial cells revealed that Ripk3 deletion promotes expression of monocyte chemoattractant protein 1 (MCP-1) and E-selectin in these cell types, respectively. Western blot analysis showed upregulation of MCP-1 in aortas with Ripk3-deficient macrophages. Altogether, these data suggest that RIPK3 in macrophages and endothelial cells protects against atherosclerosis through a mechanism that likely does not involve necroptosis. This protection may be due to RIPK3-mediated suppression of pro-inflammatory MCP-1 expression in macrophages and E-selectin expression in endothelial cells. These findings suggest a novel and unexpected cell-type specific and athero-protective function for RIPK3.This article has an associated First Person interview with the first author of the paper.

12.
Basic Res Cardiol ; 115(2): 15, 2020 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932910

RESUMO

Myocardial ischemia-reperfusion (I/R) injury leads to intensive sympathetic nervous system (SNS) activation and inflammatory reactions. Whether renal sympathetic denervation (RDN) could be a new therapeutic strategy to modulate I/R inflammation and reduce infarct size after myocardial I/R injury needs to be explored. First, we investigated the correlation between plasma norepinephrine concentrations and circulating myeloid cell numbers in patients with acute myocardial infarction. And then, C57BL/6 mice underwent a "two-hit" operation, with 10% phenol applied to bilateral renal nerves to abrogate sympathoexcitation, and a 45-min ligation of the left coronary artery to induce myocardial I/R injury. The effects of RDN on the mobilization of immune cells in mice following myocardial I/R injury were explored. We observed a strong association between SNS overactivation and myeloid cell excessive accumulation in patients. In animal experiments, there was a significant reduction in infarct size per area at risk in the denervated-I/R group when compared to that of the innervated-I/R group (39.2% versus 49.8%; p < 0.005), and RDN also improved the left ventricular ejection fraction by 20% after 1 week. Furthermore, the denervated-I/R group showed a decrease in the number of neutrophils and macrophages in the blood and the myocardium as reflected by immunohistochemical staining and flow cytometry analysis (p < 0.05); the decrease was associated with a significant reduction in the circulating production of IL-1, IL-6 and TNF-α (p < 0.05). In summary, our study reveals a novel link between the SNS activity and inflammatory response undergoing myocardium I/R injury and identifies RDN as a potential therapeutic strategy against myocardium I/R injury via preserving the spleen immune cells mobilization.

13.
J Org Chem ; 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31927897

RESUMO

A novel and convenient visible light-catalyzed tandem radical cyclization of N-propargylindoles with acyl chlorides for accessing 2-acyl-9H-pyrrolo[1,2-a]indoles is established. This transformation involves sequential addition of the acyl radical to the carbon-carbon triple bond, intramolecular cyclization with the 2-position of indole, and isomerization of the carbon-carbon double bond. The experimental results show that this reaction contains a radical pathway and a radical chain process is not the major pathway for the formation of products.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31902775

RESUMO

Neural machine translation (NMT) heavily relies on context vectors generated by an attention network to predict target words. In practice, we observe that the context vectors for different target words are quite similar to one another and translations with such nondiscriminatory context vectors tend to be degenerative. We ascribe this similarity to the invariant source representations that lack dynamics across decoding steps. In this article, we propose a novel gated recurrent unit (GRU)-gated attention model (GAtt) for NMT. By updating the source representations with the previous decoder state via a GRU, GAtt enables translation-sensitive source representations that then contribute to discriminative context vectors. We further propose a variant of GAtt by swapping the input order of the source representations and the previous decoder state to the GRU. Experiments on the NIST Chinese-English, WMT14 English-German, and WMT17 English-German translation tasks show that the two GAtt models achieve significant improvements over the vanilla attention-based NMT. Further analyses on the attention weights and context vectors demonstrate the effectiveness of GAtt in enhancing the discriminating capacity of representations and handling the challenging issue of overtranslation.

15.
Fish Physiol Biochem ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31897859

RESUMO

The main purpose of this study was to evaluate the immunity, antioxidant indices, and disease resistance of quercetin in zebrafish (Danio rerio). A total of 630 fish were assigned to 21 tanks with 30 fish/tank, and they were exposed to 0, 0.01, 0.1, 1, 10, 100, and 1000 µg/L quercetin, respectively, for 56 days. Results indicated that the immune indices including acid phosphatase (ACP), myeloperoxidase (MPO), lysozyme activities, and Complement 3 (C3), C4, IgM contents were significantly higher in 1 µg/L quercetin group than these parameters in the control group (P < 0.05). TNF-α and IL-8 mRNA expressions significantly decreased as the levels of quercetin increased up to 1 µg/L and increased thereafter (P < 0.05). 1 and 10 µg/L quercetin groups showed significantly lower TNF-α and IL-8 mRNA levels than the quercetin-free group. Transforming growth factor-ß and IL-10 mRNA levels showed an obviously opposite trend with TNF-α expression. The SOD, GPX, CAT, T-AOC activities, and SOD and GPX gene expression in the liver were enhanced with increasing quercetin up to 1 µg/L, and decreased thereafter. MDA contents were affected by quercetin, in which 1 and 10 µg/L quercetin had a significantly lower level than that of the control group (P < 0.05). Defensin and Leap-II mRNA expression in the liver were the highest for fish exposed to 1 µg/L quercetin. The fish that exposed to 1 µg/L quercetin also showed a significantly higher survival rate than these of fish exposed to 0, 0.01, and 1000 µg/L quercetin (P < 0.05). In conclusion, the optimal level of quercetin promotes immunostimulant properties, antioxidant indices, and disease resistance of zebrafish.

