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1.
J Neuroinflammation ; 18(1): 9, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407614

RESUMO

BACKGROUND: Both genetic factors and environmental hazards, including environmental noise stress, have been associated with gut microbiome that exacerbates Alzheimer's disease (AD) pathology. However, the role and mechanism of environmental risk factors in early-onset AD (EOAD) pathogenesis remain unclear. METHODS: The molecular pathways underlying EOAD pathophysiology following environmental noise exposure were evaluated using C57BL/6 wild-type (WT) and APP/PS1 Tg mouse models. The composition differences in intestinal microbiota were analyzed by 16S rRNA sequencing and Tax4Fun to predict the metagenome content from sequencing results. An assessment of the flora dysbiosis-triggered dyshomeostasis of oxi-inflamm-barrier and the effects of the CNS end of the gut-brain axis was conducted to explore the underlying pathological mechanisms. RESULTS: Both WT and APP/PS1 mice showed a statistically significant relationship between environmental noise and the taxonomic composition of the corresponding gut microbiome. Bacterial-encoded functional categories in noise-exposed WT and APP/PS1 mice included phospholipid and galactose metabolism, oxidative stress, and cell senescence. These alterations corresponded with imbalanced intestinal oxidation and anti-oxidation systems and low-grade systemic inflammation following noise exposure. Mechanistically, axis-series experiments demonstrated that following noise exposure, intestinal and hippocampal tight junction protein levels reduced, whereas serum levels of inflammatory mediator were elevated. Regarding APP/PS1 overexpression, noise-induced abnormalities in the gut-brain axis may contribute to aggravation of neuropathology in the presymptomatic stage of EOAD mice model. CONCLUSION: Our results demonstrate that noise exposure has deleterious effects on the homeostasis of oxi-inflamm-barrier in the microbiome-gut-brain axis. Therefore, at least in a genetic context, chronic noise may aggravate the progression of EOAD.

2.
Bioorg Med Chem Lett ; : 127775, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33412152

RESUMO

Seventeen flavonoids (1-17) were isolated from Sophora alopecuroides L.. Compounds 1 and 2 were new compounds, and compounds 5, 8, 11, 12, and 17 were isolated from S. alopecuroides for the first time. The sources of compounds 1 and 2 were determined from the seeds of S. alopecuroides by UPLC-QE-Orbitrap-MS, and compounds 1, 2, 7, 13, 14, 15, 16, and 17 were proven to improve the insulin resistance of C2C12 myotubes and significantly increase glucose consumption levels. Among them, compounds 1, 2, 13, 14, 16, and 17 could bind to protein tyrosine phosphatase 1B (PTP1B), thereby significantly inhibiting the enzyme activity of PTP1B. Compound 2 had the strongest inhibitory effect, with an inhibition rate of 95.22% at 0.1 µg·mL-1.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33420685

RESUMO

Persisting in opening up and achieving coordinated development of economy, society, and ecology is China's major strategies for achieving sustainable urbanization. Ecological efficiency is a reasonable indicator to measure the development level of a circular economy. Therefore, using the statistical data of 30 provinces in China from 2004 to 2016, this paper uses the super-efficiency SBM model that considers undesired output to measure the eco-efficiency value, which is used to measure the level of circular economy development in each province. Based on this, a panel model is constructed to test the impact of circular economy and FDI on urbanization. The empirical results show that (1) there is a complex nonlinear relationship between the development of circular economy and the advancement of urbanization, and the shape of the curve varies with areas; (2) FDI under environmental regulation is conducive to promoting China's urbanization to achieve green, effective, and sustainable development; and (3) the development of the tertiary industry, human resources, innovation capabilities, and employment situation is conducive to promoting China's urbanization. Finally, based on the empirical results, this paper puts forward policy recommendations to achieve green, efficient, and intelligent development of Chinese cities by promoting the development of a circular economy and strengthening FDI screening.

