Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.966
Filtrar
1.
Gene ; 724: 144144, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31629819

RESUMO

BACKGROUND/AIMS: Rheumatoid arthritis synovial fibroblasts (RASF) play an essential role in the pathogenesis of rheumatoid arthritis (RA). This study aimed to investigate the biological effects of miR-22 on RASFs. METHODS: RT-qPCR was used to detect the expressions of miR-22 and SIRT1 in RA synovial tissue. The results of miR-22 on the proliferation of RASF were examined by MTT assay. The effects of miR-22 on the secretion of TNF-α, IL-1ß, and IL-6 in RASF were measured by ELISA. Target gene prediction and screening, and luciferase reporter assay were used to testify downstream target genes of miR-22. RT-qPCR and western blotting were used to detect the mRNA and protein expression of SIRT1. RESULTS: miR-22 was significantly decreased in RA synovial tissue, while SIRT1 was significantly increased in RA synovial tissue. Over-expression of miR-22 significantly inhibited the proliferation of RASFs and the secretions of inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in RASFs. SIRT1 was identified as a direct target of miR-22. Over-expression of miR-22 reduced the expression level of SIRT1 in RASFs. Over-expression of SIRT1 reversed the effect of miR-22 on the proliferation of RASFs and the secretion of inflammatory cytokines. CONCLUSION: MIR-22 was significantly down-regulated in RASF cells, which affected the secretions of inflammatory cytokines and cell proliferation by regulating SIRT1.

2.
Nanotechnology ; 31(2): 025703, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31550702

RESUMO

We have investigated the response of the high entropy alloy of CoNiCrFeMn to the bombardment under extreme irradiation flux by means of molecular dynamics simulations. Compared to pristine Ni single crystalline, the CoNiCrFeMn HEA had less point defects during a single primary knock-on atom process. The average depth of defects was shallower. For consecutive bombardments, the CoNiCrFeMn HEA demonstrated much higher surface irradiation resistance than pristine Ni. Under the irradiation flux of 5.59 × 1027 n/(m^2*s), the number of defects in Ni gradually increased and was proportional to the number of bombardments, till the formation of dislocation which led to a boost of the defects. On the contrary, the number of defects in CoNiCrFeMn HEA was much less and stable, appearing to be insensitive to the number of bombardments and suggesting good radiation resistance. Such radiation resistance of CoNiCrFeMn HEA was attributed to the lattice distortion and sluggish diffusion of atoms, which could enhance the recombination of defects. Under the irradiation flux of 1.68 × 1028 n/(m^2*s), the boost of the defects in Ni occurred at lower number of bombardments. In addition, under both the irradiation flux of 5.59 × 1027 and 1.68 × 1028 n/(m^2*s), CoNiCrFeMn HEA had a smaller number of point defects and the defects were well dispersed. Our results showed that compared with Ni matrix, CoNiCrFeMn HEA had higher surface bombardment tolerance. This study might be helpful in the design of first-wall materials under the extreme irradiation flux.

3.
Food Microbiol ; 86: 103342, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31703884

RESUMO

As the spirit of Chinese Sichuan cuisine, Pixian Doubanjiang (DBJ) is an indispensable flavor condiment and has been widely used for centuries, which is made from red pepper (Capsicum annuum L.), meju and brine after open ripening fermentation. In this study, the physicochemical factors including pH value, titratable acidity, moisture, organic acids, free amino acids and volatile components etc., were identified; the compositions of microbial communities and representative microbiota were investigated; the correlations between physicochemical factors and representative microbial taxa were analyzed, at different ripening stages. The results indicated that the organic acids were all relatively stable starting from the 12th month; most of the free amino acids (17/20) reached the peak concentrations at the 6th month and 28 volatile components were considered as major odorant flavors in DBJ. Zygosaccharomyces rouxii could be the key microorganism associated with 10 volatile components to the maturing of DBJ flavor. The comprehensive analysis on the physicochemical changes related to the succession of microbiota is expected to help us understand the maturing of the taste and flavor in DBJ production.

4.
JCI Insight ; 4(21)2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31672932

RESUMO

Worldwide, over a billion people suffer from chronic liver diseases, which often lead to fibrosis and then cirrhosis. Treatments for fibrosis remain experimental, in part because no unifying mechanism has been identified that initiates liver fibrosis. Necroptosis has been implicated in multiple liver diseases. Here, we report that O-linked ß-N-acetylglucosamine (O-GlcNAc) modification protects against hepatocyte necroptosis and initiation of liver fibrosis. Decreased O-GlcNAc levels were seen in patients with alcoholic liver cirrhosis and in mice with ethanol-induced liver injury. Liver-specific O-GlcNAc transferase-KO (OGT-LKO) mice exhibited hepatomegaly and ballooning degeneration at an early age and progressed to liver fibrosis and portal inflammation by 10 weeks of age. OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis. Furthermore, glycosylation of RIPK3 by OGT is associated with reduced RIPK3 protein stability. Taken together, these findings identify OGT as a key suppressor of hepatocyte necroptosis, and OGT-LKO mice may serve as an effective spontaneous genetic model of liver fibrosis.

5.
Bioorg Med Chem Lett ; : 126638, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31685340

RESUMO

Viral infectivity factor (Vif) is one of the accessory protein of human immunodeficiency virus type I (HIV-1) that inhibits host defense factor, APOBEC3G (A3G), mediated viral cDNA hypermutations. Previous work developed a novel Vif inhibitor 2-amino-N-(2-methoxyphenyl)-6-((4-nitrophenyl)thio)benzamide (1) with strong antiviral activity. Through optimizations on the two side branches, a series of compound 1 derivatives (2-18) were designed, synthesized and tested in vitro for their antiviral activities. The biological results showed that compound 5 and 16 inhibited the virus replication efficiently with EC50 values of 9.81 and 4.62 µM. Meanwhile, low cytotoxicities on H9 cells were observed for the generated compounds by the MTT assay. The structure-activity relationship of compound 1 was preliminarily clarified, which gave rise to the development of more potent Vif inhibitors.

6.
Eur J Pharmacol ; : 172775, 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31689413

RESUMO

Individuals with traumatic brain injury (TBI) manifest a high incidence of depression, which is associated with an impaired recovery from TBI and a lower quality of life. Several neurobiological changes in patients with TBI contribute a form of depression that is unique to that of general depression. This is evinced by the poor efficacy of antidepressants in treating post-TBI depression relative to general depression. In general, however, the treatment of post-TBI depression has received relatively scattered attention in the literature. The purpose of this review is thus to discuss about the possible pathology of depression following TBI and summarize the recent findings on the treatment of it in clinical studies. While both pharmacological and non-pharmacological approaches can reportedly attenuate depressive symptoms in patients with TBI to a moderate extent, the various limitations of such studies require that further well-powered, randomized controlled trials with larger sample sizes and longer follow-ups are warranted to investigate the exact pathophysiology underlying post-TBI depression, the mechanism underlying treatment efficacy, and the optimal pharmacological and non-pharmacological interventions for this population. A combination of different treatments in a comprehensive therapeutic regimen may be an optimal direction for future research.

7.
Crit Rev Microbiol ; : 1-18, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31691607

RESUMO

Metagenomic next-generation sequencing (mNGS) is increasingly being applied in clinical laboratories for unbiased culture-independent diagnosis. Whether it can be a next routine pathogen identification tool has become a topic of concern. We review the current implementation of this new technology for infectious disease diagnostics and discuss the feasibility of transforming mNGS into a routine diagnostic test. Since 2008, numerous studies from over 20 countries have revealed the practicality of mNGS in the work-up of undiagnosed infectious diseases. mNGS performs well in identifying rare, novel, difficult-to-detect and coinfected pathogens directly from clinical samples and presents great potential in resistance prediction by sequencing the antibiotic resistance genes, providing new diagnostic evidence that can be used to guide treatment options and improve antibiotic stewardship. Many physicians recognized mNGS as a last resort method to address clinical infection problems. Although several hurdles, such as workflow validation, quality control, method standardisation, and data interpretation, remain before mNGS can be implemented routinely in clinical laboratories, they are temporary and can be overcome by rapidly evolving technologies. With more validated workflows, lower cost and turnaround time, and simplified interpretation criteria, mNGS will be widely accepted in clinical practice. Overall, mNGS is transforming the landscape of clinical microbiology laboratories, and to ensure that it is properly utilised in clinical diagnosis, both physicians and microbiologists should have a thorough understanding of the power and limitations of this method.

8.
J Cell Biochem ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31692098

RESUMO

Hepatic fibrosis is a chronic inflammatory and reversible repair reaction of the liver under the continuous action of virus or various injuries. In this study, we aimed at identifying the role of miR-326 in the hepatic stellate cell (HSC) activation and liver fibrosis and its potential mechanism. In this study, the liver fibrosis mouse model was developed by injecting CCl4 . Liver tissue morphology was observed and the expression level of α-smooth muscle actin, collagen1α1 and miR-326 was measured. Target gene identification was performed by loss-of-function and gain-of-function. The effect of miR-326 on the expression level of the cytokines associated with the TLR4/MyD88/nuclear factor-κB (NF-κB) pathway was assessed in vitro and in vivo. We show that miR-326 was downregulated in CCl4 -induced fibrotic mice and activated HSCs. The target gene of miR-326 is TLR4. Moreover, miR-326 inhibited the activation of HSCs in vitro through TLR4/MyD88/NF-κB signaling. miR-326 attenuated hepatic fibrosis and inflammation of CCl4 -induced mice in vivo. Our results demonstrate for the first time that miR-326 inhibits HSC activation through TLR4/MyD88/NF-κB signaling. Furthermore, miR-326 plays critical roles in attenuating liver fibrosis and inflammation, suggesting the therapeutic potential of miRNAs.

9.
Nature ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666695

RESUMO

Mitochondria are essential regulators of cellular energy and metabolism, and have a crucial role in sustaining the growth and survival of cancer cells. A central function of mitochondria is the synthesis of ATP by oxidative phosphorylation, known as mitochondrial bioenergetics. Mitochondria maintain oxidative phosphorylation by creating a membrane potential gradient that is generated by the electron transport chain to drive the synthesis of ATP1. Mitochondria are essential for tumour initiation and maintaining tumour cell growth in cell culture and xenografts2,3. However, our understanding of oxidative mitochondrial metabolism in cancer is limited because most studies have been performed in vitro in cell culture models. This highlights a need for in vivo studies to better understand how oxidative metabolism supports tumour growth. Here we measure mitochondrial membrane potential in non-small-cell lung cancer in vivo using a voltage-sensitive, positron emission tomography (PET) radiotracer known as 4-[18F]fluorobenzyl-triphenylphosphonium (18F-BnTP)4. By using PET imaging of 18F-BnTP, we profile mitochondrial membrane potential in autochthonous mouse models of lung cancer, and find distinct functional mitochondrial heterogeneity within subtypes of lung tumours. The use of 18F-BnTP PET imaging enabled us to functionally profile mitochondrial membrane potential in live tumours.

10.
Int J Biol Macromol ; 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31669469

RESUMO

Cofactor regeneration is an important method to avoid the consumption of large quantities of oxidized cofactor NAD+ in enzyme-catalyzed reactions. Herein, glycerol dehydrogenase (GDH) and NADH oxidase preparations by aggregating enzymes with ammonium sulphate followed by cross-linking formed aggregates for effective regeneration of NAD+. After optimization, the activity of combi-CLEAs and separate CLEAs mixtures were 950 and 580 U/g, respectively. And the catalytic stability of combi-CLEAs against pH and temperature was superior to the free enzyme mixture. After ten cycles of reuse, the catalytic efficiency could still retain 63.3% of its initial activity, indicating that the constructed combi-CLEAs system had excellent reusability. Also, the conversion of glycerol to 1,3-dihydroxyacetone (DHA) was improved by the constructed NAD+ regeneration system, resulting in 4.6%, which was 2.5 times of the free enzyme system. Thus, wide applications of this co-immobilization method in the production of various chiral chemicals could be expected in the industry for its high efficiency at a low cost.

11.
J Ethnopharmacol ; : 112338, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31669666

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Fritillariae cirrhosae (FC), referred to'Chuan beimu'in China. As an important edible and medicinal plant, the bulbs of F.cirrhosae is used traditionally in the treatment of pulmonary diseases associated with lung heat, inflammation and tumors. In the study, we investigated the effect of aqueous extract of FC (FC-AE) and elucidated its mechanism in non-small cell lung cancer A549 cells and a xenograft model of nude mice. MATERIALS AND METHODS: CCK-8 and plate colony formation assay were used to evaluate the effect of FC-AE in A549 cells in vitro, and the gene expression profile of FC-AE on A549 cells was assessed by RNA sequencing system. Then, the effects of FC-AE on cell cycle and apoptosis of A549 cells were analyzed by flow cytometry. In combination with RNA-seq data, RT-PCR and western blot were used to evaluate the expression of proteins related to apoptosis and immune regulation. A xenograft model of nude mice was used to assess the effect of FC-AE in vivo. RESULTS: CCK-8 and plate cloning assays showed that FC-AE inhibited the proliferation and colony formation of A549 cells. A549 cells treated with FC-AE can triggered apoptosis. GO and KEGG pathway enrichment analysis of RNA-seq data showed that most of the differentially expressed genes (DEGs) were related to immune response, apoptosis and cell cycle process. Several immune and apoptotic DEGs were identified by qRT-PCR which were consistented with RNA-seq data. In nude mice, FC-AE reduced the tumor size and promoted the secretion of cytokines IL12 and IFNγ. FC-AE up-regulated the two members (STAT1 and STAT4) of STATs and their target genes (IFNγ and IL-12, respectively) protein expressions, and actively regulates Bcl-2/Bax family proteins which resulted in cellular apoptosis in A549 cells. CONCLUSION: Our finding suggests that FC-AE mediates apoptosis through a STAT1 and STAT4-mediated co-regulatory network, which may be the key novel mechanism for its antitumor activity. The F. cirrhosa may be a promising antitumor drug for modulating immune responses to improve cancer therapy.

12.
Drug Des Devel Ther ; 13: 3669-3682, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695334

RESUMO

Purpose: The lack of effective therapies mandates the development of new treatment strategies for vascular dementia (VaD). G protein-coupled receptor 124 (GPR124) may be a therapeutic target for angiogenesis-related diseases of CNS, including VaD. The GCPF peptide is a truncated and screened fragment of the GPR124 extracellular domain. The potential use of GCPF for VaD treatment, angiogenesis and targeting of integrin αvß3 are evaluated. Methods and results: First, the in vivo results indicated that the GCPF peptide could decrease mean escape latency and increase platform crossing times in BCCAO rats. Second, the in vitro and ex vivo results indicated that the GCPF peptide was an active angiogenic peptide and could promote hCMEC/D3 cell migration and adhesion to ECM molecules. Third, in silico analyses predicted that GCPF could specifically interact with integrin αvß3; the ∆G of GCPF binding to the binding pocket was -16.402 KJ/mol. The molecular characteristics indicated that highly hydrophilic GCPF with a pI of 11.70 had a short half-life in mammals (~1 hr). Finally, the ELISA experiments indicated that low dissociation constant (Kd= 2.412±0.455 nM) corresponds to the high affinity of GCPF for integrin αvß3. Conclusion: The data indicate that adhesion of GCPF immobilized on ECM surface to endothelial cells via integrin αvß3 modulates cellular functions to promote angiogenesis and improve cognitive function. This is the first report to prove that GCPF, a novel octapeptide, may be an effective strategy for VaD therapy.

13.
Math Biosci Eng ; 16(6): 6975-6989, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31698599

RESUMO

The traditional path optimization problem is to consider the shortest path of the vehicle, but the shortest path does not effectively reduce the logistics cost. On the contrary, in the case of one-sided pursuit of the shortest path, it may cause some negative effects. This paper constructs a more realistic path optimization model on the path of traditional logistics distribution, and designs a path model based on simulated annealing algorithm which taking fuel consumption, cost, road gradient and condition of vehicle into account. The algorithm model of load capacity and other problems is used to verify the algorithm of the model through a simulation case of multiple distribution points. The experimental results show that the path optimization strategy considering the gradient of the road reduces the cost of the vehicle path, indicating the correctness of considering the vehicle load and road gradient factors in logistics transportation.

14.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(11): 1077-1080, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31703129

RESUMO

OBJECTIVE: To assess the value of detecting multiple rearrangements of MLL gene in children with acute mononuclear leukemia (AML). METHODS: Eighty six children with AML were analyzed by fluorescence in situ hybridization (FISH), chromosomal karyotyping and multiplex reverse transcription-PCR (RT-PCR). RESULTS: Cross signals were detected by FISH in 26 cases, and 30.2% were detected with MLL gene rearrangements. R-band karyotyping analysis revealed 14 translocations with breakages involving 11q23 and 5 other aberrations, which yielded an overall detection rate of 22.1%. Multiple RT-PCR has detected 12 fusion genes produced by the MLL translocation, which yielded a detection rate of 14.0%. A significant difference was found in the detection rate of the three methods (P< 0.05). CONCLUSION: Combined use of FISH, chromosomal karyotyping and multiplex RT-PCR can improve the detection of MLL gene rearrangements and provide important clues for clinical diagnosis, treatment and prognosis of AML.

15.
Molecules ; 24(22)2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31703299

RESUMO

Particulate methane monooxygenase (pMMO) is a characteristic membrane-bound metalloenzyme of methane-oxidizing bacteria that can catalyze the bioconversion of methane to methanol. However, in order to achieve pMMO-based continuous methane-to-methanol bioconversion, the problems of reducing power in vitro regeneration and pMMO stability need to be overcome. Methanobactin (Mb) is a small copper-chelating molecule that functions not only as electron carrier for pMMO catalysis and pMMO protector against oxygen radicals, but also as an agent for copper acquisition and uptake. In order to improve the activity and stability of pMMO, methanobactin-Cu (Mb-Cu)-modified gold nanoparticle (AuNP)-pMMO nanobiohybrids were straightforwardly synthesized via in situ reduction of HAuCl4 to AuNPs in a membrane fraction before further association with Mb-Cu. Mb-Cu modification can greatly improve the activity and stability of pMMO in the AuNP-pMMO nanobiohybrids. It is shown that the Mb-Cu-modified AuNP-pMMO nanobiohybrids can persistently catalyze the conversion of methane to methanol with hydroquinone as electron donor. The artificial heterogeneous nanobiohybrids exhibited excellent reusability and reproducibility in three cycles of catalysis, and they provide a model for achieving hydroquinone-driven conversion of methane to methanol.

16.
Food Chem ; : 125726, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31704069

RESUMO

In our present study, we aimed to explore the effects of hot air and UV-C on anthocyanins and the interaction among anthocyanin, sucrose and organic acids in peaches during postharvest storage. Peaches were treated with hot air or UV-C and stored at 1 °C for 35 days. The results showed that both treatments significantly enhanced the accumulation of anthocyanins and suppressed the degradation of sucrose, citric and malic acids. An in vitro test verified that sucrose, citric and malic acid penetrated the tissue and then induced the biosynthesis of anthocyanins by up regulating anthocyanin-related enzymes. In addition, hot air and UV-C directly enhanced the activities and gene expression of related enzymes to promote the accumulation of anthocyanins. PAL, ANS and UFGT played crucial roles in the biosynthesis of anthocyanins in peach fruit after harvest, and these three enzymes can be stimulated by HA, UV-C, sucrose, citric and malic acid.

18.
Life Sci ; : 116882, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31705915

RESUMO

AIMS: Free fatty acids (FFA) is a key contributor to insulin resistance and endothelial dysfunction. However, the precise mechanism underlying the role of FFA remains elusive. This study aimed to investigate the role of NLRP3 (NOD-like receptor pyrin domain containing-3) inflammasome in FFA induced endothelial dysfunction. MAIN METHODS: HUVECs were transfected with NLRP3 siRNA and then stimulated with LPS and palmitate. C57 BL/6J mice transfected with NLRP3 Lenti-Virus were fed with a high-fat diet (HFD). The levels of NLRP3 inflammasome, AMPKα (AMP-activated protein kinase), endothelial nitric oxide synthase (eNOS) and the activity of the insulin signal pathway, in endothelial cells were determined via Western blotting. Endothelial function was determined by measuring the level of endothelium-dependent vasodilatation. KEY FINDINGS: FFA could activate NLRP3 inflammasome and induce IL-1ß release both in vitro. and in vivo. Using siRNA and Lenti-Virus to inhibit NLRP3 abolished palmitate-induced IL-1ß release and restored impaired phosphorylation of IRS-1 (Tyr), Akt (Ser473) and eNOS (Ser1177) and ACh-mediated endothelium-dependent vasorelaxation induced by palmitate. AMPKα activator AICAR(5-aminoimidazole-4-carbox-amide-1-ß-d-ribofuranoside) inhibited NLRP3 inflammasome activation and decreased IL-1ß release and restored impaired insulin signal pathway induced by palmitate. SIGNIFICANCE: NLRP3 inflammasome activation via AMPKα inactivation mediated palmitate-induced endothelial dysfunction through involves IL-1ß-induced insulin signal pathway.

19.
Mar Pollut Bull ; 150: 110670, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31669709

RESUMO

In this study, we investigated the historical variation, source identification, and distribution of heavy metal pollution in sediments of the Pearl River Estuary (PRE) using 210Pb dating. Our results suggest that the heavy metal concentrations were higher in the western part of the estuary. For all heavy metals, Cd was significantly enriched in the sediments. The Pearl River Delta (PRD) has experienced rapid economic development in the past 40 years, a decreasing trend in heavy metal fluxes after 2004 was identified, which suggests a reduction in heavy metal concentrations due to the removal of heavy polluting industries and the effective control of sewage discharge. A binary mixing model reveals that the contributions of anthropogenic Pb ranged from 45.4 to 64%. Based on lead isotopic ratios (206/207Pb and 208/206Pb), it was found that geologic materials and industrial pollution were the main sources of heavy metals in the PRE sediments.

20.
Chem Commun (Camb) ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31697299

RESUMO

The oxygen-containing species in melamine foam carbons are chemically regulated by oxidizing-acid treatment. The optimized carbon anode shows an enhanced potassium-storage performance in terms of reversible capacity, rate performance, and long-term cycling stability. Both structural analysis and theoretical calculations highlight the roles of quinone- and ether-type oxygen species in boosting the potassium-ion storage performance.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA