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1.
J Agric Food Chem ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32011875

RESUMO

Serotonin is an important endogenous regulatory neurotransmitter and has also been found in fruits, vegetables, and nuts. Methylglyoxal (MGO) is a reactive dicarbonyl metabolite and also a food toxin that modifies protein and DNA to cause the development of many chronic diseases. The objective of this study is to understand the reaction mechanisms between serotonin and MGO and determine whether serotonin could trap MGO in vivo. Five products were detected in phosphate buffer (pH 7.4) at 37 °C. Four products (compounds 2 and 4-6) were purified from the reaction mixture, and their structures were characterized by the analysis of their high-resolution mass and one- and two-dimensional nuclear magnetic resonance spectra. One product (compound 3), as a result of its instability, could not be properly purified and was tentatively characterized on the basis of its high-resolution mass spectrum and corresponding mass fragments. On the basis of the structures of these five products, two reaction pathways were proposed. Compounds 2, 3, 5, and 6 were produced through the Pictet-Spengler condensation pathway between the primary amine of serotonin and the ketone of MGO, and compound 3 was identified as the intermediate product to form products 2, 5, and 6, whereas compound 4 was formed through nucleophilic substitution by the benzene ring of serotonin, which is a new reaction pathway between biogenic amines and reactive carbonyl species. More importantly, the detection of adducts 2 and 4-6 in mice supports our hypothesis that the reaction between serotonin and MGO also happens in vivo through the same pathways as those in model reactions, suggesting that dietary or endogenous serotonin has the capacity to trap MGO in vivo.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32048201

RESUMO

Messenger RNA (mRNA) vaccines have attracted great interest in recent years due to their high potency, safety profile, and potential of rapid development. Although a number of mRNA vaccines have entered clinical trials, there remain several challenges. Inefficient in vivo delivery of mRNA is the foremost one. Here we synthesized a conjugate composed of ß-cyclodextrin (ß-CD) and branched polyethyleneimine (molecular weight 2 kDa, bPEI2k) to deliver an mRNA vaccine. The CD-PEI (CP) conjugate helped the encapsulated mRNA molecules pass through the plasma membranes and escape from the endosomes, which consequently ensured high transfection efficiency. On this basis, we optimized several structural elements of mRNA molecules via synthesizing an advanced cap structure and incorporating untranslated regions (UTRs) and an extended poly(A) tail into the sequence. These modifications led to a higher expression level of encoded proteins, which was expected to induce potent immune responses with a relatively low dosage. We also investigated the relevance of the administration route to the immune responses induced by CP-assisted mRNA vaccines with in vivo evidence, providing a basis for the selection of optimum administration route in specific cases. This CP-based mRNA vaccine platform, with an optimized mRNA structure and administrated in a most appropriate route, holds a promise to be applied to specific antigens in the future. Graphical abstract.

3.
Mol Ther ; 28(1): 313-327, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31604679

RESUMO

MicroRNAs (miRNAs) play an essential role in the self-renewal of breast cancer stem cells (BCCs). Our study aimed to clarify the role of proto-oncogene c-Jun-regulated miR-5188 in breast cancer progression and its association with Timeless-mediated cancer stemness. In the present study, we showed that miR-5188 exerted an oncogenic effect by inducing breast cancer stemness, proliferation, metastasis, and chemoresistance in vitro and in vivo. The mechanistic analysis demonstrated that miR-5188 directly targeted FOXO1, which interacted with ß-catenin in the cytoplasm, facilitated ß-catenin degradation, and impaired the nuclear accumulation of ß-catenin, thus stimulating the activation of known Wnt targets, epithelial-mesenchymal transition (EMT) markers, and key regulators of cancer stemness. Moreover, miR-5188 potentiated Wnt/ß-catenin/c-Jun signaling to promote breast cancer progression. Interestingly, c-Jun enhanced miR-5188 transcription to form a positive regulatory loop, and Timeless interacted with Sp1/c-Jun to induce miR-5188 expression by promoting c-Jun-mediated transcription, which further activated miR-5188-FOXO1/ß-catenin-c-Jun loop and facilitated breast cancer progression. Importantly, miR-5188 was upregulated in breast cancer and was positively correlated with poor patient prognosis. This study identifies miR-5188 as a novel oncomiR and provides a new theoretical basis for the clinical use of miR-5188 antagonists in the treatment of breast cancer.

