Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 219
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Nanotechnology ; 31(16): 165704, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-31891932

RESUMO

Recently, Bi2O2Se was revealed as a promising two-dimensional (2D) semiconductor for next generation electronics, due to its moderate bandgap size, high electron mobility and pronounced ambient stability. Meanwhile, it has been predicted that high-quality Bi2O2Se-related heterostructures may possess exotic physical phenomena, such as piezoelectricity and topological superconductivity. Herein, we report the first successful heteroepitaxial growth of Bi2O2Se films on SrTiO3 substrates via pulsed laser deposition (PLD) method. Films obtained under optimal conditions show an epitaxial growth with the c axis perpendicular to the film surface and the a and b axes parallel to the substrate. The growth mode transition to three-dimensional (3D) island from quasi-2D layer of the heteroepitaxial Bi2O2Se films on SrTiO3 (001) substrates is observed as prolonging deposition time of films. The maximum value of electron mobility reaches 160 cm2 V-1 s-1 at room temperature in a 70 nm thick film. The thickness dependent mobility provides evidence that interface-scattering is likely to be the limiting factor for the relatively low electron mobility at low temperature, implying that the interface engineering as an effective method to tune the low temperature electron mobility. Our work suggests the epitaxial Bi2O2Se films grown by PLD are promising for both fundamental study and practical applications.

2.
Biochemistry ; 59(2): 132-138, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31592657

RESUMO

Methionine is one of the most hydrophobic, redox-sensitive, and one of the only two sulfur-containing amino acids on protein. Because of these biochemical properties, the methionine residue plays a central role in a variety of biological processes, such as metal coordination, antioxidant stress, and aging. However, studies on the molecular functions of methionine are much less common than the other primary sulfur-containing amino acid, cysteine. The limited number of publications on methionine-related studies is partially due to the lack of tools for methionine modification. Methionine bioconjugation offers a new strategy to decipher the biological function of methionine and expands the toolbox for protein functionalization in the context of the application, such as synthesizing proteins with novel properties and producing new biomaterials. The purpose of this Perspective is to highlight the biochemical properties and functions of methionine, list recent progress in the development of methionine bioconjugation reagents, and briefly demonstrate the application of these reagents on polypeptides, proteins, and proteomes.

3.
ACS Nano ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31789500

RESUMO

The ability of antibodies to bind a wide variety of analytes with high specificity and high affinity makes them ideal candidates for therapeutic and diagnostic applications. However, the poor stability and high production cost of antibodies have prompted exploration of a variety of synthetic materials capable of specific molecular recognition. Unfortunately, it remains a fundamental challenge to create a chemically diverse population of protein-like, folded synthetic nanostructures with defined molecular conformations in water. Here we report the synthesis and screening of combinatorial libraries of sequence-defined peptoid polymers engineered to fold into ordered, supramolecular nanosheets displaying a high spatial density of diverse, conformationally constrained peptoid loops on their surface. These polyvalent, loop-functionalized nanosheets were screened using a homogeneous Förster resonance energy transfer (FRET) assay for binding to a variety of protein targets. Peptoid sequences were identified that bound to the heptameric protein, anthrax protective antigen, with high avidity and selectivity. These nanosheets were shown to be resistant to proteolytic degradation, and the binding was shown to be dependent on the loop display density. This work demonstrates that key aspects of antibody structure and function-the creation of multivalent, combinatorial chemical diversity within a well-defined folded structure-can be realized with completely synthetic materials. This approach enables the rapid discovery of biomimetic affinity reagents that combine the durability of synthetic materials with the specificity of biomolecular materials.

