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1.
J Sep Sci ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31489796

RESUMO

A novel magnetic molecularly imprinted polymer adsorbing material was successfully synthesized to detect ribavirin in animal feedstuff. Molecularly imprinted polymer was prepared through surface polymerization by using ribavirin as template molecule, methyl methacrylate and γ-methacryloxypropyl trimethoxy silane functionalized magnetic mesoporous silica as bifunctional monomers, and ethylene diglycidyl ether as crosslinking agent. The prepared magnetic molecularly imprinted polymer was characterized by scanning electron microscopy and infrared spectroscopy. Static and dynamic adsorption experiments and selective adsorption analysis were performed to evaluate the adsorption and selectivity of magnetic molecularly imprinted polymer. Different experiments were conducted to optimize the magnetic solid-phase extraction conditions. Under optimal experimental conditions, a magnetic molecularly imprinted solid-phase extraction coupled with high-performance liquid chromatography method was successfully developed for ribavirin detection. The established method achieved a satisfactory linear range of 0.20-50.0 mg/L (R2 >0.99) and a low detection limit (0.081 mg/kg). An average recovery of 92.0%-105% with relative standard deviation of <6.5% was obtained upon the application of the developed method to detect ribavirin in real feedstuff samples. Thus, established method can be used for the rapid and simple separation and detection of added ribavirin in feedstuff. This article is protected by copyright. All rights reserved.

2.
Plant Biol (Stuttg) ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31464065

RESUMO

-Arbuscular mycorrhizal fungi (AMF) is an effective way to remove heavy metals' inhibition on plants, however, few relevant research attempts have been made to determine the contribution of AMF to the physiological and biochemical changes related to the enhanced copper tolerance of Phragmites australis under metal-stressed conditions. -In this study, the effects of AMF inoculation on P. australis under different concentrations of copper stress were investigated according to the changes in the parameters related to growth and development, and photosynthetic charateristics. Then, differentially expressed proteins (DEPs) were evaluated by the Isobaric Tag for Relative and Absolute Quantification (iTRAQ) system, which could accurately quantify the DEPs by measuring peak intensities of reporter ions in tandem mass spectrometry (MS/MS) spectra. -It was found that AMF inoculation may relieve the photosynthesis inhibition caused by copper stress on P. australis and thus promote growth. Proteomic analysis results showed that under copper stress, the inoculation of R. irregularis resulted in a total of 459 differently-expressed proteins (200 up-regulated and 259 down-regulated) in root buds. In addition, the photosynthetic changes caused by AMF inoculation mainly involve the up-regulated expression of transmembrane protein-pigment complexes CP43 (photosystem II) and FNR (ferredoxin-NADP+ oxidoreductase related to photosynthetic electron transport). -These results indicate that AMF could effectively improve the growth and physiological activity of P. australis under copper stress, and thus provides a new direction and instructive evidence for determining the mechanisms by which AMF inoculation enhances the copper tolerance of plants. This article is protected by copyright. All rights reserved.

3.
J Sci Food Agric ; 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31442313

RESUMO

BACKGROUND: excessive or improper use of organophosphorus pesticides (OPPs) may adversely affect human health through the food chain. In the present study, a simple, rapid, and effective analytical method was successfully established and used for the determination of OPPs quinalphos and its analogs in different food samples. RESULTS: under the optimized experimental conditions, five OPPs (quinalphos, triazophos, parathion, fenthion, and chlorpyrifos-methyl) exhibit a good linearity within a range of 0.02 to 2.0 µg/mL. The detection limit range was 3.0 to 10.0 µg/L (S/N=3). The method was successfully used to detect and quantify the residues of quinalphos and its analogs in tomato, cabbage, barley, and water samples; all spiked samples gave satisfactory recovery rates for the target analytes between 82% and 98%, with a relative standard deviation of 3.6% to 7.8%. CONCLUSION: results show that the proposed method is an accurate, rapid, and reliable sample pre-treatment method that gives a good enrichment factor and detection limit for determining quinalphos pesticide residues in different food samples. This article is protected by copyright. All rights reserved.

4.
Ann Bot ; 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31314080

RESUMO

BACKGROUND AND AIMS: Whole-genome duplication (WGD) events are considered important driving forces of diversification. At least 11 out of 52 Brassicaceae tribes had independent mesopolyploid WGDs followed by diploidization processes. However, the association between mesopolyploidy and subsequent diversification is equivocal. Herein we show the results from a family-wide diversification analysis on Brassicaceae, and elaborate on the hypothesis that polyploidization per se is a fundamental driver in Brassicaceae evolution. METHODS: We established a time-calibrated chronogram based on whole plastid genomes comprising representative Brassicaceae taxa and published data spanning the entire Rosidae clade. This allowed to set multiple calibration points and anchored various Brassicaceae taxa for subsequent downstream analyses. All major splits among Brassicaceae lineages were used in BEAST analyses of individually analysed 48 tribes comprising 2101 taxa in total using the internal transcribed spacers of nuclear ribosomal DNA. Diversification patterns were investigated on these tribe-wide chronograms using BAMM and were compared with family-wide data on genome size variation and species richness. KEY RESULTS: Brassicaceae diverged 29.9 Mya during the Oligocene, and the majority of tribes started diversification in the Miocene with an average crown group age of about 12.5 Mya. This matches the cooling phase right after the Mid Miocene climatic optimum. Significant rate shifts were detected in 12 out of 52 tribes during the Mio- and Pliocene, decoupled from preceding mesopolyploid WGDs. Among the various factors analysed the combined effect of tribal crown group age and net diversification rate (speciation minus extinction) is likely to explain sufficiently species richness across Brassicaceae tribes. CONCLUSIONS: The onset of the evolutionary splits among tribes took place under cooler and drier conditions. Pleistocene glacial cycles may have contributed to the maintenance of high diversification rates. Rate shifts are not consistently associated with mesopolyploid WGD. We propose, therefore, that WGDs in general serve as a constant "pump" for continuous and high species diversification.

5.
Nat Microbiol ; 4(8): 1378-1388, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31110366

RESUMO

Mycobacterium tuberculosis (Mtb)-derived components are usually recognized by pattern recognition receptors to initiate a cascade of innate immune responses. One striking characteristic of Mtb is their utilization of different type VII secretion systems to secrete numerous proteins across their hydrophobic and highly impermeable cell walls, but whether and how these Mtb-secreted proteins are sensed by host immune system remains largely unknown. Here, we report that MPT53 (Rv2878c), a secreted disulfide-bond-forming-like protein of Mtb, directly interacts with TGF-ß-activated kinase 1 (TAK1) and activates TAK1 in a TLR2- or MyD88-independent manner. MPT53 induces disulfide bond formation at C210 on TAK1 to facilitate its interaction with TRAFs and TAB1, thus activating TAK1 to induce the expression of pro-inflammatory cytokines. Furthermore, MPT53 and its disulfide oxidoreductase activity is required for Mtb to induce the host inflammatory responses via TAK1. Our findings provide an alternative pathway for host signalling proteins to sense Mtb infection and may favour the improvement of current vaccination strategies.

6.
Mol Phylogenet Evol ; 135: 177-184, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30858078

RESUMO

Stylommatophora is a main clade of Gastropoda that encompasses approximately 112 gastropod families and may exceed a total of 30,000 species. Twenty-four complete stylommatophoran mitogenomes have been sequenced to date, yet our understanding of mitochondrial evolution in stylommatophorans is still in its infancy. To further expand the set of available mitogenomes, we sequenced the mitogenome of Meghimatium bilineatum (Arionoidea: Philomycidae), a widespread land slug in East Asia. This is the first report on a mitogenome of the superfamily Arionoidea, and indeed on a terrestrial slug. The mitogenome of Meghimatium bilineatum comprises 13,972 bp and exhibits a novel, highly distinctive gene arrangement among the Stylommatophora. Phylogenetic reconstructions based on the sequences of all protein-coding genes consistently recovered Meghimatium bilineatum as sister-group of the Succineidae. A phylogenetic reconstruction based on gene order, however, suggested a highly divergent tree topology, which is less credible when taking into account prior knowledge of stylommatophoran relationships. Our CREx (Common interval Rearrangement Explorer) analysis suggested that three successive events of tandem duplication random loss (TDRL) best explain the evolutionary process of gene order rearrangement in Meghimatium bilineatum from an ancestral stylommatophoran mitogenome. The present example offers new insights into the mechanisms of mitogenome rearrangements in gastropods at large and into the usefulness of mitogenomic gene order as a phylogenetic marker.


Assuntos
Gastrópodes/genética , Rearranjo Gênico , Genoma Mitocondrial , Animais , Sequência de Bases , Mapeamento Cromossômico , Extremo Oriente , Ordem dos Genes , Mitocôndrias/genética , Filogenia
7.
Food Funct ; 10(2): 1049-1061, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30706921

RESUMO

The present study was designed to explore the neuroprotective effects of docosahexaenoic acid (DHA) and/or vitamin E (VE) in vitro. The PC12 cells were pretreated with DHA and/or VE for 4 h, followed by 50 µmol L-1 Aß25-35 treatments for another 48 h. The cells were then collected and used for the measurements of oxidative stress parameters. Real time-PCR and western blot were applied to measure fatty acid transporters, Nrf2 and its downstream antioxidant targets' gene and protein expression. Our results indicated that the Aß25-35 treatment inhibited cellular growth, increased intracellular ROS generation and decreased the mitochondrial membrane potential. The Aß25-35 treatment decreased the total antioxidant capacity (T-AOC), whereas it increased the MDA levels in neuron cells. Pretreatment of cells with VE or DHA could antagonize the Aß25-35-mediated cell growth inhibition and mitochondrial membrane potential decline. Activation of the Nrf2 signaling pathway and regulation of CD36, SRB1 and FABP5 expression were observed in DHA- and DHA + VE-pretreated cells. Our results indicated a synergistic effect of DHA and VE in antagonizing the oxidative damage caused by Aß25-35 in the PC12 cells. The results of the present study will shed light on the application of nutritional intervention for DHA and VE in preventing neuronal damage-related diseases.


Assuntos
Peptídeos beta-Amiloides/toxicidade , Ácidos Docosa-Hexaenoicos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Neurônios/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fragmentos de Peptídeos/toxicidade , Vitamina E/farmacologia , Animais , Antígenos CD36/genética , Antígenos CD36/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/administração & dosagem , Proteínas do Olho/genética , Proteínas do Olho/metabolismo , Proteínas de Transporte de Ácido Graxo/genética , Proteínas de Transporte de Ácido Graxo/metabolismo , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/genética , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Células PC12 , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Espécies Reativas de Oxigênio , Receptores Depuradores Classe B/genética , Receptores Depuradores Classe B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Vitamina E/administração & dosagem
8.
BMC Biol ; 17(1): 7, 2019 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-30683096

RESUMO

BACKGROUND: The emergence of drug-resistant strains of Mycobacterium tuberculosis (Mtb), especially those that are multidrug resistant poses a serious threat to global tuberculosis control. However, the mechanism underlying the occurrence of drug resistance against more than one drug is poorly understood. Given that the Beijing/W strains are associated with outbreaks and multidrug resistance, they may harbor a genetic advantage and provide useful insight into the disease. One marker found in all Beijing/W Mtb strains is a deletion of RD105 region that results in a gene fusion, Rv0071/74, with a variable number (3-9 m) of VDP (V: Val, D: Asp; P: Pro) repeats (coded by gtggacccg repeat sequences) at the N-terminal. Here, we report that this variable number of VDP repeats in Rv0071/74 regulates the development of multidrug resistance. RESULTS: We collected and analyzed 1255 Beijing/W clinical strains. The results showed that the number of VDP repeats in Rv0071/74 was related to the development of multidrug resistance, and the deletion of Rv0071/74-9 m from Beijing/W clinical strain restored drug susceptibility. Rv0071/74-9 m also increased resistance to multiple drugs when transferred to different mycobacterial strains. Cell-free assays indicate that the domain carrying 4-9 VDP repeats (4-9 m) showed a variable binding affinity with peptidoglycan and Rv0071/74 cleaves peptidoglycan. Furthermore, Rv0071/74-9 m increased cell wall thickness and reduced the intracellular concentration of antibiotics. CONCLUSIONS: These findings not only identify Rv0071/74 with VDP repeats as a newly identified multidrug resistance gene but also provide a new model for the development of multiple drug resistance.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Mycobacterium tuberculosis/genética , Deleção de Sequência , Genótipo , Mycobacterium tuberculosis/efeitos dos fármacos
9.
Cancer Med ; 8(3): 1135-1147, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30632714

RESUMO

The present study elucidates the potential role of Trop2 in tumor invasion and the promotion of epithelial-mesenchymal transition (EMT) when binding ß-catenin in GC. The role of Trop2 in promoting EMT in GC cells was examined by a variety of experimental assays. Moreover, the underlying molecular mechanism of Trop2 in promoting EMT was studied by in vivo and in vitro assays. The Trop2 expression in relation to tumor metastasis status was detected by IHC in 248 cases of GC tissues and 86 cases of matched adjacent tissues. Trop2 promoted the metastasis and induces EMT in GC. Meanwhile, the elevated protein levels of Trop2 and mesenchymal markers were also found in the TGF-ß1-induced EMT model in GC cells. Importantly, Trop2 physically bound and activated ß-catenin to promote EMT; moreover, Trop2 increased the accumulation of ß-catenin in the nucleus to accelerate metastasis in GC cells. Inhibition of Trop2 expression in GC cells prevented the migration and invasion of GC cells in vivo. Trop2+/vimentin+ expression was higher in GC tissues than that in matched adjacent tissues, and Trop2+/vimentin+ expression in GC was associated with the differentiation, TNM stage, and distant metastases. These sets of data reveal a novel regulatory network of Trop2 in EMT and GC metastasis, suggesting Trop2 as a useful marker for inducing EMT and metastasis of GC, which may help to lead a better understanding of the pathogenesis of the GC.

10.
Infect Genet Evol ; 72: 86-92, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30543940

RESUMO

Mycobacterium tuberculosis (MTB) infections rely on continued growth and division. Despite the substantial global burden of tuberculosis, the underlying mechanism governing growth is incompletely understood. Bifunctional penicillin-binding protein (PBP1), encoded by Rv0050 (ponA1) of MTB, is a key peptidoglycan synthase and plays a central role in mycobacterial growth and division by its interaction with Rpf-interacting protein A (RipA, peptidoglycan endopeptidase). Our previous work suggested that the hyper-variable proline repeats are located at the N end of PBP1. In this study, we prove that altered secondary structure resulting from polymorphic proline repeats modulates the interaction between PBP1 and RipA. Without proper coordination of peptidoglycan synthase and hydrolase, cell elongation and division is also altered resulting in phenotypic changes in the population as indicated by altered dispersion, slowed growth, or shortened cell length. Together, our data reveal that polymorphisms in Rv0050 induce mycobacterial growth and morphologic changes, and hence are responsible for giving bacteria their shape.

11.
Mol Phylogenet Evol ; 130: 45-59, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30308278

RESUMO

The Yangtze River Basin in China is one of the global hotspots of freshwater mussel (order Unionida) diversity with 68 nominal species. Few studies have tested the validity of these nominal species. Some taxa from the Yangtze unionid fauna have not been adequately examined using molecular data and well-positioned phylogenetically with respect to the global Unionida. We evaluated species boundaries of Chinese freshwater mussels, and disentangled their phylogenetic relationships within the context of the global freshwater mussels based on the multi-locus data and complete mitochondrial genomes. Moreover, we produced the time-calibrated phylogeny of Unionida and explored patterns of diversification. COI barcode data suggested the existence of 41 phylogenetic distinct species from our sampled 40 nominal taxa inhabiting the middle and lower reaches of the Yangtze River. Maximum likelihood and Bayesian inference analyses on three loci (COI, 16S, and 28S) and complete mitochondrial genomes showed that the subfamily Unioninae sensu stricto was paraphyletic, and the subfamily Anodontinae should be subsumed under Unioninae. In addition, we described two new tribes (Aculamprotulini tribe nov. and Lepidodesmini tribe nov.) in the subfamily Unioninae and one new genus (Parvasolenaiagen. nov.) in the subfamily Gonideinae. Molecular dating analysis suggested freshwater mussels diversified at 346.1 Mya (HPD = 286.6-409.9). The global diversification rate for Unionida was estimated to be 0.025 species/Myr. Our study found only a single well-supported rate shift in Unionida diversification, occurring at the base of the subfamily Ambleminae. The evolution of active host-attraction may have triggered the burst of speciation in Ambleminae, and the environment and geography of the Mississippi River Basin likely sustained this radiation.


Assuntos
Bivalves/classificação , Filogenia , Animais , Teorema de Bayes , Bivalves/genética , China , Complexo IV da Cadeia de Transporte de Elétrons/genética , Água Doce , Variação Genética , Genoma Mitocondrial/genética , RNA Ribossômico/genética , Especificidade da Espécie
12.
Aging (Albany NY) ; 10(12): 4066-4083, 2018 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-30573705

RESUMO

OBJECTIVE: The current study evaluated the relationship between circulating fat soluble vitamin status and cognition in aging Chinese population. METHODS: A cross-sectional study was carried out in 1754 community residents aged 55-80 years aiming to evaluate the relationship between circulating α-tocopherol and retinol status and cognition. The effect of ApoE genetic polymorphism on the relationship between vitamins and cognition was also explored. RESULTS: Our results indicated that serum retinol status positively correlated with cognitive performance; while, serum α-tocopherol (α-TOH)/retinol ratio negatively correlated with cognitive performance. Mild cognitive impairment (MCI) subject demonstrated higher serum α-TOH status (P < 0.05), α-TOH/retinol ratio (P < 0.01) and lower retinol status (P < 0.01) than normal subjects. Subjects with ApoE4 genotype have lower serum retinol level (P < 0.05) and higher α-TOH/retinol ratio (P < 0.01) than subjects with ApoE3 genotype. MCI-ApoE4 carriers demonstrated the worst cognitive performance (P < 0.05) and exhibited higher serum TC, α-TOH and α-TOH/retinol ratio levels (P < 0.05), and lower LDL-C, retinol and lipid-adjusted retinol status (P < 0.05). MCI-ApoE2 subjects showed higher serum TC, HDL-C content and α-TOH/retinol ratio (P < 0.05); and lower serum retinol and lipid-adjusted retinol status (P < 0.05). CONCLUSION: Lower circulating retinol and higher α-TOH/retinol ratio potentially predicts an increased risk for the development of cognitive decline in aging Chinese adults. ApoE2 or E4 carriers with higher circulating α-TOH/retinol ratio infer poor cognitive performance and an increased risk of developing MCI.

13.
Biol Sex Differ ; 9(1): 44, 2018 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-30305157

RESUMO

BACKGROUND: Worldwide tuberculosis (TB) reports show a male bias in morbidity; however, the differences in pathogenesis between men and women with TB, as well as the mechanisms associated with such differences, are poorly investigated. We hypothesized that comparison of the degree of lung injury and clinical indices of well-matched men and women with newly diagnosed TB, and statistical analysis of the correlation between these indices and the extent of lung lesions, can provide insights into the mechanism of gender bias in TB. METHODS: We evaluated the acid-fast bacilli grading of sputum samples and compiled computed tomography (CT) data of the age-matched, newly diagnosed male and female TB patients without history of smoking or comorbidities. Inflammatory biomarker levels and routine haematological and coagulation-associated parameters were compared. Binary logistic regression analysis was used to define the association between the indices and lung lesions, and the influence of sex adjustment. RESULTS: Women with TB have a longer delay in seeking healthcare than men after onset of the TB-associated symptoms. Men with TB have significantly more severe lung lesions (cavities and healing-associated features) and higher bacterial counts compared to women with TB. Scoring of the CT images before and after anti-TB treatment showed a faster response to therapy in women than in men. Coagulation- and platelet-associated indices were in models from multivariate regression analysis with groups of males or females with TB or in combination. In univariate regression analysis, lower lymphocyte counts were associated with both cavity and more bacterial counts, independent of sex, age and BMI. The association of international normalized ratios (INR), prothrombin times (PTs), mean platelet volumes (MPVs) and fibrinogen (FIB) level with lung lesions was mostly influenced by sex adjustment. CONCLUSIONS: Sex influences the association between haemostasis and extent of TB lung lesions, which may be one mechanism involved in sex bias in TB pathogenesis.

14.
Nat Commun ; 9(1): 4072, 2018 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-30287856

RESUMO

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), and remains a leading public health problem. Previous studies have identified host genetic factors that contribute to Mtb infection outcomes. However, much of the heritability in TB remains unaccounted for and additional susceptibility loci most likely exist. We perform a multistage genome-wide association study on 2949 pulmonary TB patients and 5090 healthy controls (833 cases and 1220 controls were genome-wide genotyped) from Han Chinese population. We discover two risk loci: 14q24.3 (rs12437118, Pcombined = 1.72 × 10-11, OR = 1.277, ESRRB) and 20p13 (rs6114027, Pcombined = 2.37 × 10-11, OR = 1.339, TGM6). Moreover, we determine that the rs6114027 risk allele is related to decreased TGM6 transcripts in PBMCs from pulmonary TB patients and severer pulmonary TB disease. Furthermore, we find that tgm6-deficient mice are more susceptible to Mtb infection. Our results provide new insights into the genetic etiology of TB.

15.
Nature ; 563(7729): 131-136, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30356214

RESUMO

Accurate repair of DNA double-stranded breaks by homologous recombination preserves genome integrity and inhibits tumorigenesis. Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that activates innate immunity by initiating the STING-IRF3-type I IFN signalling cascade1,2. Recognition of ruptured micronuclei by cGAS links genome instability to the innate immune response3,4, but the potential involvement of cGAS in DNA repair remains unknown. Here we demonstrate that cGAS inhibits homologous recombination in mouse and human models. DNA damage induces nuclear translocation of cGAS in a manner that is dependent on importin-α, and the phosphorylation of cGAS at tyrosine 215-mediated by B-lymphoid tyrosine kinase-facilitates the cytosolic retention of cGAS. In the nucleus, cGAS is recruited to double-stranded breaks and interacts with PARP1 via poly(ADP-ribose). The cGAS-PARP1 interaction impedes the formation of the PARP1-Timeless complex, and thereby suppresses homologous recombination. We show that knockdown of cGAS suppresses DNA damage and inhibits tumour growth both in vitro and in vivo. We conclude that nuclear cGAS suppresses homologous-recombination-mediated repair and promotes tumour growth, and that cGAS therefore represents a potential target for cancer prevention and therapy.

16.
Nat Commun ; 9(1): 4295, 2018 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-30327467

RESUMO

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) kills millions every year, and there is urgent need to develop novel anti-TB agents due to the fast-growing of drug-resistant TB. Although autophagy regulates the intracellular survival of Mtb, the role of calcium (Ca2+) signaling in modulating autophagy during Mtb infection remains largely unknown. Here, we show that microRNA miR-27a is abundantly expressed in active TB patients, Mtb-infected mice and macrophages. The target of miR-27a is the ER-located Ca2+ transporter CACNA2D3. Targeting of this transporter leads to the downregulation of Ca2+ signaling, thus inhibiting autophagosome formation and promoting the intracellular survival of Mtb. Mice lacking of miR-27a and mice treated with an antagomir to miR-27a are more resistant to Mtb infection. Our findings reveal a strategy for Mtb to increase intracellular survival by manipulating the Ca2+-associated autophagy, and may also support the development of host-directed anti-TB therapeutic approaches.

17.
Oncol Rep ; 40(5): 2906-2915, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30226548

RESUMO

Monocarboxylate transporter 4 (MCT4) is a membrane transporter of monocarboxylates that has been reported to play an important role in tumorigenesis and progression in several solid tumor types. The present study aimed to investigate its clinical significance in esophageal squamous cell carcinoma (ESCC). After obtaining and analyzing MCT4 mRNA expression data from The Cancer Genome Atlas (TCGA) database, the prognostic potential of MCT4 was evaluated by IHC analysis. The effect of the knockdown of MCT4 by shRNA was also evaluated using Cell Counting Kit-8 (CCK-8) and clonogenic assays, in order to determine whether MCT4 inhibition affected the proliferation and survival ability of ESCC cells. Flow cytometric analysis was used to evaluate apoptosis. Western blot analysis was performed to detect the expression levels of p-Akt, Bax, Bcl-2, cytoplasmic cytochrome c and cleaved caspase-3. MCT4 expression was associated with T stage (P=0.001), N stage (P=0.020) and formalin­fixed and paraffin-embedded (TNM) stage (P=0.042). Kaplan-Meier survival analysis indicated that patients in the high-MCT4 group had a lower overall survival (OS) rate (P=0.001) and progression-free survival (PFS) rate (P=0.003). The univariate Cox regression analysis and multivariate Cox regression analysis results indicated that MCT4 is an independent predictor of OS (P=0.001 and 0.014) and PFS (P=0.004 and 0.046). Downregulation of MCT4 inhibited cell proliferation and increased apoptosis in vitro. The proliferation rate and clone numbers were decreased and apoptotic rates were increased in the sh-MCT4 groups (all P<0.05). Furthermore, MCT4 knockdown reduced the activation of Akt and increased Bax/Bcl-2 ratios, cytochrome c release and caspase-3 cleavage (all P<0.05). Consequently, MCT4 could serve as a promising biomarker for ESCC to identify patients with poor prognosis.

18.
Wei Sheng Yan Jiu ; 47(3): 378-383, 2018 May.
Artigo em Chinês | MEDLINE | ID: mdl-30082002

RESUMO

OBJECTIVE: To evaluate the diet quality of the Chinese elderly using adjusted Chinese Diet Balance Index( DBI-07) and to explore the association between dietary patterns and blood glucose and lipid with the aiming to provide scientific basis and theoretical support for nutrition education intervention. METHODS: A total of 1158 participants aged 50-90 involved in this cross-sectional study. The subjects were randomly recruited from Nanyuan Community and Wulituo Community by posting small advertisements in 2013-2015. Questionnaires were used to collect the information of demographic characters. Food intake information was collected by food frequency questionnaire( FFQ) method, and the dietary quality was evaluated by DBI-07 scoring and evaluating system. Peripheral vein blood samples were collected for the measurement of general biochemical parameters. RESULTS: The overall dietary pattern of the aging adults was imbalance. The major problem of the elderly was insufficient intakes in vegetables, fruits, milk, soybean and animal derived food. There was significant difference in blood glucose and high density lipoprotein-cholesterol levels between the subjects with different dietary patterns( P < 0. 05). CONCLUSION: Imbalanced dietary pattern was detected of the elderly in Beijing. Balanced dietary pattern which is rich in vegetables & fruits, milk, soybean and moderate animal derived foods should be recommended to the elderly.

19.
J Sep Sci ; 41(19): 3806-3814, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30088342

RESUMO

A novel magnetic plasticizer molecularly imprinted polymer adsorbing material (MIP@mSiO2 -ß-CD@Fe3 O4 ) was successfully synthesized for the determination of six phthalic acid esters in water, milk, and wine samples. The molecularly imprinted polymers were prepared via precipitation polymerization and a surface molecular imprinting technique, using a cyclodextrin-modified magnetic meso-porous material (mSiO2 -ß-CD@Fe3 O4 ) as a magnetic supporter, dibutyl phthalate and butyl benzyl phthalate as the dual template molecules, methacrylic acid as the functional monomer, and ethyleneglycol dimethacrylate as the cross-linking agent. The polymers were characterized by scanning electron microscopy, IR spectroscopy, and X-ray powder diffraction. Thermogravimetric analysis and static and dynamic adsorption experiments were carried out to assay its stability and selectivity. Under optimal experimental conditions, a magnetic solid-phase extraction with MIP@mSiO2 -ß-CD@Fe3 O4 coupled to gas chromatography and mass spectrometry method was successfully developed for the determination of phthalic acid esters. The established method achieved a good linear range of 0.10∼8.00 µg/mL (R > 0.99) and a low detection limit within the range of 1.0∼5.0 µg/L. An average recovery rate of 80.2∼103% with relative standard deviation < 6.7% was obtained upon the application of the developed method to detect phthalic acid esters in actual aqueous samples.

20.
Environ Sci Technol ; 52(15): 8649-8658, 2018 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-30027739

RESUMO

Environmentally friendly and low-cost catalysts are important for the rapid mineralization of organic contaminants in powerful advanced oxidation processes (AOPs). In this study, we reported N-doped graphitic biochars (N-BCs) as low-cost and efficient catalysts for peroxydisulfate (PDS) activation and the degradation of diverse organic pollutants in water treatment, including Orange G, phenol, sulfamethoxazole, and bisphenol A. The biochars at high annealing temperatures (>700 °C) presented highly graphitic nanosheets, large specific surface areas (SSAs), and rich doped nitrogen. In particular, N-BC derived at 900 °C (N-BC900) exhibited the highest degradation rate, which was 39-fold and 6.5-fold of that on N-BC400 and pristine biochar, respectively, and the N-BC900 surpassed most popular metal or nanocarbon catalysts. Different from the radical-based oxidation in N-BC400/PDS via the persistent free radicals (PFRs), singlet oxygen and nonradical pathways (surface-confined activated persulfate-carbon complexes) were discovered to dominate the oxidation processes in N-BC900/PDS. Moreover, the adsorption of organics was determined to be the key step determining reaction rate, revealing that the pre-adsorption of reactants significantly accelerated the nonradical oxidation pathway. This study not only provides robust and cheap carbonaceous materials for environmental remediation but also enables the first insight into the graphitic biochar-based nonradical catalysis.

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