16.
Fitoterapia ; 140: 104417, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31707125

RESUMO

Schefflera rubriflora, a plant native to Yunnan Province in China, is often used to treat ailments such as neuropathic pain, tracheitis, and cough. However, the active components imparting these pharmacological effects are largely unexplored. In this study, five novel lignans and three new derivatives of benzoid or pyran were isolated from the leaves and twigs of S. rubriflora. The structures of these compounds were determined by the comprehensive analyses of the 1D and 2D NMR spectra and ESI mass spectra and a comparison of the obtained data with those of the literature data. All the compounds were tested for the inhibition of IL-6 expression. Three of the isolated compounds could inhibit the expression by 52% to 72%.


Assuntos
Araliaceae/química , Interleucina-6/antagonistas & inibidores , Lignanas/farmacologia , Animais , China , Camundongos , Estrutura Molecular , Compostos Fitoquímicos/farmacologia , Folhas de Planta/química , Células RAW 264.7
17.
Eur J Med Chem ; 186: 111856, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31734021

RESUMO

Inhibiting the programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway is an attractive strategy for tumor immunotherapy. Here, a novel series of indoline-containing compounds were developed, among which, A13 was identified as the most promising PD-1/PD-L1 pathway inhibitor. At the biochemical level, A13 demonstrated strong inhibition of the PD-1/PD-L1 interaction, with an IC50 of 132.8 nM. Notably, it exhibited outstanding immunoregulatory activity, and significantly elevated interferon-γ secretion in a Hep3B/OS-8/hPD-L1 and CD3 T cell co-culture model, without significant toxic effect. Therefore, A13 could be employed as a suitable lead compound for further design of non-peptide inhibitors targeting the PD-1/PD-L1 interaction. In addition, the preliminary structure-activity relationships of these new indoline compounds were investigated in this study, providing valuable information for future drug development.

18.
Photochem Photobiol ; 96(1): 148-155, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31574562

RESUMO

DVDMS-2 is a novel candidate for photodynamic therapy of tumors. The purpose of the present study was to assess the distribution and elimination of DVDMS-2 in mice bearing hepatoma 22 tumors. DVDMS-2 (1, 2 and 4 mg kg-1 ) was injected intravenously into the mice, extracted from biological tissues and quantified using a fluorescence assay. The data obtained were processed with WinNonlin pharmacokinetic software. The fluorescence assay established for DVDMS-2 quantification was a rapid, reproducible, sensitive and specific method with good linearity. The pharmacokinetics of DVDMS-2 in tumor-bearing mice conformed to a two-compartment model. DVDMS-2 accumulated in tumor tissue to a greater extent than adjacent tissues (skin, muscle) and sustained a relatively high-level concentration 12 to 24 h following administration, which may be the optimal treatment time point. In conclusion, DVDMS-2 selectively accumulated in tumor tissue and was eliminated at a rapid rate in tumor-bearing mice, suggesting that DVDMS-2 may have few side effects, including skin phototoxicity. The present study established the pharmacokinetic characteristics of DVDMS-2, which may be beneficial in future clinical study.

19.
Mol Ther ; 28(2): 422-430, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31843447

RESUMO

Short hairpin RNAs that are delivered by recombinant adeno-associated virus (rAAV) have the potential to elicit long-term RNAi therapy for human disease. However, the discovery that short hairpin sequences can cause truncation of the rAAV genome calls into question the efficiency and gene-silencing specificity of this strategy in humans. Here, we report that embedding the guide strand of a small silencing RNA into an artificial microRNA (miRNA) scaffold derived from mouse miRNA-33 ensures rAAV genomic integrity and reduces off-targeting by 10-fold, while maintaining effective in vivo target gene repression in mice.

20.
Food Chem ; 303: 125367, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31442901

RESUMO

Fish muscle firmness is an important quality trait for consumer acceptance. Phosphorylation is known to change chemical and physical properties of proteins and is thus expected to affect muscle firmness, but only few such phosphoproteins have been identified. To explore phosphoproteins that affect fish muscle firmness, firm muscle (crisp grass carp) and soft muscle (ordinary grass carp) were analyzed by quantitative phosphoproteomics. We identified 27 up-regulated and 22 down-regulated phosphopeptides in crisp grass carp (ratio ≥1.5 or ≤0.667, and P-value < 0.05) and their potential upstream kinases. Protein-protein interaction analysis clustered these phosphoproteins into four groups, many of which have been suggested to impact muscle firmness and its postmortem changes: muscle fiber, connective tissue, carbohydrate metabolism and signal regulation. These results provide novel insights into the role of protein phosphorylation in fish muscle firmness and will contribute to the quality improvement of fish products.


Assuntos
Carpas/metabolismo , Proteínas de Peixes/metabolismo , Músculos/metabolismo , Fosfoproteínas/metabolismo , Proteômica , Animais , Fenômenos Biomecânicos , Alimentos Marinhos
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