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1.
Transfus Clin Biol ; 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33221503

RESUMO

Myelodysplastic syndrome (MDS) is a group of heterogeneous diseases derived from hematopoietic stem cells characterized by hemolytic anemia and high risk of conversion to acute leukemia [1]. MDS is an age-related disease in which approximately 80% of patients are over 60 years of age, male and female. Anemia is the most common clinical condition, and many patients are also associated with infection and bleeding. When the amount of α globin synthesis is insufficient, the remaining ß chain forms tetramer ß4, i.e. HbH. The latter forms a precipitate in red blood cells, leading to hemolytic anemia, called HbH disease, the majority of which is congenital [2], a small number of patients with myelodysplastic syndrome and acute myeloid leukemia may appear HbH (called acquired HbH disease). We reported a 71 years old male patient diagnosed as myelodysplastic syndromes (MDS) in our hospital. The patient has a negative α-thalassemia gene test. The H band is detected by hemoglobin electrophoresis. This article analyzed and discussed this case with MDS, as well reviewed MDS.

2.
BMC Med Genomics ; 13(1): 145, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023625

RESUMO

BACKGROUND: Identification of master regulators (MRs) using transcriptome data in cervical cancer (CC) could help us to develop biomarkers and find novel drug targets to fight this disease. METHODS: We performed differential expression (DE) analyses of public microarray and RNA-seq transcriptome data of CC and normal cervical tissues (N). Virtual Inference of Protein activity by Enriched Regulon analysis (VIPER) was used to convert the DE outcomes to differential activity (DA) signature for MRs. Synergy analysis was conducted to study synergistic effect of MR-pairs. TCGA and microarray data were used to test the association of expression of a MR and a clinical feature or a molecular feature (e.g. somatic mutations). Various bioinformatic tools/websites (DAVID, GEPIA2, Oncomine, cBioPortal) were used to analyze the expression of the top MRs and their regulons. RESULTS: Ten DE and 10 DA signatures were generated for CC. Two MRs, DNA topoisomerase II alpha (TOP2A) and centromere protein F (CENPF) were found to be up-regulated, activated and synergistic in CC compared to N across the 10 datasets. The two MRs activate a common set of genes (regulons) with functions in cell cycle, chromosome, DNA damage etc. Higher expression of CENPF was associated with metastasis. High expression of both MRs is associated with somatic mutation of a set of genes including tumor suppressors (TP53, MSH2, RB1) and genes involved in cancer pathways, cell cycle, DNA damage and repair. The magnitude of up-regulation and the absolute expression level of both MRs in CC are significantly higher compared to many other cancer types. CONCLUSION: TOP2A and CENPF are a synergistic pair of MRs that are overexpressed and activated in CC. Their high expression is correlated with some prognosis features (e.g. metastasis) and molecular features (e.g. somatic mutations) and distinctly high in CC vs. many other cancer types. They may be good biomarkers and anticancer drug targets for CC.

3.
Int J Syst Evol Microbiol ; 70(11): 5861-5867, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33044149

RESUMO

A novel, Gram-stain-positive, aerobic, non-spore-forming, non-motile and irregular rod-shaped bacterium designated Q22T was isolated from the rhizosphere soil of mangrove plant, Kandelia candel collected in Zhangzhou, Fujian province, China. Strain Q22T was able to grow at 10-40 °C (optimum 30 °C), pH 5.5-9.0 (optimum 7.0-8.0) and with 0-5.0% (w/v) NaCl (optimum 1.0 %). The genomic DNA G+C content was 71.9%. The average nucleotide identity, and in silico DNA-DNA hybridization values between strain Q22T and the reference strains were 79.7-88.9% and 22.6-37.4%, respectively. The predominant isoprenoid quinone was MK-12 and the major fatty acids were anteiso-C15:0, iso-C16:0 and anteiso-C17:0. The major polar lipids of strain Q22T were diphosphatidylglycerol, phosphatidylglycerol, one glycolipid and three unidentified lipids. The strain Q22T contained 2,4-diaminobutyric acid, alanine acid, glutamic acid and glycine in the peptidoglycans. The phylogenetic analysis and genotypic features, along with the phenotypic and chemotaxonomic characteristics, indicate that strain Q22T represents a novel species of the genus Agromyces, for which the name Agromyces kandeliae sp. nov. is proposed. The type strain is Q22T (=MCCC 1K03340T= KCTC 39961T).