4.
Medicine (Baltimore) ; 98(50): e18173, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852073

RESUMO

RATIONALE: Coronary artery aneurysms (CAAs) are uncommon in patients with acute coronary syndrome (ACS). We describe the clinical features and outcomes of stent-assisted coil embolization of a CAA in the trigeminal position. PATIENT CONCERNS: We present a 73-year-old woman with a history of paroxysmal episodes of precordial pain since 1 year. Coronary computed tomography angiography (CTA) revealed an aneurysm (diameter: 9 mm) at the junction of the distal left main coronary artery and the anterior descending branch. Troponin I, CK-MB, creatinine and routine blood investigations were within the normal range. DIAGNOSIS: Coronary artery aneurysm in the left main trigeminal position. INTERVENTIONS: The patient was treated with stent-assisted coil embolization. OUTCOMES: After complete filling of the aneurysm with coil, the microcatheter was withdrawn and the stent released in the descending branch. Two stents were successfully implanted. LESSONS: There is no clear consensus on the optimal therapy for patients with CAAs. Clinicians should be aware of the possible complications of stent-assisted coil embolization of CAA in the main trunk of the coronary artery.


Assuntos
Implante de Prótese Vascular/métodos , Aneurisma Coronário/terapia , Estenose Coronária/cirurgia , Vasos Coronários/diagnóstico por imagem , Embolização Terapêutica/métodos , Stents , Idoso , Angiografia Digital , Aneurisma Coronário/complicações , Aneurisma Coronário/diagnóstico , Angiografia Coronária , Estenose Coronária/complicações , Estenose Coronária/diagnóstico , Vasos Coronários/cirurgia , Feminino , Humanos , Doenças Raras
5.
Animals (Basel) ; 9(12)2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31775375

RESUMO

With increasing age, the rumen microbiota of new-born ruminants become central in the translation of fibrous feed substances into essential nutrients. However, the colonization process of the microbial community (especially fungal community) remains poorly understood in ruminants at pre-weaning stages. In this study, the rumen bacterial and fungal colonization processes were investigated in goats at eight stages using amplicon sequencing. For bacteria, we found 36 common core genera at D0, D3, D14, D28, and D56, including mainly Bacillus, Alloprevotella, Bacteroides, Prevotella_1, Lactococcus, and Ruminococcaceae_NK4A214. Firmicutes was the dominant phylum among the total microbiota in newborn goat kids (prior to nursing), while Bacillus, Lactococcus, and Pseudomonas were predominant genera. Interestingly, the proportion of Bacillus was as high as 55% in newborn animals. After milk nursing, the predominant phylum changed to Bacteroidetes, while the proportion of Bacillus and Lactobacillus was very low. CowPi was used to predict the functional gene pathways and we found increases in the abundance of genes associated with amino acid related enzymes, DNA repair and recombination proteins, aminoacyl tRNA biosynthesis, and peptidases after D3. With regard to fungi, we found that there were 51 common genera at day 0 (D0), D3, D14, D28, and D56, including mainly Cryptococcus, Aspergillus, and Caecomyces. Aspergillus occupied approximately 47% at day 0, but then it decreased from day 3 to day 14. This study indicates that the core microbes of rumen emerged shortly after birth, but the abundance was very different from the core genus of the adult rumen. In addition, we also report a detailed scheme of the bacterial and fungal colonization process in rumens and propose three distinct stages during the rumen colonization process in pre-weaning goats, which will offer a reference for the development of milk substitutes for small ruminants.

6.
Dalton Trans ; 48(46): 17395-17401, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31742278

RESUMO

The iron(iii) affinity constants for schizokinen and its imide derivative are reported for the first time. Surprisingly, schizokinen possesses a higher affinity for iron(iii) than desferrioxamine B; log KFeIII (FeL), 36.2 and 30.6, respectively. This increase in value is associated with the substitution of one hydroxamate function by an α-hydroxycarboxylate grouping. By virtue of the similarity of siderophore-iron(iii) complexes and siderophore-gallium(iii) complexes, schizokinen (which is a Gram positive siderophore) has potential for 68Ga PET-based imaging.

7.
Biosci Rep ; 39(11)2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664454

RESUMO

Microvesicles (MVs) were involved in the pathogenesis of many diseases, such as cardiovascular diseases and diabetes. Oxidative stress played a key role in the development and progression of diabetic nephropathy (DN). Our aim of the present study was to investigate whether high glucose (HG) could provoke MVs generation from podocytes and its potential mechanism. Mouse podocyte clone 5 (MPC-5) was stimulated by HG. The intracellular reactive oxygen species (ROS) of podocytes were measured by fluorescence microscopy with the probe of CM-H2DCFDA and MitoSOX™. Antioxidants N-Acetyl-l-cysteine (NAC) and α lipoic acid (α-LA) were used to treat podocytes after HG stimulation. The rate of podocyte apoptosis was evaluated with Annexin V-FITC by flow cytometry. NOX4 expression was examined and siRNA were performed to explore the mechanism of MVs generation. The quantities of MVs from MPC-5 cells was significantly increased (P<0.05) by 4.6-times after 30 mM glucose stimulation, accompanied with double increased apoptosis. Cellular ROS generation was increased by HG at the peak of 48 h stimulation. HG-induced MVs were significantly decreased by 52.9% after pretreatment by antioxidant NAC. Nevertheless, mitochondrial ROS in podocytes reached a peak at 4 h stimulation, but specific antioxidant α-LA had no effect on the production of MVs (P>0.05). Levels of NOX4 mRNA and protein expression were significantly up-regulated by HG (P<0.05). Podocyte-derived MVs by HG were eliminated by NOX4 siRNA. HG can provoke MVs generation from glomerular podocytes through ROS/NOX4 pathway, not from mitochondrial pathway.

8.
Front Microbiol ; 10: 2125, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31572331

RESUMO

Bacterial communities in gastrointestinal tracts (GIT) play an important role in animal health and performance. Despite its importance, little information is available on the establishment of microbial populations in the goat GIT or on changes occurring during early development. Therefore, this study investigated the bacterial community dynamics of the rumen, duodenum, jejunum, ileum, cecum, and colon in 15 goats at five developmental stages (0, 14, 28, 42, and 56 days old) by using 16S rDNA sequencing and quantitative real-time PCR technology. 940 genera were found to belong to 44 phyla distributed along the GIT. As a whole, the microbial richness and diversity showed a clear increasing trend as the kids aged and alpha diversity differed significantly among GIT compartments mainly occurring at middle day ages (14 and 28 days). Principal coordinate analysis indicated that the bacterial community displayed distinct temporal and spatial specificity along the GIT in preweaning goats. As kids aged, the phylum Firmicutes was replaced by Bacteroidetes in rumen, whereas Proteobacteria in the large intestine was displaced by Firmicutes. The phylum Proteobacteria was mainly present in the small intestine in older animals. In the rumen, taxa, such as Bacillus and Lactococcus decreased and Prevotella, Treponema, Ruminococcus, and unclassified Prevotellaceae increased with the age of kids. Furthermore, a lower proportion of taxa, such as Lactobacillus and Bacteroides was observed with higher abundances of both Christensenellaceae_R_7 and Ruminococcus in duodenum and jejunum in older animals. In the large intestine, the microbiota displayed taxonomic dynamics with increases of Ruminococcaceae UCG 005, unclassified Lachnospiraceae, Barnesiella, and Blautia as kids aged. Predicted pathway analysis suggested that genes involved in amino acid metabolism, and translation were abundant in both rumen and duodenum, while genes involved in membrane transport and carbohydrate metabolism were enriched in the large intestine. These results indicate that both the microbial colonization process and potential function exert a temporal-spatial specificity throughout the GIT of goats. This study provides new insight into the temporal dynamics of GIT microbiota development during preweaning and will aid to develop strategies for improving animal health and downstream production.

9.
Front Genet ; 10: 750, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31552084

RESUMO

Sheep and goats are valuable livestock species that have been raised for their production of meat, milk, fiber, and other by-products. Due to their suitable size, short gestation period, and abundant secretion of milk, sheep and goats have become important model animals in agricultural, pharmaceutical, and biomedical research. Genome engineering has been widely applied to sheep and goat research. Pronuclear injection and somatic cell nuclear transfer represent the two primary procedures for the generation of genetically modified sheep and goats. Further assisted tools have emerged to enhance the efficiency of genetic modification and to simplify the generation of genetically modified founders. These tools include sperm-mediated gene transfer, viral vectors, RNA interference, recombinases, transposons, and endonucleases. Of these tools, the four classes of site-specific endonucleases (meganucleases, ZFNs, TALENs, and CRISPRs) have attracted wide attention due to their DNA double-strand break-inducing role, which enable desired DNA modifications based on the stimulation of native cellular DNA repair mechanisms. Currently, CRISPR systems dominate the field of genome editing. Gene-edited sheep and goats, generated using these tools, provide valuable models for investigations on gene functions, improving animal breeding, producing pharmaceuticals in milk, improving animal disease resistance, recapitulating human diseases, and providing hosts for the growth of human organs. In addition, more promising derivative tools of CRISPR systems have emerged such as base editors which enable the induction of single-base alterations without any requirements for homology-directed repair or DNA donor. These precise editors are helpful for revealing desirable phenotypes and correcting genetic diseases controlled by single bases. This review highlights the advances of genome engineering in sheep and goats over the past four decades with particular emphasis on the application of CRISPR/Cas9 systems.

10.
Phys Rev Lett ; 123(4): 047203, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31491273

RESUMO

The recent discovery of intrinsic ferromagnetic order in the atomically thin van der Waals crystal CrXTe_{3} (X=Si, Ge) stimulates intensive studies on the nature of low-dimensional magnetism because the presence of long-range magnetic order in two-dimensional systems with continuous symmetry is strictly prohibited by thermal fluctuations. By combining advanced many-body calculations with angle-resolved photoemission spectroscopy we investigate CrSiTe_{3} single crystals and unveil the pivotal role played by the strong electronic correlations at both high- and low-temperature regimes. Above the Curie temperature (T_{c}), Coulomb repulsion (U) drives the system into a charge transfer insulating phase. In contrast, below T_{c} the crystal field arranges the Cr-3d orbitals such that the ferromagnetic superexchange profits, giving rise to the bulk ferromagnetic ground state with which the electronic correlations compete. The excellent agreement between theory and experiment establishes CrSiTe_{3} as a prototype low-dimensional crystal with the cooperation and interplay of electronic correlation and ferromagnetism.

11.
Sci Total Environ ; 696: 133955, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31446286

RESUMO

Palygorskite (Pal) is a natural abundant environment-friendly adsorbent that has shown high efficiency to decontaminate dye in water. However, the dye removal results in transformation of Pal to a very stable Maya Blue-like structure or waste Pal clay (WPal), which could not be easily regenerated by a commonly used desorption process. This paper presents a use of WPal as the precursor material to synthesize a highly-efficient mesoporous silicate/carbon composite adsorbent. The composite adsorbent has a large specific surface area (427.9 m2·g-1), a high negative potential (-40.6 mV) and a mesoporous size (3.48 nm). This adsorbent shows almost complete removal of tetracycline (TC), crystal violet (CV) and methylene blue (MB) (initial concentration, 200 mg·L-1) with the optimal adsorption capacities of 319.8 mg·g-1, 244.4 mg·g-1 and 281.7 mg·g-1, respectively. The active -Si-O- adsorption sites produced by the breaking of inert Si-O-Si (or M) bonds and the electrostatic interactions of negatively charged adsorbents to adsorbates play a major role in the adsorption process. Adsorption capacities of the developed composite are significantly higher than that of Pal, WPal and hydrothermally treated WPal (HWPal). Results demonstrate that the composite adsorbents have high potential in decontamination of organics in water efficiently.

12.
Adv Mater ; 31(39): e1901964, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31389096

RESUMO

Atomically thin oxychalcogenides have been attracting intensive attention for their fascinating fundamental properties and application prospects. Bi2 O2 Se, a representative of layered oxychalcogenides, has emerged as an air-stable high-mobility 2D semiconductor that holds great promise for next-generation electronics. The preparation and device fabrication of high-quality Bi2 O2 Se crystals down to a few atomic layers remains a great challenge at present. Here, molecular beam epitaxy (MBE) of atomically thin Bi2 O2 Se films down to monolayer on SrTiO3 (001) substrate is achieved by co-evaporating Bi and Se precursors in oxygen atmosphere. The interfacial atomic arrangements of MBE-grown Bi2 O2 Se/SrTiO3 are unambiguously revealed, showing an atomically sharp interface and atom-to-atom alignment. Importantly, the electronic band structures of one-unit-cell (1-UC) thick Bi2 O2 Se films are observed by angle-resolved photoemission spectroscopy (ARPES), showing low effective mass of ≈0.15 m0 and bandgap of ≈0.8 eV. These results may be constructive to the synthesis of other 2D oxychalcogenides and investigation of novel physical properties.

13.
Int J Biol Sci ; 15(7): 1368-1382, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31337968

RESUMO

Recent studies have demonstrated that dermal papilla cell-derived exosomes (DPC-Exos) promote the anagen stage of hair follicle (HF) growth and delay the catagen stage. However, the roles of DPC-Exos in regulating hair follicle stem cell (HFSC) quiescence and activation remain unknown. Here, we found that HFSC differentiation was induced by co-culture with DPCs, and that DPC-Exos attached to the surface of HFSCs. Using micro RNA (miRNA) high-throughput sequencing, we identified 111 miRNAs that were significantly differentially expressed between DPC-Exos and DPCs, and the predicted target genes of the top 34 differentially expressed miRNAs indicated that DPC-Exos regulate HFSCs proliferation and differentiation via genes involved in cellular signal transduction, fatty acid expression regulation, and cellular communication. The overexpression of miR-22-5p indicated that it negatively regulates HFSC proliferation and LEF1 was revealed as the direct target gene of miR-22-5p. We therefore propose the miR-22-5p-LEF1 axis as a novel pathway regulating HFSC proliferation.

14.
Sensors (Basel) ; 19(15)2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31344920

RESUMO

Due to the popularity of smart devices, traditional one-way teaching methods might not deeply attract school students' attention, especially for the junior high school students, elementary school students, or even younger students, which is a critical issue for educators. Therefore, we develop an intelligent interactive education system, which leverages wearable devices (smart watches) to accurately capture hand gestures of school students and respond instantly to teachers so as to increase the interaction and attraction of school students in class. In addition, through multiple physical information of school students from the smart watch, it can find out the crux points of the learning process according to the deep data analysis. In this way, it can provide teachers to make instant adjustments and suggest school students to achieve multi-learning and innovative thinking. The system is mainly composed of three components: (1) smart interactive watch; (2) teacher-side smart application (App); and (3) cloud-based analysis system. Specifically, the smart interactive watch is responsible for detecting the physical information and interaction results of school students, and then giving feedback to the teachers. The teacher-side app will provide real-time learning suggestions to adjust the teaching pace to avoid learning disability. The cloud-based analysis system provides intelligent learning advices, academic performance prediction and anomaly learning detection. Through field trials, our system has been verified that can potentially enhance teaching and learning processes for both educators and school students.

15.
Zool Res ; 40(4): 293-304, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31271004

RESUMO

Divergence of gene expression and alternative splicing is a crucial driving force in the evolution of species; to date, however the molecular mechanism remains unclear. Hybrids of closely related species provide a suitable model to analyze allele-specific expression (ASE) and allele-specific alternative splicing (ASS). Analysis of ASE and ASS can uncover the differences in cis-regulatory elements between closely related species, while eliminating interference of trans-regulatory elements. Here, we provide a detailed characterization of ASE and ASS from 19 and 10 transcriptome datasets across five tissues from reciprocal-cross hybrids of horse×donkey (mule/hinny) and cattle×yak (dzo), respectively. Results showed that 4.8%-8.7% and 10.8%-16.7% of genes exhibited ASE and ASS, respectively. Notably, lncRNAs and pseudogenes were more likely to show ASE than protein-coding genes. In addition, genes showing ASE and ASS in mule/hinny were found to be involved in the regulation of muscle strength, whereas those of dzo were involved in high-altitude adaptation. In conclusion, our study demonstrated that exploration of genes showing ASE and ASS in hybrids of closely related species is feasible for species evolution research.


Assuntos
Alelos , Processamento Alternativo , Bovinos/genética , Equidae/genética , Hibridização Genética/genética , Animais , Sequência de Bases , Regulação da Expressão Gênica , RNA/genética , RNA/metabolismo
16.
FEBS J ; 286(23): 4675-4692, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31276295

RESUMO

The ability to alter single bases without homology directed repair (HDR) of double-strand breaks provides a potential solution for editing livestock genomes for economic traits, which are often multigenic. Progress toward multiplex editing in large animals has been hampered by the costly inefficiencies of HDR via microinjection of in vitro manipulated embryos. Here, we designed sgRNAs to induce nonsense codons (C-to-T transitions) at four target sites in caprine FGF5, which is a crucial regulator of hair length in mammals. Initial transfections of the third generation Base Editor (BE3) plasmid and four different sgRNAs into caprine fibroblasts were ineffective in altering FGF5. In contrast, all five progenies produced from microinjected single-cell embryos had alleles with a targeted nonsense mutation. The effectiveness of BE3 to make single base changes varied considerably based on sgRNA design. In addition, the rate of mosaicism differed between animals, target sites, and tissue type. The phenotypic effects on hair fiber were characterized by hematoxylin and eosin, immunofluorescence staining, and western blotting. Differences in morphology were detectable, even though mosaicism was probably affecting the levels of FGF5 expression. PCR amplicon and whole-genome resequencing analyses for off-target changes caused by BE3 were low at a genome-wide scale. This study provided the first evidence of base editing in large mammals produced from microinjected single-cell embryos. Our results support further optimization of BEs for introgressing complex human disease alleles into large animal models, to evaluate potential genetic improvement of complex health and production traits in a single generation.

17.
PeerJ ; 7: e7230, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31309000

RESUMO

Background: Hair follicles in cashmere goats are divided into primary and secondary hair follicles (HFs). HF development, which determines the morphological structure, is regulated by a large number of vital genes; however, the key functional genes and their interaction networks are still unclear. Although the vitamin D receptor (VDR) is related to cashmere goat HF formation, its precise effects are largely unknown. In the present study, we verified the functions of key genes identified in previous studies using hair dermal papilla (DP) cells as an experimental model. Furthermore, we used CRISPR/Cas9 technology to modify the VDR in DP cells to dissect the molecular mechanism underlying HF formation in cashmere goats. Results: The VDR expression levels in nine tissues of Shaanbei white cashmere goats differed significantly between embryonic day 60 (E60) and embryonic day 120 (E120). At E120, VDR expression was highest in the skin. At the newborn and E120 stages, the VDR protein was highly expressed in the root sheath and hair ball region of Shaanbei cashmere goats. We cloned the complete CDS of VDR in the Shaanbei white cashmere goat and constructed a VDR-deficient DP cell model by CRISPR/Cas9. Heterozygous and homozygous mutant DP cells were produced. The growth rate of mutant DP cells was significantly lower than that of wild-type DP cells (P < 0.05) and VDR mRNA levels in DP cells decreased significantly after VDR knockdown (P < 0.05). Further, the expression levels of VGF, Noggin, Lef1, and ß-catenin were significantly downregulated (P < 0.05). Conclusions: Our results indicated that VDR has a vital role in DP cells, and that its effects are mediated by Wnt and BMP4 signaling.

18.
Nat Commun ; 10(1): 3457, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31358759

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

19.
ChemMedChem ; 14(16): 1484-1492, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31162826

RESUMO

Metal dyshomeostasis is central to a number of disorders that result from, inter alia, oxidative stress, protein misfolding, and cholesterol dyshomeostasis. In this respect, metal deficiencies are usually readily corrected by treatment with supplements, whereas metal overload can be overcome by the use of metal-selective chelation therapy. Deferasirox, 4-[(3Z,5E)-3,5-bis(6-oxo-1-cyclohexa-2,4-dienylidene)-1,2,4-triazolidin-1-yl]benzoic acid, Exjade, or ICL670, is used clinically to treat hemosiderosis (iron overload), which often results from multiple blood transfusions. Cyclodextrins are cyclic glucose units that are extensively used in the pharmaceutical industry as formulating agents as well as for encapsulating hydrophobic molecules such as in the treatment of Niemann-Pick type C or for hypervitaminosis. We conjugated deferasirox, via an amide coupling reaction, to both 6A -amino-6A -deoxy-ß-cyclodextrin and 3A -amino-3A -deoxy-2A (S),3A (S)-ß-cyclodextrin, at the upper and lower rim, respectively, creating hybrid molecules with dual properties, capable of both metal chelation and cholesterol encapsulation. Our findings emphasize the importance of the conjugation of ß-cyclodextrin with deferasirox to significantly improve the biological properties and to decrease the cytotoxicity of this drug.

20.
Insect Biochem Mol Biol ; 111: 103175, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31150761

RESUMO

The silkworm Bombyx mori is a well-characterized model organism for studying the silk gland development and silk production process. Using positional cloning and gene sequencing, we have previously reported that a truncated fibroin heavy chain was responsible for silkworm naked pupa (Nd) mutant. However, the mechanisms by which the mutant FibH causes developmental defects and secretion-deficiency of the silk gland remain to be fully elucidated. Here, silk gland's developmental features, histomorphology, and transcriptome analyses were used to characterize changes in its structure and gene expression patterns between Nd mutant and WT/Dazao. Whole larval stage investigation showed that Nd-PSG undergoes an arrested/delayed development, which eventually resulted in a gland degeneration. By using section staining and transmission electron microscope, a blockade in intracellular vesicle transport from endoplasmic reticulum to Golgi apparatus (secretion-deficiency) and an increased number of autophagosomes and lysosomes were found in Nd-PSG's cytoplasm. Next, by using RNA sequencing and comparative transcriptomic analysis, 2178 differentially expressed genes were identified between Nd-PSG and WT-PSG, among which most of the DEGs associated with cellular stress responses (autophagy, ubiquitin-proteasome system, and heat shock response) were significantly up-regulated in Nd-PSG, suggesting that mutant FibH perturbed cellular homeostasis and resulted in an activation of adaptive responses in PSG cells. These findings reveal the molecular mechanism of the Naked pupa (Nd) mutation and provide insights into silk gland development as well as silk protein production in silkworm Bombyx mori.


Assuntos
Bombyx/crescimento & desenvolvimento , Bombyx/genética , Seda/metabolismo , Transcriptoma , Animais , Bombyx/metabolismo , Glândulas Exócrinas/citologia , Glândulas Exócrinas/crescimento & desenvolvimento , Fibroínas/biossíntese , Fibroínas/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Larva/citologia , Larva/crescimento & desenvolvimento , Mutação , Análise de Sequência de RNA , Seda/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA