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1.
Polymers (Basel) ; 12(3)2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32143489

RESUMO

To develop a wound dressing material that conforms to the healing process, we prepared a multilayer composite (MC) membrane consisting of an antibacterial layer (ABL), a reinforcement layer (RFL), and a healing promotion layer (HPL). Biocompatible zein/ethyl cellulose (zein/EC) electrospun nanofibrous membranes with in situ loaded antibacterial photosensitizer protoporphyrin (PPIX) and healing promotion material vaccarin (Vac) were, respectively, chosen as the ABL on the surface and the HPL on the bottom, between which nonwoven incorporated bacterial cellulose (BC/PETN) as the HPL was intercalated to enhance the mechanical property. Photodynamic antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa was confirmed by the enlarged inhibition zones; meanwhile, satisfactory biocompatibility of the HPL was verified by scanning electronic microscopy (SEM) of L929 cells cultured on its surface. The potential effects on wound healing in a mice skin defect model of the MC membranes were also evaluated. The animal experiments demonstrated that the wound healing rate in the MC group was significantly increased compared with that in the control group (p < 0.05). Histopathological observation revealed an alleviated inflammatory response, accompanied with vascular proliferation in the MC group. The MC membranes significantly promoted wound healing by creating an antibacterial environment and promoting angiogenesis. Taken together, this MC membrane may act as a promising wound dressing for skin wound healing.

2.
Cell Mol Immunol ; 17(3): 305-306, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32071419

RESUMO

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

3.
J Mater Chem B ; 8(11): 2350-2362, 2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32104824

RESUMO

Mineralised collagen fibrils constitute the basic building blocks of bone, dentin and cementum. Noncollagenous proteins (NCPs) that are indispensable for collagen biomineralisation are not commercially available, and the mechanism of intrafibrillar mineralisation remains debatable. Herein, synthetic biomimetic molecules are regarded as alternative candidates for NCPs, and more convenient in revealing the mechanism of intrafibrillar mineralisation in vitro. Here, we fabricated a novel amphiphilic oligopeptide imitating a natural NCP. We aimed to investigate the effectiveness of the oligopeptide in intrafibrillar mineralisation and partially reveal the corresponding mechanism in vitro. The effectiveness of the oligopeptide in intrafibrillar mineralisation was characterised from the following aspects: (1) mineral interaction, (2) collagen binding and (3) induction of intrafibrillar mineralisation. Results indicated that the self-assembled oligopeptide could attract calcium ions inducing the formation of amorphous precursors; and bind onto the surface of collagen fibrils. These processes were mainly driven by the electrostatic attraction and hydrogen bonds. The self-assembled oligopeptide induced the intrafibrillar mineralisation of reconstituted collagen fibrils, in which the c-axis of apatite crystallites was roughly parallel to the long axis of the fibrils. The collagen mineralisation was achieved by binding with the self-assembled oligopeptide to increase the pool of mineralization precursors available for intrafibrillar mineralisation. In addition, the self-assembled oligopeptide induced dentin collagen remineralisation and formed a 30 µm-thick remineralised layer within 96 h. Our work sheds light on the fabrication of a novel biomimetic molecule for collagen mineralisation. The results should serve as a reference for understanding the mechanism of intrafibrillar mineralisation.