4.
Sci Total Environ ; 711: 134996, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31818589

RESUMO

Three types of greenhouse gases (GHGs), namely carbon dioxide, methane and nitrous oxide emitted from reservoirs have an important but often ignored impact on the climate change. Based on the literature, this paper presents a comprehensive assessment of the long-term impact of GHGs generated by hydropower reservoirs, the systems for monitoring and assessing reservoir GHGs, the mechanism for their generation and key factors involved. Using limnology theory as a basis, the biogeochemical cycle of carbon in the environment is understood to be the main mechanism for generating reservoir based GHG emissions. A summary of relevant research in South American tropical rain forests and the Canada's temperate zone, also shows the extent of current systematic analysis of GHG emission research. Proposals are made for more comprehensive data collection from a wider variety of sources and the key problems identified that need to be solved to provide a theoretical basis for future development policies and practice.

5.
Int J Food Microbiol ; 317: 108463, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31809966

RESUMO

Paocai is a widely consumed Chinese traditional fermented vegetable product. To understand the effect of temperature on paocai fermentation flora, the bacterial community structure of paocai fermented at 10 °C, 15 °C, 25 °C and 35 °C was analyzed by culture-dependent and culture-independent methods. The results showed that increasing the fermentation temperature in a certain range is beneficial for rapid paocai acid production and shortening of the maturity period. Illumina Miseq sequencing was performed on 56 samples at different fermentation process temperatures using a culture-independent method. A total of 1,964,231 high-quality reads of 16S rRNA V3-V4 regions were obtained, and they were divided into 405 operational taxonomic units (OTUs) and identified as 213 bacterial genera. The bacterial diversity decreased with the progression of fermentation, and some spoiled samples had an increased diversity. The culture-independent method found that at 10 °C, Lactococcus appeared at the start of fermentation, Leuconostoc and Weissella appeared in the middle of fermentation, and Lactobacillus and Leuconostoc dominated fermentation in the late stage. At 15 °C, Lactococcus started fermentation, Leuconostoc appeared in the middle stage, and Lactobacillus was dominant in the late stage. At 25 °C, Lactococcus started fermentation, Weissella and Lactobacillus appeared in the middle stage, and Lactobacillus dominated fermentation in the late stage. Finally, at 35 °C, Lactococcus, Weissella, and Lactobacillus started fermentation, Weissella and Lactobacillus appeared in the middle stage, and Lactobacillus dominated fermentation in the late stage. A total of 647 strains of bacteria were isolated by culture-dependent methods and were divided into 12 genera and 19 species by randomly amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) and 16S ribosomal RNA gene (rDNA) sequencing technology. More types of bacteria were isolated in the early stage of fermentation. At 10 °C, Lactococcus lactis began fermentation, and Lactobacillus brevis and Leuconostoc mesenteroides dominated acid production in the middle and late stages of paocai fermentation. At 15 °C, L. lactis initiates fermentation, while Lactobacillus plantarum dominates the acid fermentation of paocai. At 25 °C and 35 °C, there were a large number of Enterobacteriaceae bacteria in the start-up fermentation stage, and L. plantarum was dominant after 1-2 days of fermentation. Redundancy analysis (RDA) found that the lower the temperature, the more bacterial species that are produced, and the higher the temperature and the longer the time, the more obvious are the effects of L. plantarum on paocai. The results of dominant bacteria studied by culture-dependent and culture-independent methods are similar. The results indicate that most of the dominant microorganisms in the paocai fermentation system are culturable. This discovery can provide data and physical support for modernization and regulation of different types of paocai production.

6.
J Agric Food Chem ; 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31841331

RESUMO

Avenanthramides (AVAs) are unique phytochemicals in oat that contain two distinct groups of compounds. The first group is constituted by N-cinnamoylanthranilic acids with a single double bond (referred to as C type), and the other group is constituted by N-avenalumoylanthranilic acids with two double bonds (referred to as A type). C-type AVAs have been reported with their chemical profiles and levels in commercial oat products as well as their bioactivities. However, the accurate levels of A-type AVAs in commercial sprouted oat products and their bioactivity are still unknown. In this study, we purified seven A-type AVAs from sprouted oat bran and characterized their structures with corresponding mass spectrometry and nuclear magnetic resonance data. Among them, five compounds were isolated from oat bran for the first time. The purified A-type AVAs were used as authentic standards to establish the chemical profile of A-type AVAs in oat and to quantify the levels of all individual A-type AVAs in six commercial sprouted oat products using ultra-high-performance liquid chromatography with tandem mass spectrometry. The total A-type AVA contents in the various oat products ranged from 7.85 to 133.3 µg/g. Furthermore, the inhibition of lipopolysaccharide-induced nitric oxide production and inducible nitric oxide synthase expression by A- and C-type AVAs in macrophages were compared. The most abundant A-type AVAs (2pd, 2cd, and 2fd) have similar anti-inflammatory activity to the major C-type AVAs (2p, 2c, and 2f). To the best of our knowledge, this is the first report on the bioactivity of A-type AVAs.

7.
Technol Cancer Res Treat ; 18: 1533033819875166, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31769345

RESUMO

OBJECTIVE: To construct plasmids with Hre2.Grp78 chimeric promoter regulating fusion gene TK/VP3 and elaborate the effects of overexpressed TK/VP3 on nasopharyngeal carcinoma cells. METHODS: Four plasmids were constructed, including pcDNA3.1-CMV-TK/VP3, pcDNA3.1-Hre2.TK/VP3, pcDNA3.1-Grp78.TK/VP3, and pcDNA3.1-Hre2.Grp78.TK/VP3. The human nasopharyngeal carcinoma cell line HNE1 cells were transfected with the 4 plasmids, respectively. Cell viabilities were evaluated using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and apoptosis was conducted using flow cytometry analysis. The expression of TK, VP3, Grp78, and hypoxia-inducible factor 1α and apoptosis-related proteins was determined by real-time quantitative polymerase chain reaction and Western blotting. RESULTS: The recombinant plasmids that could steadily overexpress TK and VP3 were successfully constructed. Expression of TK and VP3 in cells transfected with pcDNA3.1-Hre2.TK/VP3 and pcDNA3.1-Grp78.TK/VP3 was significantly higher than pcDNA3.1-CMV-TK/VP3, and expression in cells transfected with pcDNA3.1-Hre2.Grp78.TK/VP3 was the highest. Under glucose deprivation or hypoxia condition, Grp78 or hypoxia-inducible factor 1α was overexpressed so that expression of TK and VP3 was significantly upregulated, which could further inhibit cell proliferation and enhance cell apoptosis. CONCLUSION: We successfully constructed 4 plasmids with Hre2.Grp78 chimeric promoter regulating fusion gene TK/VP3, which could significantly inhibit the proliferation as well as enhance the apoptosis of nasopharyngeal carcinoma cells under glucose deprivation or hypoxia condition.

8.
Math Biosci Eng ; 16(6): 6805-6821, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31698589

RESUMO

p62/SQSTM1 is the scaffold protein implicated in selective autophagy, which is induced by cellular stress. Research has shown that p62 is highly expressed in cancer. Moreover, p62 can easily promote tumor metastasis. However, studies have not reached a consensus on the relationship of p62 expression with the diagnosis and prognosis of lung cancer. We conducted a systematic review and meta-analysis of studies on p62 expression in the prognosis and clinical-pathological parameters of lung cancer patients. Literature search was performed with PubMed, Web of Science, EMBASE, Cochrane Library, and SpringerLink databases. Fixed-effects and random-effects models were used to study the relationship of p62 expression with patients' overall survival (OS) and clinical-pathological parameters. I2 was used to test for heterogeneity. Egger's test was used to assess publication bias. The meta-analysis collected and considered 13 articles, which included 1393 lung cancer patients. The studies show that the high expression of p62 is associated with poor OS in lung cancer patients. The clinical-pathological parameters of patients show that p62 is more highly expressed in high TNM stage (II + III + IV VS. I), Lymph node metastasis (N1 VS. N0), and distant metastases (D1 VS. D0). However, there is no correlation between the p62 expression and the Beclin 1 and LC3B in lung cancer patients. In conclusion, the over-expression of p62 is associated with poor OS in lung cancer patients and can be used as a biomarker for lung cancer diagnosis and prognosis.

9.
Am J Transl Res ; 11(9): 5390-5403, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632518

RESUMO

The repair of long-segment tracheal defects remains a significant clinical challenge, to which, optimal biologically functioning tracheal alternatives may serve as a solution. Tissue-engineered trachea, regenerated from a decellularized trachea matrix using the laser micropore technique (LDTM), demonstrates the possibility of developing optimal tracheal substitutes, which retain the original tubular shape and adequate cartilage regeneration ability of trachea. However, the strict requirement with respect to the implantation cell density restricts the clinical translation of the LDTM, which has a low cell adherence rate. To overcome this problem, we propose a novel strategy involving collagen to modify the LDTM surface in order to enhance cell retention efficiency and promote homogeneous tracheal cartilage regeneration. The current results show that the modified LDTM significantly improves cell-seeding efficiency; moreover, it achieved stable cell retention and homogenous cell distribution. Additionally, at a relatively low implantation cell density (5.0 × 107 cells/mL, which is one-fourth of the cell-seeding density used in our previous study), homogeneous tubular cartilage was regenerated successfully both in vitro and in vivo. The cartilage had an exact tracheal shape, sufficient mechanical strength, typical lacuna structure, and cartilage-specific extracellular matrix deposition. Most importantly, the modified LDTM promoted chondrogenesis of the bone marrow-derived stem cells and the formation of homogeneous neocartilage in vivo. The current study has established a versatile and efficient cell-seeding strategy for the regeneration of multiple tissues. It also describes a technique for developing an optimal tracheal alternative for the repair and functional reconstruction of long-segment tracheal defects.

10.
Therap Adv Gastroenterol ; 12: 1756284819878046, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31598135

RESUMO

Background: Nonalcoholic fatty liver disease (NAFLD) has become prevalent in recent decades, especially in developed countries, and approaches for the prevention and treatment of NAFLD are not clear. The aim of this research was to analyze and summarize randomized controlled trials that investigated the effects of probiotics on NAFLD. Methods: Seven databases (PubMed, Embase, the Web of Science, the Cochrane Library, China National Knowledge Infrastructure, Wan Fang Data, and VIP Database) were searched. Then, eligible studies were identified. Finally, proper data extraction, synthesis and analysis were performed by trained researchers. Results: Anthropometric parameters: with use of probiotics weight was reduced by 2.31 kg, and body mass index (BMI) was reduced by 1.08 kg/m2. Liver function: probiotic treatment reduced the alanine aminotransferase level by 7.22 U/l, the aspartate aminotransferase level by 7.22 U/l, the alkaline phosphatase level by 25.87 U/l, and the glutamyl transpeptidase level by -5.76 U/l. Lipid profiles: total cholesterol, low-density lipoprotein cholesterol, and triglycerides were significantly decreased after probiotic treatment. Their overall effects (shown as standard mean difference) were -0.73, -0.54, and -0.36, respectively. Plasma glucose: probiotics reduced the plasma glucose level by 4.45 mg/dl and the insulin level by 0.63. Cytokines: probiotic treatment decreased tumor necrosis factor alpha by 0.62 and leptin by 1.14. Degree of liver fat infiltration (DFI): the related risk of probiotics for restoring DFI was 2.47 (95% confidence interval, 1.61-3.81, p < 0.001). Conclusion: Probiotic treatment or supplementation is a promising therapeutic method for NAFLD.

11.
Aging (Albany NY) ; 11(18): 7817-7829, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31546234

RESUMO

PRL-3, an oncogenic dual-specificity phosphatase, is overexpressed in 50% of acute myeloid leukemia patients. Stathmin has been identified as a downstream target of PRL-3 in colorectal cancer. However, the correlation between PRL-3 and stathmin in myeloid leukemia is unclear. In this study, we revealed the positive correlation between PRL-3 and stathmin in myeloid leukemia. Knockdown of the PRL-3 gene by shRNA reduced the expression of downstream stathmin, suppressed cell proliferation, induced G2/M arrest and cell apoptosis, and inhibited migration and invasion in myeloid leukemia cells. Moreover, our study was the first to provide evidence that silencing PRL-3 increased the phosphorylation level in Ser16, Ser25, Ser38, and Ser63 of stathmin, and in turn inhibited the STAT3 and STAT5 signaling in myeloid leukemia cells. This evidence points to a promoted role for PRL-3 in the progression of myeloid leukemia, and PRL-3 could be a possible new treatment target.

12.
Virol Sin ; 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31552609

RESUMO

Beak and feather disease virus (BFDV) is an infectious agent responsible for feather degeneration and beak deformation in birds. In March 2017, an epidemic of psittacine beak and feather disease (PBFD) struck a farm in Fuzhou in the Fujian Province of southeast China, resulting in the death of 51 parrots. In this study, the disease was diagnosed and the pathogen was identified by PCR and whole genome sequencing. A distinct BFDV strain was identified and named as the FZ strain. This BFDV strain caused severe disease symptoms and pathological changes characteristic of typical PBFD in parrots, for example, loss of feathers and deformities of the beak and claws, and severe pathological changes in multiple organs of the infected birds. Phylogenetic analysis showed that the FZ strain was more closely related to the strain circulating in New Caledonia than the strains previously reported in China. Nucleotide homology between the FZ strain and other 43 strains of BFDV ranged from 80.0% to 92.0%. Blind passage experiment showed that this strain had limited replication capability in SPF Chicken Embryos and DF-1 Cells. Furthermore, the capsid (Cap) gene of this FZ strain was cloned into the pGEX-4T-1 expression vector to prepare the polyclonal anti-Cap antibody. Western blotting analysis using the anti-Cap antibody further confirmed that the diseased parrots were infected with BFDV. In this study, a PBFD and its pathogen was identified for the first time in Fujian Province of China, suggesting that future surveillance of BFDV should be performed.

13.
Yi Chuan ; 41(8): 746-753, 2019 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-31447425

RESUMO

Personal genomic information benefits from accumulated big data and its application is no longer limited to scientific research. Presently, it is undergoing the transformation to daily medical practice. Systematic arrangement, archiving and rational utilization of disease-related genomic information is an important foundation of future precision medicine. Hemoglobinopathy is prevalent in southern China, but its molecular pathological basis has racial specificity. To facilitate clinical diagnosis and genetic screening of hemoglobinopathy in southern China, we established the LOVD gene data management system for the variation and phenotype spectrum of hemoglobinopathy. Then we designed an integrated and efficient on-line auxiliary accurate diagnosis and risk assessment system in order to assist clinicians to make comprehensive diagnosis and genetic counseling in a short time based on cloud standardized annotated library of specific hemoglobinopathy variants and diagnostic repository. The methodology and experience of improving the clinical decision-making efficiency of diseases with big data and artificial intelligence technology can be used as an example in the clinical and preventive application of other diseases.


Assuntos
Bases de Dados Genéticas , Sistemas de Apoio a Decisões Clínicas , Hemoglobinopatias/genética , Mutação , China , Aconselhamento Genético , Testes Genéticos , Humanos
14.
Artigo em Inglês | MEDLINE | ID: mdl-31327109

RESUMO

The utilization of reclaimed water is one of the effective measures to save water resources. The study of reclaimed water irrigation and the analysis of how heavy metals migrate in the soil, especially their movement laws, have important theoretical and practical significance. It helps to predict the risk of heavy metals in foods, which protects our health and safety. In this paper, we studied the accumulation and distribution of heavy metal Cd in soils with reclaimed water drip irrigation in greenhouses during growing season, comparing the effects with groundwater drip irrigation. The results show that the Cd concentration in the surface soil is the highest on the second day after drip irrigation. It will be the highest on the fourth day in the depth of 100 cm, and then, it will decrease slightly. During the period of the sixth day to the eighth day, the Cd concentrations are similar in each depth, and it is the highest in the depth of 0-40 cm and 80-120 cm, but the Cd concentration decreases with the lower depth below 120 cm. By utilizing proper ways of reclaimed water drip irrigation, the Cd concentration in the deep soil will not violate the standard limits of GB15618-1995, which will not cause Cd pollution.

15.
CNS Neurosci Ther ; 25(9): 1030-1041, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31218845

RESUMO

INTRODUCTION: L-glutamine is an antioxidant that plays a role in a variety of biochemical processes. Given that oxidative stress is a key component of stroke pathology, the potential of L-glutamine in the treatment of ischemic stroke is worth exploring. AIMS: In this study, we investigated the effect and mechanisms of action of L-glutamine after cerebral ischemic injury. RESULTS: L-glutamine reduced brain infarct volume and promoted neurobehavioral recovery in mice. L-glutamine administration increased the expression of heat-shock protein 70 (HSP70) in astrocytes and endothelial cells. Such effects were abolished by the coadministration of Apoptozole, an inhibitor of the ATPase activity of HSP70. L-glutamine also reduced oxidative stress and neuronal apoptosis, and increased the level of superoxide dismutase, glutathione, and brain-derived neurotrophic factor. Cotreatment with Apoptozole abolished these effects. Cell culture study further revealed that the conditioned medium from astrocytes cultured with L-glutamine reduced the apoptosis of neurons after oxygen-glucose deprivation. CONCLUSION: L-glutamine attenuated ischemic brain injury and promoted functional recovery via HSP70, suggesting its potential in ischemic stroke therapy.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31115718

RESUMO

Water is a crucial factor for human living and maintaining ecological system health. Water resource conflict has become an important factor which restricts regional economic development and affects the harmony and stability of society. This paper, on the one hand, builds a trilateral evolution game model of water intaking in the upper, middle, and lower reaches in terms of water-quality conflict, and makes an analysis of the evolutionary stable strategy of the model on the foundation of a cross-border water resource conflict warning system and based on the view of evolution game. The paper verifies related conclusions by using numerical simulation calculation examples and makes sensitivity analysis of the change of the parameters of the model. The result of the research indicates that (1) there are three groups of system local gradual stable points [Formula: see text] and [Formula: see text] in the trilateral game of water quality-based cross-border conflicts. This means that there are three groups of evolutionary stable strategies: (non-cooperation, non-cooperation, cooperation), (cooperation, non-cooperation, cooperation), and (non-cooperation, cooperation, cooperation). The conclusion obtained via verification by using numerical simulation is that upper and middle reaches are the sections which most likely lead to conflicts, so the strategy selected therefor is (non-cooperation, non-cooperation, cooperation); (2) in water quality-based cross-border conflict, the factor [Formula: see text] of compensation cost increased because excessive transfer of pollutants has a significant effect on water-intaking group strategy evolution path. It is of great theoretical and practical significance to the scientific operation of cross-border water quality and water amount conflicts and the realization of the goal of water resources management.

18.
J Hered ; 110(6): 641-650, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31102441

RESUMO

The South China tiger (Panthera tigris amoyensis) is endemic to China and also the most critically endangered subspecies of living tigers. It is considered extinct in the wild and only about 150 individuals survive in captivity to date, whose genetic heritage, however, is ambiguous and controversial. Here, we conducted an explicit genetic assessment of 92 studbook-registered South China tigers from 14 captive facilities using a subspecies-diagnostic system in the context of comparison with other voucher specimens to evaluate the genetic ancestry and level of distinctiveness of the last surviving P. t. amoyensis. Three mtDNA haplotypes were identified from South China tigers sampled in this study, including a unique P. t. amoyensis AMO1 haplotype not found in other subspecies, a COR1 haplotype that is widespread in Indochinese tigers (P. t. corbetti), and an ALT haplotype that is characteristic of Amur tigers (P. t. altaica). Bayesian STRUCTURE analysis and parentage verification confirmed the verified subspecies ancestry (VSA) as the South China tiger in 74 individuals. Genetic introgression from other tigers was detected in 18 tigers, and subsequent exclusion of these and their offspring from the breeding program is recommended. Both STRUCTURE clustering and microsatellite-based phylogenetic analyses demonstrated a close genetic association of the VSA South China tigers to Indochinese tigers, an issue that could only be elucidated by analysis of historical South China tiger specimens with wild origin. Our results also indicated a moderate level of genetic diversity in the captive South China tiger population, suggesting a potential for genetic restoration.

19.
J Biol Chem ; 294(21): 8577-8591, 2019 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-30971429

RESUMO

Enhancer of zeste homolog 2 (EZH2), an epigenetic regulator that plays a key role in cell differentiation and oncogenesis, was reported to promote adipogenic differentiation in vitro by catalyzing trimethylation of histone 3 lysine 27. However, inhibition of EZH2 induced lipid accumulation in certain cancer and hepatocyte cell lines. To address this discrepancy, we investigated the role of EZH2 in adipogenic differentiation and lipid metabolism using primary human and mouse preadipocytes and adipose-specific EZH2 knockout (KO) mice. We found that the EZH2-selective inhibitor GSK126 induced lipid accumulation in human adipocytes, without altering adipocyte differentiation marker gene expression. Moreover, adipocyte-specific EZH2 KO mice, generated by crossing EZH2 floxed mice with adiponectin-Cre mice, displayed significantly increased body weight, adipose tissue mass, and adipocyte cell size and reduced very low-density lipoprotein (VLDL) levels, as compared with littermate controls. These phenotypic alterations could not be explained by differences in feeding behavior, locomotor activity, metabolic energy expenditure, or adipose lipolysis. In addition, human adipocytes treated with either GSK126 or vehicle exhibited comparable rates of glucose-stimulated triglyceride accumulation and fatty acid uptake. Mechanistically, lipid accumulation induced by GSK126 in adipocytes was lipoprotein-dependent, and EZH2 inhibition or gene deletion promoted lipoprotein-dependent lipid uptake in vitro concomitant with up-regulated apolipoprotein E (ApoE) gene expression. Deletion of ApoE blocked the effects of GSK126 to promote lipoprotein-dependent lipid uptake in murine adipocytes. Collectively, these results indicate that EZH2 inhibition promotes lipoprotein-dependent lipid accumulation via inducing ApoE expression in adipocytes, suggesting a novel mechanism of lipid regulation by EZH2.


Assuntos
Adipócitos/metabolismo , Apolipoproteínas E/metabolismo , Diferenciação Celular , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Lipogênese , Lipólise , Adipócitos/citologia , Animais , Apolipoproteínas E/genética , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Humanos , Lipoproteínas VLDL/genética , Lipoproteínas VLDL/metabolismo , Camundongos , Regulação para Cima
20.
Artigo em Inglês | MEDLINE | ID: mdl-30931632

RESUMO

Studies have suggested that obesity is associated with better prognosis among individuals with various types of neurodegenerative diseases, and while some studies suggest that the same is true of amyotrophic lateral sclerosis (ALS), other works cast doubt on this conclusion. Therefore, we conducted a meta-analysis to systematically evaluate the role of body mass index in the prognosis of ALS. PubMed was systematically searched to identify eligible articles, and data on long-term survival were meta-analyzed in terms of hazard ratios (HR) with corresponding 95% confidence intervals (CI). Level of heterogeneity among studies and publication bias were estimated. A total of 17 studies with 9991 ALS patients were included in the review. Each increase of 1 kg/m2 in body mass index was associated with significantly better long-term overall survival (HR 0.95, 95%CI 0.93-0.97; p < 0.001). Obesity may also be a strong predictor of favorable long-term prognosis (HR 0.73; 95%CI 0.62-0.86; p < 0.001). Our results suggest that higher body mass index and obesity are associated with better long-term survival of ALS patients.

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