4.
Exp Ther Med ; 20(5): 24, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32934689

RESUMO

As intraocular pressure (IOP) is primarily higher in the morning, an evening dose of prostaglandin analogs is typically used as monotherapy to decrease IOP in patients with open-angle glaucoma. Travoprost (TV) has reported efficacy in treating open-angle glaucoma; however, the safety and efficacy may be different compared with that for latanoprost (LT). The aim of the present study was to compare the effectiveness and safety of an evening dose of TV compared with that of LT in treating open-angle glaucoma. Data including IOP, results of lid and slit-lamp examination and ophthalmoscopy, as well as adverse effects in 250 affected eyes from patients with open-angle glaucoma who received either TV (n=89) or LT (n=161) once in the evening for 3-months were included in the analyses. At the end of treatment, TV (23.45±1.52 vs. 19.15±1.01 mmHg; P<0.0001) and LT (23.93±2.11 vs. 19.45±1.11 mmHg; P<0.0001) successfully lowered the IOP. In addition, there was no significant difference in the reduction of IOP values at the end of treatment between the two groups (P=0.120). Furthermore, there were no adverse effects on visual acuity (P>0.05), except for non-visual acuity, for example hyperemia (P<0.0001 for both groups), while there was a significant increase in the number of patients with dry eyes receiving TV (P=0.020) and a significant increase with eyelid swelling (P=0.036) and headache (P=0.037) in patients receiving LT. In conclusion, evening doses of TV and LT had the same efficacy and manageable adverse effects in the treatment of open-angle glaucoma (level of evidence, 3).

5.
Anal Chem ; 92(19): 13532-13538, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32900180

RESUMO

Fluorescence methods are important tools to identify RNA-binding small molecules and further employed to study RNA-protein interactions. Most reported fluorescence strategies are based on covalent labeling of ligand or RNA, which can impede the binding between them to some extent, or light-off fluorescent indicator displacement methods, which ask for particular indicators. Herein, a label-free fluorescence strategy based on the light-on aggregation-induced emission (AIE) feature of tetraphenylethene (TPE) derivative to screen RNA-binding small molecules is presented. As a result of electrostatic interaction, the selected peptides can induce self-assembly of the TPE derivative to produce strong fluorescent emission; when the peptides are bound to RNA molecules, the TPE derivative is in the deaggregated form and shows no or minimum fluorescence. Based on the phenomenon, a competitive displacement assay combined with the TPE reporter was employed to characterize selected small molecules for their binding abilities to HIV-I RNAs. This AIE feature enables the fluorescence-off state of the TPE derivative in the presence of RNA-peptide complex to be "lightened up" quickly as the RNA-binding molecule is introduced and the peptide is competitively released. This strategy was carried out to test several small molecule binders, and the results are consistent with previous reports. This report gives an inspiring example of AIE-based fluorescent assay for HIV-I RNA-binding molecule screening, which may further be explored to build a drug screening platform for RNA-protein interference.