4.
J Ethnopharmacol ; 253: 112634, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32004628

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Flos Trollii is the dried flowers of Trollius chinensis. It has been used as a traditional herbal medicine for the treatment of upper respiratory tract infection, tonsillitis and pharyngitis in China for a long history. Veratric acid, vitexin, and trolline are the representative compounds of phenolic acids, flavonoids and alkaloids in this herbal medicine. All of these three compounds show antiviral activity which is related to the efficacy of Flos Trollii. AIM OF THE STUDY: To investigate the anti-influenza A virus mechanism of the three representative compounds from the perspective of regulating TLRs signaling pathways, so as to understand the relevant efficacy of Flos Trollii. MATERIALS AND METHODS: Influenza A virus A/FM/1/47 (H1N1) and mouse peritoneal macrophages (RAW264.7) were used in the whole process of investigation. MTT assay was conducted to select the appropriate experimental concentrations of the three compounds on RAW264.7 cells. Western blot, RT-PCR, and ELISA assays were performed to determine the protein and mRNA expression of key factors and related inflammatory factors of TLRs signaling pathways. Griess method was employed to detect the production of NO. RESULTS: The three representative compounds reduced the inflammatory factors including NO, IL-6, and TNF-α and enhanced the production of IFN-ß through dynamically regulating the TLRs 3, 4 and 7 pathways. Veratric acid significantly down-regulated the protein expression of TLR3 and IRF3 as well as the mRNA expression of TBK1 and TRIF. Vitexin significantly down-regulated the protein expression of TBK1 and IRF3 as well as the mRNA expression of TLR3, TBK1, TRIF and IRF3 while up-regulated the protein expression of TLR4 and IKKα. Trolline significantly down-regulated the protein expression of TLR7 whereas significantly up-regulated the protein expression of TLR4, IKKα and TAK1. CONCLUSIONS: The three representative compounds from Flos Trollii play their parts in anti-H1N1 viral effect through partially down-regulating TLRs 3 and 7 pathways and up-regulating TLR4 pathway. They counteract the inflammatory injury caused by excessive production of NO, IL-1, IL-6, and TNF-α induced by virus infection and enhance the production of IFN-ß so as to eliminate the virus.

5.
Food Nutr Res ; 642020.
Artigo em Inglês | MEDLINE | ID: mdl-32110174

RESUMO

Background: Recent evidence indicates that the inhibition of hepatocyte apoptosis is possible to develop a potential therapeutic strategy for nonalcoholic fatty liver disease (NAFLD). Our previous work suggested that purple sweet potato color (PSPC), a class of naturally occurring anthocyanins, effectively improved many features of high-fat diet (HFD)-induced NAFLD. However, whether PSPC ameliorates HFD-induced hepatocyte apoptosis has never been investigated. Objective: Here we investigated the effects of PSPC on HFD-induced hepatic apoptosis and the mechanisms underlying these effects. Design: Mice were divided into four groups: Control group, HFD group, HFD + PSPC group and PSPC group. PSPC was administered by daily oral gavage at doses of 700 mg/kg/day for 20 weeks. EX-527 (a SirT1-selective inhibitor) and Sirt1 siRNA were used to demonstrate the Sirt1 dependence of PSPC-mediated effects on apoptotic and survival signaling pathways in vivo and in vitro. Results: Our results showed that PSPC reduced body weights, hepatic triglyceride contents, histopathological lesions and serum ALT levels in a mouse model of NAFLD induced by HFD. Furthermore, PSPC attenuated HFD-induced hepatocyte apoptosis ratio from 7.27 ± 0.92% to 1.79 ± 0.27% in mouse livers, which is insignificant compared with that of controls. Moreover, PSPC activated Sirt1 by boosting NAD+ level in HFD-treated mouse livers. Furthermore, PSPC promoted Sirt1-dependent suppression of P53-mediated apoptotic signaling and activation of Akt survival signaling pathway in HFD-treated mouse livers, which was confirmed by EX527 treatment. Moreover, Sirt1 knockdown abolished these ameliorative effects of PSPC on apoptosis and P53 acetylation and protein expression in PA-treated L02 cells. Ultimately, PSPC reduced Caspase-3 activation and Bax level, and elevated the Bcl-2 level in HFD-treated mouse livers. Conclusion: PSPC protected against HFD-induced hepatic apoptosis by promoting Sirt1- dependent inhibition of p53-apoptotic pathway and facilitation of Akt survival pathway. This study indicates that PSPC is a candidate for nutritional intervention of NAFLD.

6.
Cell Commun Signal ; 18(1): 30, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093731

RESUMO

BACKGROUND: Candida albicans is the most common opportunistic human fungal pathogen. The chemokine ligand CXCL1 plays a protective role in fungal infection through the recruitment of neutrophils. TRAF1 (tumor necrosis factor-associated factor 1) can be highly induced by proinflammatory stimuli such as LPS and TNF and has been implicated in septic shock. However, the role of TRAF1 in infection, especially fungal infection, remains elusive. Herein, we reveal that TRAF1 suppresses the antifungal immune response to Candida albicans intradermal infection through the regulation of CXCL1 induction and neutrophil recruitment. METHODS: A mouse model of C. albicans intradermal infection was established. The Traf1-/- mice and Traf1-/- immortalized human keratinocytes were generated. The p65 inhibitor triptolide, STAT1 inhibitor fludarabine, neutrophil-depletion antibody Ly6G, and neutralizing antibody for CXCL1 were utilized. The expression of proinflammatory cytokines and chemokines was assessed by real-time PCR and ELISA, and the activation of signaling molecules was analyzed by Western blotting. Hematoxylin and eosin staining and periodic acid Schiff staining were used for histology or fungal detection, respectively. The immunofluorescence and flow cytometry analyses were employed in the assessment of immune cell infiltration. Bone marrow transplantation and adoptive transfer experiments were conducted to establish a role for TRAF1 in the macrophage compartment in fungal skin infection. RESULTS: TRAF1-deficient mice demonstrated improved control of Candida albicans intradermal infection, and concomitant increase in neutrophil recruitment and reduction in fungal burden. The chemokine CXCL1 was upregulated in the TRAF1-deficient macrophages treated with heat-killed C. albicans. Mechanistically, TRAF1-deficient macrophages showed increased activation of transcription factor NFκB p65. The human CXCL8 was also highly induced in the TRAF1-deficient human keratinocytes upon TNF stimulation through decreasing the activation of transcription factor STAT1. TRAF1-deficient macrophages played a critical role in containing the C. albicans skin infection in vivo. CONCLUSION: TRAF1-deficient mice can better control fungal infection in the skin, a process attributable to the CXCL-neutrophil axis. Mechanistically, TRAF1 likely regulates CXCL1 expression in both macrophages and keratinocytes through the transcriptional factor NFκB and STAT1, respectively. Our finding offers new insight into the understanding of the immune regulatory mechanisms in host defense against C. albicans infection.

7.
Org Biomol Chem ; 18(8): 1607-1611, 2020 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-32030393

RESUMO

An enantioselective (92-99% ee) Michael/aldol cascade reaction between 4,4,4-trifluoroacetoacetates and α,ß-unsaturated enones was established in the presence of cinchona alkaloid-based primary amines. Various ß-CF3-cyclohexanones were constructed in high yields (81-99%) as a couple of separable diastereomers. This tandem reaction was sensitive to acidic co-catalysts, with a Michael/aldol condensation process favorably occurring to generate ß-CF3-cyclohexenones (42-69% yield, 84-96% ee) in the presence of trifluoroacetic acid.

8.
Oxid Med Cell Longev ; 2020: 9741369, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31998447

RESUMO

Spinal cord injury (SCI) is a devastating disease that may lead to lifelong disability. Thus, seeking for valid drugs that are beneficial to promoting axonal regrowth and elongation after SCI has gained wide attention. Metformin, a glucose-lowering agent, has been demonstrated to play roles in various central nervous system (CNS) disorders. However, the potential protective effect of metformin on nerve regeneration after SCI is still unclear. In this study, we found that the administration of metformin improved functional recovery after SCI through reducing neuronal cell apoptosis and repairing neurites by stabilizing microtubules via PI3K/Akt signaling pathway. Inhibiting the PI3K/Akt pathway with LY294002 partly reversed the therapeutic effects of metformin on SCI in vitro and vivo. Furthermore, metformin treatment weakened the excessive activation of oxidative stress and improved the mitochondrial function by activating the nuclear factor erythroid-related factor 2 (Nrf2) transcription and binding to the antioxidant response element (ARE). Moreover, treatment with Nrf2 inhibitor ML385 partially abolished its antioxidant effect. We also found that the Nrf2 transcription was partially reduced by LY294002 in vitro. Taken together, these results revealed that the role of metformin in nerve regeneration after SCI was probably related to stabilization of microtubules and inhibition of the excessive activation of Akt-mediated Nrf2/ARE pathway-regulated oxidative stress and mitochondrial dysfunction. Overall, our present study suggests that metformin administration may provide a potential therapy for SCI.

9.
J Comput Biol ; 27(1): 55-68, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31424286

RESUMO

Adamantinomatous craniopharyngioma (ACP) is a congenital epithelial tumor in the sellar region with benign histological manifestation but invasive. Currently, surgery is the main treatment for it, but its recurrence rate is high. Therefore, it is of great importance to explore the mechanism of occurrence and development of ACP and to identify new molecules. One gene expression profile, GSE94349, was downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by the limma package. Gene set enrichment analysis was used to make enrichment analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Then, we performed the construction and analysis of the protein-protein interaction (PPI) network and significant module. The analysis of the GSE94349 dataset identified 109 DEGs, consisting of 80 upregulated genes and 29 downregulated genes in ACP samples compared with normal brain tissues. Functional and pathway enrichment analysis of DEGs provided a comprehensive overview of some major pathophysiological mechanisms in ACP: RNA polymerase II promoter, glutamate receptor binding, and so on. A total of 10 hub genes of DEGs were obtained from the PPI network, which provided potential therapeutic targets for the ACP. In summary, there were DEGs between ACP tissues and normal brain tissues, which may be involved in the mechanisms of occurrence and development of ACP, especially via the regulation of RNA polymerase II promoter and glutamate receptor binding. Key genes in DEGs could serve as new research targets for the diagnosis and treatment of ACP.

10.
Exp Cell Res ; 386(2): 111740, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31756312

RESUMO

Advanced gastric cancer (GC) is aggressive with a high mortality rate. Rhesus family, C glycoprotein (RhCG) participates in tumor progression in many cancers, however its function in GC is still unknown. Here, we showed that RhCG was overexpressed in GC tissues at mRNA (P = 0.036) and protein levels (P < 0.05) compared with normal tissues. High RhCG level was correlated with poor differentiation (P = 0.037), TNM stage (P < 0.001), high HER-2 level (P = 0.018) and worse prognosis (P < 0.001). Cox proportional hazard model indicated that RhCG level was an independent prognostic biomarker. RhCG knockdown significantly decreased pHi and impeded tumor cellular proliferation, migration and invasion and repressed ß-catenin and c-myc expression in GC cells. Moreover, GC cells with high RhCG level had reduced oxaliplatin efficacy suggesting a role for RhCG as a therapeutic target for GC. Our findings revealed a function of RhCG in cancer pathogenesis, invasion and metastasis in human GC. We suggest that RhCG act may as a novel prognostic indicator and a therapeutic target for gastric adenocarcinoma.

11.
Environ Pollut ; 258: 113693, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31838391

RESUMO

2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) is associated with various adverse human health effects; however, the knowledge of its toxicity is still very limited. Mitochondrial injury has been observed in liver cells exposed to BDE-47 in vitro. Mitophagy impairment causes the accumulation of dysfunctional mitochondria, contributing to the pathological mechanisms of liver injury. The aim of this study was to investigate whether BDE-47 impairs mitophagy to trigger mitochondrial dysfunction-related liver injury and the underlying mechanisms. This study revealed that BDE-47 elicited mitochondrial dysfunction and related oxidative liver injury by impairing mitophagy. Moreover, our results showed that NAD+ insufficiency is responsible for BDE-47-mediated mitophagy defect and mitochondrial dysfunction in mouse livers, which was associated with suppression of Sirt3/FoxO3a/PINK1 signaling. Furthermore, our results indicated a potential role of miR-34a-5p in the hepatotoxicity of BDE-47. Mechanistically, BDE-47 dramatically upregulated miR-34a-5p expression in mouse livers. The data from AAV-sponge-mediated miR-34a-5p inhibition suggested that miR-34a-5p diminished NAD+ level by directly targeting NAMPT expression in BDE-47-treated mouse livers, which was confirmed by luciferase reporter assay. Consequently, miR-34a-5p markedly abated Sirt3/FoxO3a/PINK1 signaling-mediated mitophagy to promote mitochondrial dysfunction in BDE-47-treated mouse livers. The present study provided in vivo evidence to reveal a potential mechanism for BDE-47-induced mitochondrial dysfunction and related liver injury and indicated that miR-34a-5p-mediated mitophagy impairment might be a therapeutic target for BDE-47 toxicity.

12.
Chemosphere ; 238: 124634, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31473525

RESUMO

A cavity attenuated phase shift single scattering albedo monitor was set up on a tethered airship platform to study the vertical profiles of particle light extinction coefficient (bext) in the lower troposphere (<1000 m) in Shanghai during 12-29 December 2015. Clear transition heights (THs) for vertical profiles of bext during the polluted days (PM2.5 > 75 µg m-3) were observed below 1000 m. The vertical differences of bext were highly dynamic as the vertical variation in bext was significant by as much as 605 Mm-1. The TH was observed mostly at about 100-200 m, and 450-650 m during night and daytime, respectively, and was in a wide range of ∼50-900 m during 15:00-22:00 due to the low boundary layer and/or the transport of pollutants. In particular, the TH was consistently below 500 m throughout the day during highly polluted haze episodes, highlighting the important role of a stagnant atmosphere situation for high concentrations of PM2.5. The vertical distribution of bext did not have a constant rule with respect to relative humidity and wind. Sometimes, peak values of bext at ∼350 m and 500 m during daytime were caused by enhanced regional transport. During stagnant and highly polluted situations or well-mixed clean days, bext was usually uniformly distributed below and above the TH, respectively, although bext was much smaller above the TH. For other situations, local emissions, pollutant transport, and the physical and chemical characteristics of aerosols resulted in highly dynamic vertical profiles of bext.


Assuntos
Poluentes Atmosféricos/análise , Atmosfera/química , Monitoramento Ambiental/métodos , Material Particulado/análise , Aerossóis/análise , China , Estações do Ano , Vento
13.
ISA Trans ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31812248

RESUMO

With the rapid development of China's industrialization, the air pollution is becoming more and more serious. It is vital for us to predict the air quality for determining the further prevention measures of avoiding the brought disasters. In this paper, we are going to propose an approach of predicting the air quality based on the multiple data features through fusing the multiple machine learning models. The approach takes the meteorological data and air quality data for the past six days as one batch of input (the whole data set is for 46 days) and employs a multi-model fusion to provide an improved 24-hour prediction of PM2.5 pollutant concentration all over Beijing. During the above process, two focal feature groups are composed. The first focal feature group contains the historical meteorological data, while the second group includes the statistical information, the date information and the polynomial variations. Besides the two groups, we complement one million more data items by employing the time sliding means. Among the supplementary data, we select the most critical 500 features with Light Gradient Boosting Machine (LightGBM) model and send the features as the input to Gradient Boosting Decision Tree (GBDT) and LightGBM models. Meanwhile, we screen the most critical 300 features with eXtreme Gradient Boosting (XGBoost) model and send them as the input to the three prediction models. Referring to each of the models, we respectively gain the optimal parameters through grid search methods and then fuse the models' contribution with the linear weighting. The experiments indicate that the proposed approach based on the weighting fusion is better than that provided by a single modeling scheme, and the loss value is 0.4158 under the SMAPE index.

14.
ACS Appl Mater Interfaces ; 11(47): 44153-44160, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31702126

RESUMO

Highly efficient catalysts for both oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are key to the commercialization of rechargeable zinc-air batteries (ZABs). In this work, a catalyst with uniform nanospherical morphology was prepared from cobalt nitrate, acetylacetone, and hydrazine hydrate. The final catalyst possesses high ORR and OER performances, with a half-wave potential of 0.911 V [vs reversible hydrogen electrode (RHE)] for ORR and a low potential of 1.57 V (vs RHE) at 10 mA cm-2 for OER in 0.1 M KOH solution. Specially, a ZAB based on the catalyst demonstrates an ultrahigh power density of 479.1 mW cm-2, as well as excellent stability, and potential in practical applications.

15.
Medicine (Baltimore) ; 98(45): e17852, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702645

RESUMO

RATIONALE: Fusidic acid (FA) is an active agent against gram-positive bacteria such as Staphylococcus, it is generally well tolerated and the major adverse effects are mild gastrointestinal discomfort, diarrhea, and headache. However, some rare side effects such as granulocytopenia and thrombocytopenia have also been reported. Here we report a case of FA-induced hepatotoxicity and hematologic toxicity. PATIENT CONCERNS: A 54-year-old woman with hepatitis B cirrhosis was referred to us because of fever, Staphylococcus aureus was identified in the twice blood culture, and intravenous FA was given (0.5 g, q8 hours). Twelve days after FA therapy, she developed nausea and jaundice. Meanwhile, complete blood cell count showed neutropenia (white blood cell count of 1360/µL, neutrophil of 619/µL) and aggravated thrombocytopenia (platelet count of 18,000/µL). Adverse drug reaction was suspected, and FA was stopped immediately, after 1 day of discontinuation of FA, nose bleeding occurred and the platelet count declined further and reached the lowest value of 4000/µL. DIAGNOSES: Hepatotoxicity and hematologic complications induced by FA were diagnosed. INTERVENTIONS AND OUTCOMES: The FA was stopped immediately, and concentrated platelet transfusion was used. Five days after withdrawal of FA, jaundice resolved and the hematologic index returned to the level before the medication. LESSONS: Hematologic adverse effect accompanying with hepatotoxicity may be induced by FA. Though the risk is rather low, it should not be overlooked.


Assuntos
Ácido Fusídico/administração & dosagem , Icterícia/induzido quimicamente , Neutropenia/induzido quimicamente , Infecções Estafilocócicas/tratamento farmacológico , Administração Intravenosa , Feminino , Ácido Fusídico/efeitos adversos , Hepatite B/complicações , Humanos , Cirrose Hepática/virologia , Pessoa de Meia-Idade , Neutropenia/terapia , Transfusão de Plaquetas , Infecções Estafilocócicas/diagnóstico , Staphylococcus aureus/isolamento & purificação , Resultado do Tratamento
16.
Br J Cancer ; 121(12): 1039-1049, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31690832

RESUMO

BACKGROUND: Tamoxifen resistance remains a significant clinical challenge for the therapy of ER-positive breast cancer. It has been reported that the upregulation of transcription factor SOX9 in ER+ recurrent cancer is sufficient for tamoxifen resistance. However, the mechanisms underlying the regulation of SOX9 remain largely unknown. METHODS: The acetylation level of SOX9 was detected by immunoprecipitation and western blotting. The expressions of HDACs and SIRTs were evaluated by qRT-PCR. Cell growth was measured by performing MTT assay. ALDH-positive breast cancer stem cells were evaluated by flow cytometry. Interaction between HDAC5 and SOX9 was determined by immunoprecipitation assay. RESULTS: Deacetylation is required for SOX9 nuclear translocation in tamoxifen-resistant breast cancer cells. Furthermore, HDAC5 is the key deacetylase responsible for SOX9 deacetylation and subsequent nuclear translocation. In addition, the transcription factor C-MYC directly promotes the expression of HDAC5 in tamoxifen resistant breast cancer cells. For clinical relevance, high SOX9 and HDAC5 expression are associated with lower survival rates in breast cancer patients treated with tamoxifen. CONCLUSIONS: This study reveals that HDAC5 regulated by C-MYC is essential for SOX9 deacetylation and nuclear localisation, which is critical for tamoxifen resistance. These results indicate a potential therapy strategy for ER+ breast cancer by targeting C-MYC/HDAC5/SOX9 axis.

17.
Cell Mol Immunol ; 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31767975

RESUMO

Innate immunity plays a prominent role in the host defense against pathogens and must be precisely regulated. As vital orchestrators in cholesterol homeostasis, microRNA-33/33* have been widely investigated in cellular metabolism. However, their role in antiviral innate immunity is largely unknown. Here, we report that VSV stimulation decreased the expression of miR-33/33* through an IFNAR-dependent manner in macrophages. Overexpression of miR-33/33* resulted in impaired RIG-I signaling, enhancing viral load and lethality whereas attenuating type I interferon production both in vitro and in vivo. In addition, miR-33/33* specifically prevented the mitochondrial adaptor mitochondrial antiviral-signaling protein (MAVS) from forming activated aggregates by targeting adenosine monophosphate activated protein kinase (AMPK), subsequently impeding the mitophagy-mediated elimination of damaged mitochondria and disturbing mitochondrial homeostasis which is indispensable for efficient MAVS activation. Our findings establish miR-33/33* as negative modulators of the RNA virus-triggered innate immune response and identify a previously unknown regulatory mechanism linking mitochondrial homeostasis with antiviral signaling pathways.

18.
Zootaxa ; 4564(2): zootaxa.4564.2.10, 2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-31716509

RESUMO

The new species, Hilethera xinjiangensis sp. nov. (Orthoptera: Acrididae: Oedipodinae) is described based on specimens collected from Xinjiang, northern China. The new species is similar to H. brevipennis Zheng Lu, 2002 and H. turanica Uvarov, 1925, but differs from: (1) dark brown in general coloration, (2) darker coloration in forewings, (3) forewings longer than H. brevipennis but shorter than H. turanica, (4) cubital area of forewings boarder than H. brevipennis and H. turanica, (5) hind tibiae dark brown with two light yellow pre-basal rings, while dark with one fade pre-basal ring in H. brevipennis and light yellow with three dark rings in H. turanica.In addition, the complete mitogenome of holotype was sequenced using next-generation sequencing technology. The total length of the assembled mitogenome is 16,145 bp, representing 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes and one noncoding region (D-loop region). The new mitogenome sequence is compared with published Oedipodinae mitogenomes and the phylogenetic relationships within the subfamily are reconstructed. The results infer that the gene cox1 could be a useful marker for higher phylogenetic level, while the genes nd5 and rrnL could be potentially useful markers between closely related species.


Assuntos
Genoma Mitocondrial , Gafanhotos , Ortópteros , Animais , China , Gafanhotos/genética , Ortópteros/genética , Filogenia , RNA Ribossômico , RNA de Transferência
19.
Environ Pollut ; 255(Pt 2): 113345, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31610508

RESUMO

Despite substantial mitigation of particulate matter (PM) pollution during the past decade in Beijing, the response of aerosol chemistry to clean air action and meteorology remains less understood. Here we characterized the changes in aerosol composition as responses to emission reductions by using two-year long-term measurements in 2011/2012 and 2017/2018, and WRF-Chem model. Our results showed substantial decreases for all aerosol species except nitrate from 2011/2012 to 2017/2018. Chloride exhibited the largest decrease by 65-89% followed by organics (37-70%), mainly due to reductions in coal combustion emissions in winter and agriculture burning in June. Primary and secondary organic aerosol (SOA) showed comparable decreases by 61-70% in fall and winter, and 34-63% in spring and summer, suggesting that reductions in primary emissions might also suppress SOA formation. The changes in nitrate were negligible and even showed increases due to less reductions in NOx emissions and increased formation potential from N2O5 heterogeneous reactions. As a result, nitrate exceeded sulfate and became the major secondary inorganic aerosol species in PM with the contribution increasing from 14-21% to 22-32%. Further analysis indicated that the reductions in aerosol species from 2011/2012 to 2017/2018 were mainly caused by the decreases of severely polluted events (PM1 > 100 µg m-3). WRF-Chem simulations suggested that the decreases in OA and sulfate in fall and winter were mainly resulted from emission reductions (27-36% and 25-43%) and favorable meteorology (4-10% and 19-30%), while they were dominantly contributed by emission changes in spring and summer. Comparatively, the changes in nitrate were mainly associated with meteorological variations while the contributions of emissions changes were relatively small. Our results highlight different chemical responses of aerosol species to emission changes and meteorology, suggesting that future mitigation of air pollution in China needs species-targeted control policy.


Assuntos
Aerossóis/análise , Poluentes Atmosféricos/análise , Poluição do Ar/estatística & dados numéricos , Monitoramento Ambiental , Material Particulado/análise , Poluição do Ar/análise , Pequim , China , Óxidos de Nitrogênio/análise , Estações do Ano , Sulfatos/análise
20.
Artif Cells Nanomed Biotechnol ; 47(1): 4001-4011, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31588803

RESUMO

Triple-negative breast cancer (TNBC) stands for a refractory subtype, which predicts poor prognosis and has no effective therapies yet for improving it. Given the restrictions of traditional treatments, novel therapeutic strategies need excavating to alleviate the intrinsic or acquired resistance. Ribociclib, a selective CDK4/6 inhibitor, has successfully prevented cancers from deteriorating by intervening the CDK4/6-cyclin D-Rb-E2F pathway, especially for estrogen receptor-positive (ER +) breast cancer. However, there still remains limited accessibility referring to TNBC. Performing experiments on MDA-MB-231 cells, we found that LEE011 could suppress cell proliferation, and this suppression tended to be dose-dependently. Western blotting analysis presented significant decrease with the expression of CDK4/6 after LEE011 treated, and other proteins associated with this axis such as cyclin D1, p-Rb, Rb, E2F1 showed aberrant changes. Moreover, LEE011 induced G0-G1 phase cell cycle arrest, promoted cell apoptosis, and reduced cell migration in vitro. In addition, tumor growth was remarkably impeded without obvious side-effects in MDA-MB-231 xenograft models. Our research has identified that LEE011 was not completely invalid for MDA-MB-231. Considering its pivotal status in TNBC, the CDK4/6-cyclin D-Rb-E2F pathway informed us the possibility and practicality of Ribociclib (LEE011) as pharmacological intervention, but challenges warrant further validation in prospective studies.


Assuntos
Aminopiridinas/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Proteínas Inibidoras de Quinase Dependente de Ciclina/farmacologia , Purinas/farmacologia , Aminopiridinas/uso terapêutico , Animais , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Ciclina D1/metabolismo , Quinase 4 Dependente de Ciclina/metabolismo , Quinase 6 Dependente de Ciclina/metabolismo , Proteínas Inibidoras de Quinase Dependente de Ciclina/uso terapêutico , Fator de Transcrição E2F1/metabolismo , Feminino , Humanos , Masculino , Neoplasias Mamárias Experimentais , Camundongos , Camundongos Nus , Fosforilação/efeitos dos fármacos , Purinas/uso terapêutico , Proteína do Retinoblastoma/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Carga Tumoral/efeitos dos fármacos
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