4.
Phys Chem Chem Phys ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33399593

RESUMO

Deep eutectic solvents (DESs) have been intensively pursued in the field of separation processes, catalytic reactions, polymers, nanomaterial science, and sensing technologies due to their unique features such as the low cost of components, ease of preparation, tunable physicochemical properties, negligible vapor pressure, non-toxicity, renewability, and biodegradability in the recent decade. Considering these appealing merits, DESs are widely used as extraction agents, solvents and/or catalysts in the desulfurization process since 2013. This review is focused on summarizing the physicochemical properties of DESs (i.e., freezing point, density, viscosity, ionic conductivity, acidity, hydrophilicity/hydrophobicity, polarity, surface tension, and diffusion) to some extent, and their significant advances in applications related to desulfurization processes such as extraction desulfurization, extraction-oxidation desulfurization, and biomimetic desulfurization. In particular, we systematically compile very recent works concerning the selective aerobic oxidation desulfurization (AODS) under extremely mild conditions (60 °C and ambient pressure) via a biomimetic approach coupling DESs with polyoxometallates (POMs). In this system, DESs act as multifunctional roles such as extraction agents, solvents, and catalysts, while POMs serve as electron transfer mediators. This strategy is inspirational since biomimetic or bioinspired catalysis is the "Holy Grail" of oxidation catalysis, which overcomes the difficulty of O2 activation via introducing electron transfer mediators into this system. It not only can be used for AODS, but also paves a novel way for oxidation catalysis, such as the selective oxyfunctionalization of hydrocarbon. Eventually, the conclusion, current challenges, and future opportunities are discussed. The aim is to provide necessary guidance for precisely designing tailor-made DESs, and to inspire chemists to use DESs as a powerful platform in the field of catalysis science.

5.
Front Med ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33400146

RESUMO

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is characterized by genetic alterations with high heterogeneity. Precise subtypes with distinct genomic and/or gene expression patterns have been recently revealed using high-throughput sequencing technology. Most of these profiles are associated with recurrent non-overlapping rearrangements or hotspot point mutations that are analogous to the established subtypes, such as DUX4 rearrangements, MEF2D rearrangements, ZNF384/ZNF362 rearrangements, NUTM1 rearrangements, BCL2/MYC and/or BCL6 rearrangements, ETV6-RUNX1-like gene expression, PAX5alt (diverse PAX5 alterations, including rearrangements, intragenic amplifications, or mutations), and hotspot mutations PAX5 (p.Pro80Arg) with biallelic PAX5 alterations, IKZF1 (p.Asn159Tyr), and ZEB2 (p.His1038Arg). These molecular subtypes could be classified by gene expression patterns with RNA-seq technology. Refined molecular classification greatly improved the treatment strategy. Multiagent therapy regimens, including target inhibitors (e.g., imatinib), immunomodulators, monoclonal antibodies, and chimeric antigen receptor T-cell (CAR-T) therapy, are transforming the clinical practice from chemotherapy drugs to personalized medicine in the field of risk-directed disease management. We provide an update on our knowledge of emerging molecular subtypes and therapeutic targets in BCP-ALL.

6.
Dev Comp Immunol ; : 103990, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33422554

RESUMO

Toll-like receptors (TLRs) play an important role in innate immune through recognizes pathogens. In order to reveal the evolutionary patterns and adaptive evolution of avian TLRs, we examined 66 representative bird species in 26 orders. Phylogenetic results indicated that TLR1A and TLR1B may have differentiated functionally. Evolutionary analysis showed that the TLR genes in birds under strong Purification selection (0.165∼0.4265). A total of 126 common positively selected codons were identified in 10 TLR genes of avian, and most sites were located in the extracellular leucine-rich repeat (LRR) functional domains, and both environment and feeding habits were external factors driving the evolution of avian TLR genes. Environmental pressures had a greater effect on TLR1B, TLR2B, TLR3 and TLR4, while feeding habits were active in affecting TLR2A, TLR2B, TLR15 and TLR21. Our data suggested that TLR genes have been subjected to different selective pressures in the diversification of birds and that these changes enabled them to respond differently to pathogens from diverse sources.

7.
Chemistry ; 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33427337

RESUMO

Divergent synthesis of a variety of 2α and 5α substituted furan derivatives from 2-hydroxy-1,4-diones were reported. By using proper substrate and acid catalyst, the reactions can selectively occur via cyclization/1,6-conjugate addition cascade or cyclization/Fridel-Craft type cascade reaction. A broad range of nucleophilic reagents (> 10 types for 1,6-conjugate addition and > 20 types for Fridel-Craft type cascade reaction) including alcohol, amide, furan, thiophene, pyrrole, indole, phenol, and many others, can successfully participate in the reaction, providing a universal strategy for diversity-oriented synthesis of α-substituted furan derivatives. Deuteration experiment and DFT calculations were carried out to support the proposed reaction mechanisms. Antifungal activity experiments reveal that products with indole or 4-hydroxycoumarin core substituted at 2α position show moderate activities against Botrytis cinerea and Rhizoctorzia solani respectively.

8.
Cell Mol Immunol ; 18(1): 171-181, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31900457

RESUMO

Thymic involution during aging is a major cause of decreased T-cell production and reduced immunity. Here, we show that the loss of CD147 on T cells prevents thymic senescence, resulting in slowed shrinkage of the thymus with age and increased production of naive T cells. This phenotype is the result of slowing of the epithelial-mesenchymal transition (EMT) process in thymic epithelial cells (TECs), which eventually leads to reduced adipocyte accumulation. In an in vitro coculture system, we found that TGFß is an important factor in the EMT process in TECs and that it can reduce the expression of E-cadherin through p-Smad2/FoxC2 signaling. Moreover, CD147 on T cells can accelerate the decline in E-cadherin expression by interacting with Annexin A2 on TECs. In the presence of TGFß, Annexin A2 and E-cadherin colocalize on TECs. However, CD147 on T cells competitively binds to Annexin A2 on TECs, leading to the isolation of E-cadherin. Then, the isolated E-cadherin is easily phosphorylated by phosphorylated Src kinase, the phosphorylation of which was induced by TGFß, and finally, p-E-cadherin is degraded. Thus, in the thymus, the interaction between T cells and TECs contributes to thymic involution with age. In this study, we illuminate the mechanism underlying the triggering of the EMT process in TECs and show that inhibiting TGFß and/or CD147 may serve as a strategy to hinder age-related thymic involution.

9.
Insect Sci ; 28(1): 251-260, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32065478

RESUMO

The geomagnetic field (GMF) is well documented for its essential role as a cue used in animal orientation or navigation. Recent evidence indicates that the absence of GMF (mimicked by the near-zero magnetic field, NZMF) can trigger stress-like responses such as reduced body weight, as we have previously shown in the brown planthopper, Nilaparvata lugens. In this study, we found that consistent with the significantly decreased body weight of newly emerged female (-14.67%) and male (-13.17%) adult N. lugens, the duration of the phloem ingestion feeding waveform was significantly reduced by 32.02% in 5th instar nymphs reared under the NZMF versus GMF. Interestingly, 5th instar nymphs that exhibited reduced feeding had significantly higher glucose levels (+16.98% and +20.05%; 24 h and 48 h after molting), which are associated with food aversion, and expression patterns of their appetite-related neuropeptide genes (neuropeptide F, down-regulated overall; short neuropeptide F, down-regulated overall; adipokinetic hormone, up-regulated overall; and adipokinetic hormone receptor, down-regulated overall) were also altered under the absence of GMF in a manner consistent with diminishing appetite. Moreover, the expressions of the potential magnetosensor cryptochromes (Crys) were found significantly altered under the absence of GMF, indicating the likely upstream signaling of the Cry-mediated magnetoreception mechanisms. These findings support the hypothesis that strong changes in GMF intensity can reduce adult body weight through affecting insect feeding behavior and underlying regulatory processes including appetite regulation. Our results highlight that GMF could be necessary for the maintenance of energy homeostasis in insects.

10.
Org Lett ; 23(1): 118-123, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33351637

RESUMO

With the assistance of a practical directing group (COAQ), the first catalytic protocol for the palladium-catalyzed C(sp3)-H monoarylation of methanol has been developed, offering an invaluable synthesis means to establish extensive derivatives of crucial arylmethanol functional fragments. Furthermore, the gram-scale reaction, broad substrate scope, excellent functional group compatibility, and even the practical synthesis of medicines further demonstrate the usefulness of this strategy.

11.
Innate Immun ; 27(1): 99-106, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32873094

RESUMO

Syphilis is an important health problem worldwide; however, few studies have probed the impact of syphilitic infection on T cell turnover. The mechanisms behind the frequency of T cell subset changes and the associations between these subsets during syphilitic infection remain unclear. Herein, we used a cell-staining method and flow cytometry to explore changes in T cell subpopulations and potential contribution of apoptosis and pyroptosis that triggered therein. We investigated caspase-1-mediated pyroptosis and caspase-3-mediated apoptosis of CD4+ and CD8+ T cells, the major effector lymphocytes with pivotal roles in the pathogenesis of infectious diseases. We found that the levels of caspase-1 and caspase-3 increased in both the circulation and intracellularly in CD4+ and CD8+ T cells. Caspase-1 showed a continual increase from early latent stage infection through to phase 2 disease, whereas caspase-3 increased through to phase 1 disease but declined during phase 2. In addition, serum levels and intracellular expression of caspase-1 and caspase-3 were positively correlated. Overall, this study increases our understanding of how syphilitic infection influences CD4+ and CD8+ T-cell turnover, which may help with designing novel and effective strategies to control syphilis infection and prevent its transmission.

12.
Ultrasound Med Biol ; 47(2): 222-229, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33187758

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused a worldwide pandemic and poses a serious public health risk. It has been proven that lung ultrasound can be extremely valuable in the diagnosis and treatment of the disease, which could also minimize the number of exposed healthcare workers and equipment. Because healthcare workers in ultrasound departments are in close contact with patients who might be infected or virus carriers, it is extremely important that they be provided sufficient protection. Extremely aggressive protection should be avoided because it might lead to a lack of protection equipment for the hospital. Guidance on proper protection management should be provided in detail, for example, how to choose personal protective equipment, how to disinfect the environment. To address these problems, on behalf of the Chinese Ultrasound Doctors Association, Chinese PLA Professional Committee of Ultrasound in Medicine, Beijing Institute of Ultrasound in Medicine and Chinese Research Hospital Association Ultrasound Professional Committee, the authors have summarized the recommendations for effective protection according to existing hygienic standards, their experience and available literature. After the recommendations were completed, two online conferences were held on January 31, 2020 and February 7, 2020, at which the recommendations were discussed in detail. A modified version of the work was circulated and finally approved by all authors, and is the present Chinese Expert Consensus on Protection for Ultrasound Healthcare Workers against COVID-19.


Assuntos
/prevenção & controle , Pessoal de Saúde , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Ultrassonografia/métodos , China , Consenso , Desinfecção , Humanos , Exposição Ocupacional/prevenção & controle , Equipamento de Proteção Individual , Quarentena , Triagem
13.
Ultrasound Med Biol ; 47(1): 43-50, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33082054

RESUMO

This study compared quantitative cartilage ultrasound metrics between people with (n = 12) and without (n = 12) arthroscopic cartilage damage after anterior cruciate ligament injury (age, 24.9 ± 3.7 y; sex, 33% female, 67% male; days since injury = 50 ± 52). A transverse suprapatellar ultrasound assessment imaged the femoral cartilage in participants' injured knees before a clinical arthroscopy. A custom program automatically separated a manual cartilage segmentation into standardized medial and lateral femoral regions and calculated mean thickness (i.e., cross-sectional area/length of cartilage-bone interface), mean echo intensity and echo-intensity heterogeneity. An orthopedic surgeon assessed arthroscopic cartilage damage in the medial and lateral femoral condyles using the Outerbridge grading system (cartilage damage = Outerbridge ≥ 1). Separate logistic regressions for medial and lateral femoral cartilage were used to determine the association between each ultrasound metric and arthroscopic cartilage damage. In medial femoral cartilage, for every 1 standard deviation decrease in echo-intensity mean and heterogeneity, there is, respectively, a 91% (adjusted odds ratio, 0.09; 95% confidence interval, 0.01-0.69) and 97% (adjusted odds ratio, 0.03; 95% confidence interval, 0.002-0.50) increase in the odds of having arthroscopic cartilage damage. Lateral cartilage ultrasound metrics are not associated with lateral arthroscopic cartilage damage. This study provides preliminary evidence that femoral cartilage ultrasound echo intensity is a non-invasive measure associated with medial femoral cartilage health after anterior cruciate ligament injury.

14.
Neuron ; 109(1): 42-58.e8, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33125873

RESUMO

A panel of radiochemicals has enabled in vivo positron emission tomography (PET) of tau pathologies in Alzheimer's disease (AD), although sensitive detection of frontotemporal lobar degeneration (FTLD) tau inclusions has been unsuccessful. Here, we generated an imaging probe, PM-PBB3, for capturing diverse tau deposits. In vitro assays demonstrated the reactivity of this compound with tau pathologies in AD and FTLD. We could also utilize PM-PBB3 for optical/PET imaging of a living murine tauopathy model. A subsequent clinical PET study revealed increased binding of 18F-PM-PBB3 in diseased patients, reflecting cortical-dominant AD and subcortical-dominant progressive supranuclear palsy (PSP) tau topologies. Notably, the in vivo reactivity of 18F-PM-PBB3 with FTLD tau inclusion was strongly supported by neuropathological examinations of brains derived from Pick's disease, PSP, and corticobasal degeneration patients who underwent PET scans. Finally, visual inspection of 18F-PM-PBB3-PET images was indicated to facilitate individually based identification of diverse clinical phenotypes of FTLD on a neuropathological basis.

15.
J Mol Endocrinol ; 66(1): 45-57, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33151904

RESUMO

The aberrant histone methylation patterns contribute to the pathogenesis of endometriosis (EM). Mixed lineage leukemia 1 (MLL1), a histone methyltransferase, is crucial for gene expression by catalyzing the trimethylation of histone 3 lysine 4 (H3K4me3) in gene promoter. This study aimed to explore whether MLL1 is involved in EM-related infertility. The expressions of MLL1 and H3K4me3 were analyzed in the eutopic endometria from EM women with infertility (n = 22) and the normal endometria from EM-free women (n = 22). Mouse EM model was established. The MLL1 and H3K4me3 expression patterns in mice endometria of early pregnancy were also investigated. Immortalized human endometrial stromal cells (iESCs) were cultured and underwent in vitro decidualization. The chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) was performed to find the target gene of MLL1 during decidual process. Results showed that both MLL1 and H3K4me3 decreased in the eutopic endometrium from EM patients compared to that in the normal endometrium. During early pregnancy and the decidual process, MLL1 and H3K4me3 were significantly upregulated in stromal cells. ChIP-seq and ChIP-qPCR found that the cytochrome c oxidase subunit 4I 2 (COX4I2) was directly targeted by MLL1. The dominance of COX4I2-containing enzyme induced the expression of hypoxia-inducible factor-2α (HIF-2α), whose expression in the peri-implantation endometrium is essential for embryo implantation. Further results showed that MLL1 was directly regulated by progesterone (P4) - P4 receptors (PRs). Our study proved that MLL1 was involved in EM-related infertility, which may provide a novel approach to treat the nonreceptive endometrium in EM patients.

16.
J Am Heart Assoc ; 10(1): e017044, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33372536

RESUMO

Background Although silent myocardial infarction (SMI) is prognostically important, the risk of sudden cardiac death (SCD) among patients with incident SMI is not well established. Methods and Results We examined 2 community-based cohorts: the ARIC (Atherosclerosis Risk in Communities) study (n=13 725) and the CHS (Cardiovascular Health Study) (n=5207). Incident SMI was defined as electrocardiographic evidence of new myocardial infarction during follow-up visits that was not present at the baseline. The primary study end point was physician-adjudicated SCD. In the ARIC study, 513 SMIs, 441 clinically recognized myocardial infarctions (CMIs), and 527 SCD events occurred during a median follow-up of 25.4 years. The multivariable hazard ratios of SMI and CMI for SCD were 5.20 (95% CI, 3.81-7.10) and 3.80 (95% CI, 2.76-5.23), respectively. In the CHS, 1070 SMIs, 632 CMIs, and 526 SCD events occurred during a median follow-up of 12.1 years. The multivariable hazard ratios of SMI and CMI for SCD were 1.70 (95% CI, 1.32-2.19) and 4.08 (95% CI, 3.29-5.06), respectively. The pooled hazard ratios of SMI and CMI for SCD were 2.65 (2.18-3.23) and 3.99 (3.34-4.77), respectively. The risk of SCD associated with SMI is stronger with White individuals, men, and younger age. The population-attributable fraction of SCD was 11.1% for SMI, and SMI was associated with an absolute risk increase of 8.9 SCDs per 1000 person-years. Addition of SMI significantly improved the predictive power for both SCD and non-SCD. Conclusions Incident SMI is independently associated with an increased risk of SCD in the general population. Additional research should address screening for SMI and the role of standard post-myocardial infarction therapy.

17.
Sci Total Environ ; 757: 143784, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33229083

RESUMO

The ability for remote-sensing sensors and global/regional models to describe aerosol optical properties (AOPs) is critical to reducing the uncertainty in aerosol radiative forcing associated with climate change, and improving model prediction accuracy. In this study, remote-sensing observations and WRF-Chem simulations were used to evaluate AOPs over Eastern China during a severe winter haze event, in terms of aerosol optical depth (AOD), Ångström exponent (AE) and aerosol extinction profiles (AEP). This study also characterizes whether the inclusion of aerosol radiative feedbacks (ARFs) may improve the ability of WRF-Chem to acquire AOPs during haze episodes. Three simulation scenarios were considered: the non-radiation feedback (NRF), aerosol direct effect (ADE), as well as combined ADE and aerosol indirect effect (ADE + AIE). The results indicate that the satellite AOD products could represent the spatiotemporal distribution characteristics of the haze event. The AOD retrieved by the MODIS C6.1 DB algorithm was highly consistent with ground-based observations. A comparison between simulations and observations demonstrated that WRF-Chem, including the ADE or ADE + AIE scheme, may improve AOPs simulation in heavily polluted areas. The most significant improvements occurred in the Sichuan basin (SB) and North China Plain (NCP) (AOD = 50-70%; AE = 10-20%). In particular, the ADE + AIE scheme was the most obvious for AOD improvement, followed by AE. The AEP was also qualitatively analyzed through simulations and observations, and the result showed that the model overestimates aerosol extinction coefficients in NCP. However, the model is still able to represent the entire AEP contour over East China. Similar to AOD and AE, the model can also improve AEP simulation by adding ADE or ADE + AIE scheme, especially in SB. In summary, it is found that the ability of WRF-Chem to simulate the AOPs was significantly enhanced, particularly for regions loading with heavy aerosol during haze events in Eastern China.

18.
Cell Death Differ ; 28(1): 382-400, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32814878

RESUMO

Anthracyclines are a class of conventional and commonly used frontline chemotherapy drugs to treat breast cancer. However, the anthracycline-based regimens can only reduce breast cancer mortality by 20-30%. Furthermore, there is no appropriate biomarker for predicting responses to this kind of chemotherapy currently. Here we report our findings that may fill this gap by showing the AQP1 (Aquaporin1) protein as a potential response predictor in the anthracycline chemotherapy. We showed that breast cancer patients with a high level of AQP1 expression who underwent the anthracycline treatment had a better clinical outcome relative to those with a low level of AQP1 expression. In the exploration of the underlying mechanisms, we found that the AQP1 and glycogen synthase kinase-3ß (GSK3ß) competitively interacted with the 12 armadillo repeats of ß-catenin, followed by the inhibition of the ß-catenin degradation that led to ß-catenin's accumulation in the cytoplasm and nuclear translocation. The nuclear ß-catenin interacted with TopoIIα and enhanced TopoIIα's activity, which resulted in a high sensitivity of breast cancer cells to anthracyclines. We also found, the miR-320a-3p can attenuate the anthracycline's chemosensitivity by inhibiting the AQP1 expression. Taken together, our findings suggest the efficacy of AQP1 as a response predictor in the anthracycline chemotherapy. The application of our study includes, but is not limited to, facilitating screening of the most appropriate breast cancer patients (who have a high AQP1 expression) for better anthracycline chemotherapy and improved prognosis purposes.

19.
J Anim Breed Genet ; 138(1): 122-134, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32378263

RESUMO

Back and thigh skin of chickens showed significant differences in the thickness and the feather follicle density and size, which are important traits for slaughtered chickens' appearance. In the present study, global gene expression profiling was conducted in the back and thigh skin of chickens using Microarray technology. The results showed that 676 genes were differentially expressed between back and thigh skin. The expression of the differentially expressed genes (DEGs), including PPP1R3C, IGF1, PTCHD1, HOXB6, FGF9, CAMK4, SHH, BMP8B, FOXN1 and PTGER2, was validated by real-time quantitative polymerase chain reaction (RT-qPCR), and the results were consistent with microarray results. Functional analysis revealed that the DEGs were significantly involved in cell proliferation, differentiation, apoptosis, adhesion and transport process, and the pathways were significantly mapped into the ECM-receptor interaction, peroxisome, focal adhesion, Hedgehog and PPAR signalling pathways. Protein-protein interaction network analysis suggested that signalling pathways related to feathers morphogenesis and development, such as Wnt, FGF, MAPK, SHH and BMP signalling pathways, occupied important positions in the network. Genes involved in these signalling pathways and adhesion molecules might play a vital role in skin and feather follicle development. Further single nucleotide polymorphism (SNP) association analysis of Wnt3A showed that the AC genotype of SNP g.255361 C>A significantly increased the feather follicle density of thigh skin. Our findings may provide new insights on candidate genes and pathways related to skin and feather follicle formation of chickens.

20.
Bioorg Chem ; 104: 104325, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33254425

RESUMO

Evolides A (1) and B (2) were isolated from the fruits of Evodia rutaecarpa and characterized by various spectroscopic data analyses (NMR, HRESIMS, ECD, and X-ray crystallography) and were thought to be new unusual terpenoids possessing lactone groups. An in vitro bioassay showed that compound 1 exhibited a significant activation effect on the farnesoid X receptor (EC50 0.73 µM).

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