6.
J Int Med Res ; 48(8): 300060520934633, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32776862

RESUMO

OBJECTIVE: This study aimed to investigate application of the urine albumin-to-creatinine ratio (ACR), serum beta 2-microglobulin (ß2-MG), and cystatin C as risk markers in a cohort of women with polycystic ovary syndrome (PCOS) for the incidence of gestational diabetes mellitus (GDM). METHODS: In this cross-sectional study, we analyzed 312 pregnant women with PCOS and classified them as those with and without GDM. For all participants, elbow venous blood and clean middle urine were collected in the morning after 8 hours of an empty stomach. RESULTS: Logistic regression analysis showed that the ACR, urine ß2-MG levels, and serum cystatin C levels were important markers for women with PCOS concomitant with GDM. Receiver operating characteristic curve analysis showed that the area under the curve of CysC was 0.81 with the threshold based on >0.93 and that of ß2-MG was 0.72 with the threshold based on >1.25. CONCLUSIONS: Increased levels of ß2-MG and cystatin C and a high ACR might be risk factors for Chinese women with PCOS and GDM during mid-pregnancy.

7.
J Asian Nat Prod Res ; : 1-7, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32851866

RESUMO

Two new milbemycin metabolites, 13α-hydroxymilbemycin ß 13 (1) and 26-methyl-13α-hydroxymilbemycin ß 13 (2), were isolated from the fermentation broth of a genetically engineered strain Streptomyces avermitilis AVE-H39. Their structures were determined by the comprehensive spectroscopic data, including 1 D, 2 D NMR, MS spectral analysis and the comparison with data from the literature. Compounds 1 and 2 not only exhibited potent acaricidal activities against Tetranychus cinnabarinus, but also had nematocidal activity against Bursaphelenchus xylophilus.

8.
Endocrine ; 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32803677

RESUMO

BACKGROUND: Mutations in DUOX2 are the frequent cause of congenital hypothyroidism (CH), a common neonatal metabolic disorder characterized by great phenotypic variability. CH can be traditionally subclassified into two subtypes: thyroid dysgenesis (TD) and thyroid dyshormonogenesis. The objectives of this study were to analyze the genetic data of two familial CH cases, to elucidate the pathogenesis from the perspective of genetics and to review and summarize the previous findings. METHODS: Targeted regions sequencing (TRS) technology covering all exons and intron-exon boundaries of 35 known and potential CH-related candidate target genes in combination with Sanger sequencing were performed to identify the likely pathogenic mutations of the six patients with familial CH. RESULTS: In family 1, two DUOX2 missense mutations, namely, c.1060C>T/p.R354W in exon 10 and c.3200C>T/p.S1067L in exon 25, were found. Patient 1 (P1), P2 and P3 were transient CH (TCH) patients with eutopic thyroid glands of normal size and function. In family 2, only the mutation c.3200C>T/p.S1067L was identified. P4, P5, and P6 were diagnosed with permanent CH (PCH), which requires lifelong levothyroxine (L-T4) treatment. Furthermore, both P4 and P5 harbored properly located thyroid glands, whereas P6 had a mildly reduced gland. P1, P3, P6, and other family members carrying monoallelic or biallelic DUOX2 mutations showed no obvious abnormal clinical symptoms or signs, while P2, P4, and P5 showed umbilical hernias. CONCLUSIONS: The present study suggests that the phenotypic features resulting from DUOX2 mutations vary greatly. The p.R354W and p.S1067L alterations or the combination of the two alterations in DUOX2 are probably only predisposing to CH and DUOX2 may be involved in the morphogenesis of the human thyroid gland. Simultaneously, the compensation of DUOX1 for the loss of DUOX2, undetectable pathogenic mutations, the effects of environmental factors, epigenetic mechanisms and the involvement of multiple genes cannot be excluded in the explanation of these genetic results.

9.
Ecotoxicol Environ Saf ; 203: 110988, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32678761

RESUMO

The screening and identification of hyperaccumulators is the key to the phytoremediation of soils contaminated by heavy metal (HM). Arbuscular mycorrhizal fungus (AMF) can improve plant growth and tolerance to HM; therefore, AMF-assisted phytoextraction has been regarded as a potential technique for the remediation of HM-polluted soils. A greenhouse pot experiment was conducted to determine whether Sphagneticola calendulacea is a Cd-hyperaccumulator and to investigate the effect of the AMF-Funneliformis mosseae (FM) on plant growth and on the accumulation, subcellular distribution and chemical form of Cd in S. calendulacea grown in soils supplemented with different Cd levels. At 25, 50 and 100 mg Cd kg-1 level, S. calendulacea showed high Cd tolerance, the translocation factor and the bioconcentration factor exceeded 1, and accumulation of more than 100 mg Cd kg-1 was observed in the aboveground parts of the plant, meeting the requirements for a Cd-hyperaccumulator. Moreover, FM colonization significantly increased both biomasses and Cd concentration in S. calendulacea. After FM inoculation, the Cd concentrations and proportions increased in the cell walls, but exhibited no significant change in the organelles of the shoots. Meanwhile, FM symbiosis contributed to the conversion of Cd from highly toxic chemical forms (extracted by 80% ethanol and deionized water) to less toxic chemical forms (extracted by 1 M NaCl, 2% acetic acid, 0.6 M HCl) of Cd in the shoots. Overall, S. calendulacea is a typical Cd-hyperaccumulator, and FM symbiosis relieved the phytotoxicity of Cd and promoted plant growth and Cd accumulation, and thus greatly increasing the efficiency of phytoextraction for Cd-polluted soil. Our study provides a theoretical basis and application guidance for the remediation of Cd-contaminated soil by the symbiont of S. calendulacea with FM.


Assuntos
Asteraceae/metabolismo , Bioacumulação , Cádmio/metabolismo , Glomeromycota/fisiologia , Micorrizas/fisiologia , Poluentes do Solo/metabolismo , Asteraceae/crescimento & desenvolvimento , Asteraceae/microbiologia , Biodegradação Ambiental
10.
J Asian Nat Prod Res ; : 1-6, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32608247

RESUMO

Two new milbemycin derivatives, milbemycin M (1) and milbemycin N (2), were isolated from the culture of a genetically engineered strain Streptomyces bingchenggensis BCJ60. Their structures were elucidated through the interpretation of NMR and HR-ESI-MS spectroscopic data, as well as comparison with previous reports. The acaricidal and nematicidal activities of them against Tetranychus cinnabarinus and Bursaphelenchus xylophilus were tested. The results showed that compounds 1-2 possessed potent acaricidal and nematocidal activities.

11.
Nat Prod Res ; : 1-6, 2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32586138

RESUMO

Two new threonine-containing metabolites, N-[4-hydroxy-3-prenyl-benzoyl]-L-threonine (1) and N-[2,2-dimethyl-2H-chromene-6-carbonyl]-L-threonine (2), were isolated from the fermentation broth of the soil fungus Curvularia inaequalis strain HS-FG-257. Their structures were elucidated through the interpretation of HR-ESIMS and extensive NMR spectroscopic data. Both compounds exhibited no cytotoxic activity against the test cell lines A549 and HCT-116.

12.
J Antibiot (Tokyo) ; 73(9): 642-645, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32472052

RESUMO

Two novel milbemycin derivatives, 5,27-epoxy-13α-hydroxy milbemycin ß11 (1) and 5,27-epoxy-13α-hydroxy-25-ethyl milbemycin ß11 (2), were isolated from the genetically engineered strain Streptomyces avermitilis AVE-H39. Their structures were elucidated through the interpretation of HR-ESIMS and extensive NMR spectroscopic data. Compounds 1 and 2 exhibited moderate acaricidal and nematicidal activities.

13.
Front Cell Dev Biol ; 8: 221, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32318571

RESUMO

Mitochondria are highly dynamic organelles, which can form a network in cells through fusion, fission, and tubulation. Its morphology is closely related to the function of mitochondria. The damaged mitochondria can be removed by mitophagy. However, the relationship between mitochondrial morphology and non-selective autophagy is not fully understood. We found that mitochondrial fusion machinery, not fission or tubulation machinery, is essential for energy deprivation-induced autophagy. In response to glucose starvation, deletion of mitochondrial fusion proteins severely impaired the association of Atg1/ULK1 with Atg13, and then affected the recruitment of Atg1 and other autophagic proteins to PAS (phagophore assembly site). Furthermore, the deletion of fusion proteins blocks mitochondrial respiration, the binding of Snf1-Mec1, the phosphorylation of Mec1 by Snf1, and the dissociation of Mec1 from mitochondria under prolonged starvation. We propose that mitochondrial fusion machinery regulates energy deprivation-induced autophagy through maintaining mitochondrial respiration.

14.
Medicine (Baltimore) ; 99(16): e19607, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32311929

RESUMO

Studies of maternal oral contraceptive pill (OCP) exposure and the offspring's risk of atopic diseases are of current interest due to concerns about widespread use of OCP before or during pregnancy.We evaluated whether maternal OCP exposure is associated with an increased risk of atopic diseases by reviewing the literature and performing a meta-analysis. The PubMed and Embase databases were searched to identify potential studies for inclusion. Three common atopic outcomes were included: asthma, eczema, and rhinitis.We found 693 titles, abstracts, and citations, and 6 studies were included in this analysis. A meta-analysis revealed that maternal OCP exposure was associated with higher odds of asthma (odds ratio [OR] 1.1; 95% confidence interval [CI] 1.02-1.19; P = .014), rhinitis (OR 1.34; 95% CI 1.07-1.68; P = .011) during childhood, whereas there was no association with eczema (OR 1.17; 95% CI 0.81-1.68; P = .383). This analysis was limited by the small number of studies included and the limited adjustments for the possible confounders in the studies.Current evidence suggests that maternal OCP exposure increases the risk for respiratory allergic diseases (asthma and rhinitis) in the offspring, but not for eczema. Given the few studies included, future larger, prospective studies that control for important confounders are needed to verify our findings.


Assuntos
Asma/epidemiologia , Anticoncepcionais Orais , Dermatite Atópica/epidemiologia , Exposição Materna/estatística & dados numéricos , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Rinite Alérgica/epidemiologia , Criança , Feminino , Humanos , Razão de Chances , Gravidez , Fatores de Risco
15.
Sci Rep ; 10(1): 1849, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32001722

RESUMO

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

16.
Org Lett ; 22(3): 1113-1116, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-31977234

RESUMO

Novel antilipid peroxidative carbazole alkaloids, antiostatin A5 (1), antiostatin A6 (2), and (±)-morindolestatin (3), were isolated from a new soil-derived Streptomyces sp. Compound 2 possesses an unusual cyclohexene side chain. Compound 3 was a pair of enantiomers featuring an unprecedented [1,4]oxazino[2,3-c]carbazole ring system. The absolute configuration of 3 was determined by online HPLC-ECD and ECD calculation. A racemization mechanism and putative biosynthetic pathway are discussed.

17.
Cell Host Microbe ; 27(1): 115-128.e8, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31917956

RESUMO

Antiviral immunity in insects is mediated by the RNA interference (RNAi) pathway. Viruses evade antiviral RNAi by expressing virulence factors known as viral suppressors of RNAi (VSR). Here, we report the identification of VINR, a Drosophila VSR-interacting long non-coding (lnc) RNA that activates non-canonical innate immune signaling upon detection of the dsRNA-binding VSR of Drosophila C virus (DCV). VINR is required for the induction of antimicrobial peptide (AMP) genes but dispensable for antiviral RNAi. VINR functions by preventing the ubiquitin proteasome-dependent degradation of Cactin, a coiled-coil and arginine-serine-rich domain-containing protein that regulates a non-cannonical antimicrobial pathway for AMP induction. CRISPR-Cas9 knockout of VINR in Drosophila cells enhances DCV replication independently of antiviral RNAi, and VINR-knockout adult flies exhibit enhanced disease susceptibility to DCV and bacteria. Our findings reveal a counter counter-defense strategy activated by a lncRNA in response to the viral suppression of the primary antiviral RNAi immunity.


Assuntos
Proteínas de Transporte/metabolismo , Dicistroviridae/imunologia , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/imunologia , RNA Longo não Codificante , Animais , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/metabolismo , Sistemas CRISPR-Cas , Dicistroviridae/genética , Dicistroviridae/patogenicidade , Drosophila melanogaster/genética , Técnicas de Silenciamento de Genes , Imunidade Inata , Interferência de RNA/imunologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/imunologia , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Proteínas Virais/metabolismo , Fatores de Virulência/metabolismo
18.
Angew Chem Int Ed Engl ; 59(2): 663-668, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31650689

RESUMO

Expanding the number of nucleotides in DNA increases the information density of functional DNA molecules, creating nanoassemblies that cannot be invaded by natural DNA/RNA in complex biological systems. Here, we show how six-letter GACTZP DNA contributes this property in two parts of a nanoassembly: 1) in an aptamer evolved from a six-letter DNA library to selectively bind liver cancer cells; and 2) in a six-letter self-assembling GACTZP nanotrain that carries the drug doxorubicin. The aptamer-nanotrain assembly, charged with doxorubicin, selectively kills liver cancer cells in culture, as the selectivity of the aptamer binding directs doxorubicin into the aptamer-targeted cells. The assembly does not kill untransformed cells that the aptamer does not bind. This architecture, built with an expanded genetic alphabet, is reminiscent of antibodies conjugated to drugs, which presumably act by this mechanism as well, but with the antibody replaced by an aptamer.

19.
J Am Chem Soc ; 141(44): 17493-17497, 2019 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-31609609

RESUMO

The affinity of aptamers relies on their adaptive folding, but the excessive flexibility of the aptamer backbone usually hampers the folding process. Thus, there is an urgent need to engineer aptamers with more stable and defined structures. Herein, we report a postselection strategy for stabilizing aptamer structures, by fixing both termini of the aptamer with a length-optimized triple helix structure. An anti-lysozyme aptamer was engineered in this way, and its affinity was enhanced by almost 10-fold. An electrochemical aptasensor was designed based on this engineered aptamer, assisted by a DNA tetrahedron as a spacer to orient the aptamer. The aptasensor achieved a 180-fold lower limit of detection than that achieved by the aptasensor without termini-fixed aptamer and exhibited high sensitivity and selectivity toward lysozyme in real red wine samples. This work sheds light on engineering aptamers to achieve enhanced affinity and on the application of aptasensors in complex matrices.

20.
ACS Appl Mater Interfaces ; 11(45): 42856-42864, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31633324

RESUMO

Poly(acrylic acid) (PAA) hydrogels with a multi-bond network composed of sparse chemical cross-links and carboxyl-Fe3+ coordination are prepared through a controllable permeation strategy utilizing ferric citrate (FeCA). The existing strategies that directly soak PAA hydrogels in Fe3+ solutions usually induce an inhomogeneous network with densely cross-linked shells and uncertain water content of the hydrogels, which brings about ambiguity when investigating strengthening mechanisms because water content significantly affects the mechanical properties of hydrogels. Herein, the controllable permeation of Fe3+ into PAA networks based on the competition between citric acid (CA)-Fe3+ chelation and PAA-Fe3+ coordination guarantees sustained release of Fe3+, facilitating homogeneous distribution of ionic cross-links and a certain water content. The obtained hydrogels exhibit excellent and balanced mechanical properties (high tensile strength of 3.28 to 6.95 MPa with large elongations at break of 1400 to 780% when water content decreases from 80 to 50 wt %). The real robust tensile strength of this hydrogel originates from the effective energy dissipation of the homogeneous PAA-Fe3+ cross-links, and the high water content ensures a large elongation at break. Furthermore, the hydrogel also has pH-responsive and shape-memory properties.

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