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1.
Microbiome ; 12(1): 177, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39300532

RESUMO

BACKGROUND: Intake of dietary fiber is associated with a reduced risk of inflammatory bowel disease. ß-Glucan (BG), a bioactive dietary fiber, has potential health-promoting effects on intestinal functions; however, the underlying mechanism remains unclear. Here, we explore the role of BG in ameliorating colitis by modulating key bacteria and metabolites, confirmed by multiple validation experiments and loss-of-function studies, and reveal a novel bacterial cross-feeding interaction. RESULTS: BG intervention ameliorates colitis and reverses Lactobacillus reduction in colitic mice, and Lactobacillus abundance was significantly negatively correlated with the severity of colitis. It was confirmed by further studies that Lactobacillus johnsonii was the most significantly enriched Lactobacillus spp. Multi-omics analysis revealed that L. johnsonii produced abundant indole-3-lactic acid (ILA) leading to the activation of aryl hydrocarbon receptor (AhR) responsible for the mitigation of colitis. Interestingly, L. johnsonii cannot utilize BG but requires a cross-feeding with Bacteroides uniformis, which degrades BG and produces nicotinamide (NAM) to promote the growth of L. johnsonii. A proof-of-concept study confirmed that BG increases L. johnsonii and B. uniformis abundance and ILA levels in healthy individuals. CONCLUSIONS: These findings demonstrate the mechanism by which BG ameliorates colitis via L. johnsonii-ILA-AhR axis and reveal the important cross-feeding interaction between L. johnsonii and B. uniformis. Video Abstract.


Assuntos
Bacteroides , Colite , Indóis , Lactobacillus johnsonii , beta-Glucanas , Animais , Indóis/metabolismo , Camundongos , Colite/microbiologia , Colite/terapia , beta-Glucanas/metabolismo , Bacteroides/metabolismo , Humanos , Lactobacillus johnsonii/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Camundongos Endogâmicos C57BL , Masculino , Modelos Animais de Doenças , Microbioma Gastrointestinal , Feminino , Lactobacillus/metabolismo
2.
Molecules ; 29(9)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38731530

RESUMO

Hydroformylation of olefins is widely used in the chemical industry due to its versatility and the ability to produce valuable aldehydes with 100% atom economy. Herein, a hybrid phosphate promoter was found to efficiently promote rhodium-catalyzed hydroformylation of styrenes under remarkably mild conditions with high regioselectivities. Preliminary mechanistic studies revealed that the weak coordination between the Rhodium and the P=O double bond of this pentavalent phosphate likely induced exceptional reactivity and high ratios of branched aldehydes to linear products.

3.
Clin Epigenetics ; 16(1): 42, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491513

RESUMO

BACKGROUND: Congenital heart disease (CHD) is a prevalent congenital cardiac malformation, which lacks effective early biological diagnosis and intervention. MicroRNAs, as epigenetic regulators of cardiac development, provide potential biomarkers for the diagnosis and treatment of CHD. However, the mechanisms underlying miRNAs-mediated regulation of cardiac development and CHD malformation remain to be further elucidated. This study aimed to explore the function of microRNA-20b-5p (miR-20b-5p) in cardiac development and CHD pathogenesis. METHODS AND RESULTS: miRNA expression profiling identified that miR-20b-5p was significantly downregulated during a 12-day cardiac differentiation of human embryonic stem cells (hESCs), whereas it was markedly upregulated in plasma samples of atrial septal defect (ASD) patients. Our results further revealed that miR-20b-5p suppressed hESCs-derived cardiac differentiation by targeting tet methylcytosine dioxygenase 2 (TET2) and 5-hydroxymethylcytosine, leading to a reduction in key cardiac transcription factors including GATA4, NKX2.5, TBX5, MYH6 and cTnT. Additionally, knockdown of TET2 significantly inhibited cardiac differentiation, which could be partially restored by miR-20b-5p inhibition. CONCLUSIONS: Collectively, this study provides compelling evidence that miR-20b-5p functions as an inhibitory regulator in hESCs-derived cardiac differentiation by targeting TET2, highlighting its potential as a biomarker for ASD.


Assuntos
Dioxigenases , MicroRNAs , Humanos , Diferenciação Celular , Dioxigenases/genética , DNA/metabolismo , Metilação de DNA , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo
4.
Nat Commun ; 14(1): 7740, 2023 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-38007572

RESUMO

Gut microbiota plays a key role in insulin resistance (IR). Here we perform a case-control study of Chinese adults (ChiCTR2200065715) and identify that Parabacteroides distasonis is inversely correlated with IR. Treatment with P. distasonis improves IR, strengthens intestinal integrity, and reduces systemic inflammation in mice. We further demonstrate that P. distasonis-derived nicotinic acid (NA) is a vital bioactive molecule that fortifies intestinal barrier function via activating intestinal G-protein-coupled receptor 109a (GPR109a), leading to ameliorating IR. We also conduct a bioactive dietary fiber screening to induce P. distasonis growth. Dendrobium officinale polysaccharide (DOP) shows favorable growth-promoting effects on P. distasonis and protects against IR in mice simultaneously. Finally, the reduced P. distasonis and NA levels were also validated in another human type 2 diabetes mellitus cohort. These findings reveal the unique mechanisms of P. distasonis on IR and provide viable strategies for the treatment and prevention of IR by bioactive dietary fiber.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Animais , Humanos , Camundongos , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fibras na Dieta
5.
Carbohydr Polym ; 316: 120986, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37321707

RESUMO

Intake of dietary fiber has been proven to have several beneficial effects in maintaining host homeostasis and health. Here, we investigated the effects of different fibers on gut microbiota and related metabolites in rats. Healthy rats were supplemented with guar gum, carrageenan, glucomannan, ß-glucan, arabinoxylan, apple pectin, xylan, arabinogalactan, and xanthan gum, and these dietary fibers exhibited commonality and specificity on gut microbiota and related metabolites. The abundance of Phascolarctobacterium, Prevotella, Treponema, Butyricimonas, Bacteroides, and Lactobacillus was selectively increased by different dietary fibers, whereas the abundance of Clostridium perfringens and Bacteroides fragilis were decreased by all of these fibers. Indole-3-lactic acid was significantly increased by ß-glucan treatment, indicating the relationship between indole-3-lactic acid and Lactobacillus. Furthermore, Some species from Bacteroides were validated to produce indole-3-lactic acid, indole-3-acetic acid, and kynurenine (such as B. fragilis, B. ovatus, B. thetaiotaomicron, and B. xylanisolvens). These results provide important information on dietary guidelines based on the modification of gut microecology.


Assuntos
Microbioma Gastrointestinal , beta-Glucanas , Ratos , Animais , Fibras na Dieta/metabolismo , Suplementos Nutricionais , Bacteroides/metabolismo , beta-Glucanas/farmacologia
6.
Org Lett ; 25(2): 410-415, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36629396

RESUMO

The formation of vicinal all-carbon quaternary stereocenters remains a formidable challenge. We report herein the synthesis of such highly congested structural dyads by copper-catalyzed decarboxylative propargylation between propargyl carbonates and indanone-based nucleophiles. The implementation of diphenylethylenediamine (DPEN)-based ligands is the key to success. A wide range of functional groups was tolerated, delivering the indanone-based spirolactones in good yields with high diastereo- and enantioselectivity. The mechanistic observations suggest the capability of the new copper complex to enable stereocontrolled addition to copper-allenylidene species.

7.
Plant Commun ; 4(3): 100507, 2023 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-36540022

RESUMO

Double haploid production is the most effective way to create true-breeding lines in a single generation. In Arabidopsis, haploid induction via mutation of the centromere-specific histone H3 (cenH3) has been shown when the mutant is outcrossed to the wild-type, and the wild-type genome remains in the haploid progeny. However, factors that affect haploid induction are still poorly understood. Here, we report that a mutant of the cenH3 assembly factor Kinetochore Null2 (KNL2) can be used as a haploid inducer when pollinated by the wild-type. We discovered that short-term temperature stress of the knl2 mutant increased the efficiency of haploid induction 10-fold. We also demonstrated that a point mutation in the CENPC-k motif of KNL2 is sufficient to generate haploid-inducing lines, suggesting that haploid-inducing lines in crops can be identified in a naturally occurring or chemically induced mutant population, avoiding the generic modification (GM) approach at any stage. Furthermore, a cenh3-4 mutant functioned as a haploid inducer in response to short-term heat stress, even though it did not induce haploids under standard conditions. Thus, we identified KNL2 as a new target gene for the generation of haploid-inducer lines and showed that exposure of centromeric protein mutants to high temperature strongly increases their haploid induction efficiency.


Assuntos
Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Haploidia , Temperatura , Centrômero/genética , Cinetocoros
8.
Mol Biol Evol ; 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35671323

RESUMO

KINETOCHORE NULL2 (KNL2) plays key role in the recognition of centromeres and new CENH3 deposition. To gain insight into the origin and diversification of the KNL2 gene, we reconstructed its evolutionary history in the plant kingdom. Our results indicate that the KNL2 gene in plants underwent three independent ancient duplications in ferns, grasses and eudicots. Additionally, we demonstrated that previously unclassified KNL2 genes could be divided into two clades αKNL2 and ßKNL2 in eudicots and γKNL2 and δKNL2 in grasses, respectively. KNL2s of all clades encode the conserved SANTA domain, but only the αKNL2 and γKNL2 groups additionally encode the CENPC-k motif. In the more numerous eudicot sequences, signatures of positive selection were found in both αKNL2 and ßKNL2 clades, suggesting recent or ongoing adaptation. The confirmed centromeric localization of ßKNL2 and mutant analysis suggests that it participates in loading of new CENH3, similarly to αKNL2. A high rate of seed abortion was found in heterozygous ßKNL2 plants and the germinated homozygous mutants did not develop beyond the seedling stage. Taken together, our study provides a new understanding of the evolutionary diversification of the plant kinetochore assembly gene KNL2, and suggests that the plant-specific duplicated KNL2 genes are involved in centromere and/or kinetochore assembly for preserving genome stability.

9.
Front Microbiol ; 13: 828990, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464970

RESUMO

Genomic information for bacteria within the genus Rahnella remains limited. Rahnella sp. JZ-GX1 was previously isolated from the Pinus massoniana rhizosphere in China and shows potential as a plant growth-promoting (PGP) bacterium. In the present work, we combined the GridION Nanopore ONT and Illumina sequencing platforms to obtain the complete genome sequence of strain JZ-GX1, and the application effects of the strain in natural field environment was assessed. The whole genome of Rahnella sp. JZ-GX1 comprised a single circular chromosome (5,472,828 bp, G + C content of 53.53%) with 4,483 protein-coding sequences, 22 rRNAs, and 77 tRNAs. Based on whole genome phylogenetic and average nucleotide identity (ANI) analysis, the JZ-GX1 strain was reidentified as R. victoriana. Genes related to indole-3-acetic acid (IAA), phosphorus solubilization, nitrogen fixation, siderophores, acetoin, 1-aminocyclopropane-1-carboxylate (ACC) deaminase, gamma-aminobutyric acid (GABA) production, spermidine and volatile organic compounds (VOCs) biosynthesis were present in the genome of strain JZ-GX1. In addition, these functions were also confirmed by in vitro experiments. Importantly, compared to uninoculated control plants, Pyrus serotina, Malus spectabilis, Populus euramericana (Dode) Guinier cv. "San Martino" (I-72 poplar) and Pinus elliottii plants inoculated with strain JZ-GX1 showed increased heights and ground diameters. These findings improve our understanding of R. victoriana JZ-GX1 as a potential biofertilizer in agriculture.

10.
Plant J ; 110(5): 1462-1475, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35352402

RESUMO

The meadowfoam family (Limnanthaceae) is one of the smallest and genomically underexplored families of the Brassicales. The Limnanthaceae harbor about seven species in the genus Limnanthes (meadowfoam) and Floerkea proserpinacoides (false mermaidweed), all native to North America. Because all Limnanthes and Floerkea species have only five chromosome pairs, i.e., a chromosome number rare in Brassicales and shared with Arabidopsis thaliana (Arabidopsis), we examined the Limnanthaceae genomes as a potential model system. Using low-coverage whole-genome sequencing data, we reexamined phylogenetic relationships and characterized the repeatomes of Limnanthaceae genomes. Phylogenies based on complete chloroplast and 35S rDNA sequences corroborated the sister relationship between Floerkea and Limnanthes and two major clades in the latter genus. The genome size of Limnanthaceae species ranges from 1.5 to 2.1 Gb, apparently due to the large increase in DNA repeats, which constitute 60-70% of their genomes. Repeatomes are dominated by long terminal repeat retrotransposons, while tandem repeats represent only less than 0.5% of the genomes. The average chromosome size in Limnanthaceae species (340-420 Mb) is more than 10 times larger than in Arabidopsis (32 Mb). A three-dimensional fluorescence in situ hybridization analysis demonstrated that the five chromosome pairs in interphase nuclei of Limnanthes species adopt the Rabl-like configuration.


Assuntos
Arabidopsis , Magnoliopsida , Arabidopsis/genética , Cromossomos , Hibridização in Situ Fluorescente , Interfase , Magnoliopsida/genética , Filogenia
11.
Crit Rev Food Sci Nutr ; 62(19): 5349-5371, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33591236

RESUMO

Food nutrients plays a crucial role in human health, especially in gastrointestinal (GI) health. The effect of food nutrients on human health mainly depends on the digestion and fermentation process in the GI tract. In vitro GI digestion and fermentation models had the advantages of reproducibility, simplicity, universality, and could integrally simulate the in vivo conditions to mimic oral, gastric, small intestinal and large intestinal digestive processes. They could not only predict the relationship among material composition, structure and digestive characteristics, but also evaluate the bioavailability of material components and the impact of digestive metabolites on GI health. This review systematicly summarized the current state of the in vitro simulation models, and made detailed descriptions for their applications, advantages and disadvantages, and specially their applications in food carbohydrates. In addition, it also provided the suggestions for the improvement of in vitro models and firstly proposed to establish a set of standardized methods of in vitro dynamic digestion and fermentation conditions for food carbohydrates, which were in order to further evaluate more effects of the nutrients on human health in future.


Assuntos
Digestão , Modelos Biológicos , Carboidratos , Fermentação , Trato Gastrointestinal/metabolismo , Humanos , Reprodutibilidade dos Testes
12.
Sheng Li Xue Bao ; 73(4): 559-570, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34405212

RESUMO

Prostaglandins are a class of poly-unsaturated fatty acids-derived bioactive lipids with important physiological function by binding to specific receptors. Prostaglandin receptors lack specific antibodies, which greatly impedes the research on our understanding of the signaling of prostaglandins. The aim of this study was to identify nine mouse lines with amino terminal (-NH2, -N) HA-tagged prostaglandin receptors by using the combination of artificial sperm and CRISPR-Cas9 technology. The guide RNA expression plasmid and labeled targeting vector plasmids were transferred into "artificial sperm cells". The "artificial sperm cells" containing labeled proteins were selected and injected into mouse oocytes, and implanted into pseudopregnant mice to obtain labeled mice. The genomic DNA of the prostaglandin receptor tagged mice was extracted, and the genotypes of mice were detected by PCR method. We also isolated mouse peritoneal macrophages to verify the protein expression of HA-labeled prostaglandin receptor by Western blot. Specific DNA bands were amplified in prostaglandin receptor labeled mice, and specific HA protein bands were detected in macrophage proteins, which was not detected in wild type mice. In summary, we successfully constructed 9 mouse lines with HA-tagged prostaglandin receptors, providing a powerful tool for further study of the pathophysiological functions of prostaglandin signaling both in vivo and in vitro.


Assuntos
RNA Guia de Cinetoplastídeos , Receptores de Prostaglandina , Animais , Camundongos , Oócitos , Plasmídeos
13.
J Agric Food Chem ; 69(25): 7000-7015, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34139119

RESUMO

High intake of dietary fibers was found to be inversely associated with type-2 diabetes (T2D), whereas the difference among different dietary fibers on T2D remains unclear. Therefore, we have investigated the effects of different dietary fibers on T2D. Nine types of dietary fibers were used to investigate and evaluate their effects on type-2 diabetic rats via physiology, genomics, and metabolomics. We found that supplementation with ß-glucan, arabinogalactan, guar gum, apple pectin, glucomannan, and arabinoxylan significantly reduced the fasting blood glucose, whereas carrageenan, xylan, and xanthan gum did not affect glycemic control in diabetic rats. Also, bioactive dietary fibers (ß-glucan, arabinogalactan, guar gum, and apple pectin) associated with the increased butyric acid level and abundance of beneficial bacteria (Lachnobacterium, Parabacteroides, Faecalibacterium, Akkermansia, and some butyric acid-producing bacteria), as well as improved host metabolism by decreasing 12α-hydroxylated bile acids, acylcarnitines, and amino acids (leucine, phenylalanine, citrulline, etc.), thereby exert beneficial effects on T2D. It was also found that ß-glucan might attenuate insulin resistance via downregulation of Prevotella copri-mediated biosynthesis of branched-chain amino acids in T2D. Together, our study uncovered the effects of different dietary fibers on T2D, along with their potential mechanism.


Assuntos
Diabetes Mellitus Experimental , Microbioma Gastrointestinal , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Fibras na Dieta , Hipoglicemiantes , Prevotella , Ratos
14.
Int J Biol Macromol ; 154: 25-30, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32171833

RESUMO

The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied. Six legume polysaccharides' antidiabetic function in high-fat diet and streptozotocin-induced type II diabetic mice were compared. Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested. Results showed that red kidney bean polysaccharides (RK) could alleviate the symptoms of emaciation, decreased the levels of FBG, GSP, TC, LDL-c and obviously reduced the concentration of TG and HOMA-IR (p < 0.05). RK exhibited greater antidiabetic potential in type II diabetic mice, compared with other legume polysaccharides. The chemical composition of six legume polysaccharides were determined. Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition. Results indicated that the antidiabetic activities of RK might due to its higher content and specific structure of polysaccharide.


Assuntos
Fabaceae/química , Hipoglicemiantes/farmacologia , Polissacarídeos/farmacologia , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Jejum/sangue , Hipoglicemiantes/uso terapêutico , Insulina/sangue , Lipídeos/sangue , Masculino , Camundongos , Polissacarídeos/uso terapêutico
15.
Food Funct ; 11(4): 2886-2897, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32186298

RESUMO

This work investigated the physiochemical characteristics and preventive effects of purified pectin (H121, L13 and L102) with different esterification degrees on dextran sulfate sodium (DSS)-induced colitis in mice. Three doses of each type of pectin were administered to C57BL/6J mice for 7 days before the DSS treatment, with dextran and mesalazine as positive controls. Results showed that pathological factors including the body weight, the disease activity index (DAI), the colonic weight/length ratio and the organ index of the spleen were improved with pre-intervention of a high dose of L13 or L102. Further studies showed that administration of a low dose of L13, low dose and medium dose of L102 or dextran improved intestinal permeability and tight junction function in colitis mice. Treatments of L13 of all doses and L102 of a high dose downregulated the oxidative stress-associated factors, while L102 of a low dose and H121 ameliorated the inflammatory cytokine production in serum and the colon. The above results suggested that pectin could attenuate DSS-induced intestinal epithelial injury, inflammation and oxidative stress. Specifically, compared to high esterified pectin, low esterified pectin displayed better protective effects in acute colitis mice.


Assuntos
Colite Ulcerativa/prevenção & controle , Alimento Funcional , Pectinas/administração & dosagem , Administração Oral , Animais , Colite Ulcerativa/induzido quimicamente , Dextranos , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Organismos Livres de Patógenos Específicos
16.
Can Respir J ; 2019: 2697376, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379980

RESUMO

Aim: The transmembrane chemokine (C-X-C motif) ligand 16 (CXCL16) plays a vital role in the pathogenesis of organ fibrosis, including the liver and kidney. However, the detailed biological function of CXCL16 is still not fully understood in the progression of pulmonary fibrosis (PF). The aim of present study is to examine the function of CXCL16 in PF. Materials and Methods: In this study, we constructed the PF model on mouse by using bleomycin and analyzed the effect of the mouse recombinant protein CXCL16 on mouse lung fibroblast L929 (LF) as well. To further examine the connection between CXCL16 and STAT3 in mouse LF cells, the STAT3 inhibitor AG490 was utilized to inhibit the expression of STAT3. Meanwhile, lipopolysaccharide was used to enhance the phosphorylation of STAT3 (p-STAT3) in mouse LF cells. Results: Our results indicated that the level of CXCL16/CXCR6 was significantly upregulated in the mouse PF model. Moreover, the level of p-STAT3 was also promoted. In addition, the mouse recombinant protein CXCL16 not only contributed to the proliferation of mouse LF cells but also induced the expression of p-STAT3 in LF cells. However, the effect of CXCL16 was deeply abolished by the STAT3 inhibitor AG490 in LF cells. Meanwhile, the antibody of CXCL16 deeply reduced the phosphorylation of STAT3 in lipopolysaccharide (LPS) cultured cells. Conclusions: All these results demonstrated that CXCL16 promoted the phosphorylation of STAT3 and further demonstrated that STAT3 was a critical component in CXCL16/CXCR6 signaling pathway. This research not only enhanced the comprehension of CXCL16 but also indicated its potential value as a target in the treatment for human PF.


Assuntos
Quimiocina CXCL16/sangue , Modelos Animais de Doenças , Fibrose Pulmonar/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Estudos de Casos e Controles , Linhagem Celular , Progressão da Doença , Lipopolissacarídeos , Masculino , Camundongos , Fosforilação , Fator de Transcrição STAT3/antagonistas & inibidores , Tirfostinas
17.
Biomaterials ; 195: 75-85, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30616030

RESUMO

Targeted drug delivery with precisely controlled drug release and activation is highly demanding and challenging for tumor precision therapy. Herein, a biomimetic cascade nanoreactor (designated as Mem@GOx@ZIF-8@BDOX) is constructed for tumor targeted starvation therapy-amplified chemotherapy by assembling tumor cell membrane cloak and glucose oxidase (GOx) onto zeolitic imidazolate framework (ZIF-8) with the loading prodrug of hydrogen peroxide (H2O2)-sensitive BDOX. Biomimetic membrane camouflage affords superior immune evasion and homotypic binding capacities, which significantly enhance the tumor preferential accumulation and uptake for targeted drug delivery. Moreover, GOx-induced glycolysis would cut off glucose supply and metabolism pathways for tumor starvation therapy with the transformation of tumor microenvironments. Importantly, this artificial adjustment could trigger the site-specific BDOX release and activation for cascade amplified tumor chemotherapy regardless of the complexity and variability of tumor physiological environments. Both in vitro and in vivo investigations indicate that the biomimetic cascade nanoreactor could remarkably improve the therapeutic efficacy with minimized side effects through the synergistic starvation therapy and chemotherapy. This biomimetic cascade strategy would contribute to developing intelligent drug delivery systems for tumor precision therapy.


Assuntos
Biomimética/métodos , Nanopartículas/química , Animais , Glucose Oxidase/química , Humanos , Peróxido de Hidrogênio/química , Estruturas Metalorgânicas , Pró-Fármacos/química , Zeolitas/química
18.
Plant J ; 93(6): 1088-1101, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29381236

RESUMO

Brachypodium distachyon is a well-established model monocot plant, and its small and compact genome has been used as an accurate reference for the much larger and often polyploid genomes of cereals such as Avena sativa (oats), Hordeum vulgare (barley) and Triticum aestivum (wheat). Centromeres are indispensable functional units of chromosomes and they play a core role in genome polyploidization events during evolution. As the Brachypodium genus contains about 20 species that differ significantly in terms of their basic chromosome numbers, genome size, ploidy levels and life strategies, studying their centromeres may provide important insight into the structure and evolution of the genome in this interesting and important genus. In this study, we isolated the centromeric DNA of the B. distachyon reference line Bd21 and characterized its composition via the chromatin immunoprecipitation of the nucleosomes that contain the centromere-specific histone CENH3. We revealed that the centromeres of Bd21 have the features of typical multicellular eukaryotic centromeres. Strikingly, these centromeres contain relatively few centromeric satellite DNAs; in particular, the centromere of chromosome 5 (Bd5) consists of only ~40 kb. Moreover, the centromeric retrotransposons in B. distachyon (CRBds) are evolutionarily young. These transposable elements are located both within and adjacent to the CENH3 binding domains, and have similar compositions. Moreover, based on the presence of CRBds in the centromeres, the species in this study can be grouped into two distinct lineages. This may provide new evidence regarding the phylogenetic relationships within the Brachypodium genus.


Assuntos
Brachypodium/genética , Centrômero/genética , DNA de Plantas/genética , Genoma de Planta/genética , Sequência de Aminoácidos , Brachypodium/classificação , Brachypodium/metabolismo , Centrômero/metabolismo , Cromossomos de Plantas/genética , Cromossomos de Plantas/metabolismo , DNA de Plantas/metabolismo , Evolução Molecular , Histonas/genética , Histonas/metabolismo , Hibridização in Situ Fluorescente , Nucleossomos/genética , Nucleossomos/metabolismo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Poliploidia , Ligação Proteica , Homologia de Sequência de Aminoácidos
19.
Sci Rep ; 7: 41659, 2017 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-28134354

RESUMO

Sugarcane (Saccharum hybrids spp.) is the most important sugar crop that accounts for ~75% of the world's sugar production. Recently, a whole-genome sequencing project was launched on the wild species S. spontaneum. To obtain information on the DNA composition of the repeat-enriched region of the centromere, we conducted a genome-wide analysis of the DNA sequences associated with CenH3 (a mutant of histone H3 located in eukaryote centromeres) using chromatin immunoprecipitation followed by sequencing (ChIP-seq) method. We demonstrate that the centromeres contain mainly SCEN-like single satellite repeat (Ss1) and several Ty3/gypsy retrotransposon-related repeats (Ss166, Ss51, and Ss68). Ss1 dominates in the centromeric regions and spans up to 500 kb. In contrast, the Ty3/gypsy retrotransposon-related repeats are either clustered spanning over a short range, or dispersed in the centromere regions. Interestingly, Ss1 exhibits a chromosome-specific enrichment in the wild species S. spontaneum and S. robustum, but not in the domesticated species S. officinarum and modern sugarcane cultivars. This finding suggests an autopolyploid genome identity of S. spontaneum with a high level of homology among its eight sub-genomes. We also conducted a genome-wide survey of the repetitive DNAs in S. spontaneum following a similarity-based sequence clustering strategy. These results provide insight into the composition of sugarcane genome as well as the genome assembly of S. spontaneum.


Assuntos
Centrômero/genética , Genoma de Planta , Sequências Repetitivas de Ácido Nucleico , Saccharum/genética , Elementos de DNA Transponíveis , Histonas/genética , Ploidias
20.
BMC Pulm Med ; 16(1): 124, 2016 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-27544078

RESUMO

BACKGROUND: Autonomic dysfunction in patients with chronic obstructive pulmonary disease (COPD) may increase the risks of arrhythmia and sudden death. We studied cardiac autonomic function in patients with acute exacerbation of COPD (AECOPD). METHODS: Patients with AECOPD were classified into ventricular tachycardia (VT) and non-VT groups according to the presence or absence of VT. The following parameters derived from 24-h Holter monitoring were compared between groups: average heart rate, heart rate deceleration capacity (DC), heart rate acceleration capacity (AC), standard deviation of normal RR intervals (SDNN), standard deviation of average RR interval in 5-min segments (SDANN), root mean square of standard deviations of differences between adjacent normal RR intervals (rMSSD), low-frequency power (LF), high-frequency power (HF) and LF/HF ratio. RESULTS: Seventy patients were included, 22 in the VT group and 48 in the non-VT group. The groups had similar clinical characteristics (except for more common amiodarone use in the VT group, P < 0.05) and general ECG characteristics. DC, SDNN, SDANN and rMSSD were lower and AC higher in the VT group (P < 0.05). In the VT group, DC was correlated positively with SDNN (r = 0.716), SDANN (r = 0.595), rMSSD (r = 0.571) and HF (r = 0.486), and negatively with LF (r = -0.518) and LF/HF (r = -0.458) (P < 0.05). AC was correlated negatively with SDNN (r = -0.682), SDANN (r = -0.567) and rMSSD (r = -0.548) (P < 0.05). CONCLUSIONS: DC decreased and AC increased in patients with AECOPD and VT, reflecting an imbalance in autonomic regulation of the heart that might increase the risk of sudden death.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Coração/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/complicações , Taquicardia Ventricular/fisiopatologia , Doença Aguda , Idoso , China , Progressão da Doença , Eletrocardiografia Ambulatorial , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taquicardia Ventricular/complicações
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