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1.
Allergy ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33022771

RESUMO

BACKGROUND: Although the importance of ectopic lymphoid tissues (eLTs) in the pathophysiology of nasal polyps (NPs) is increasingly appreciated, the mechanisms underlying their formation remain unclear. OBJECTIVE: To study the role of interleukin (IL)-17A, C-X-C motif chemokine ligand 13 (CXCL13), and lymphotoxin (LT) in eLT formation in NPs. METHODS: The expression levels of CXCL13 and LT and their receptors, in addition to the phenotypes of stromal cells in NPs, were studied by flow cytometry, immunostaining, and real-time reverse transcription-polymerase chain reaction (RT-PCR). Purified nasal stromal cells and B cells were cultured and a murine model of nasal type 17 inflammation was established by intranasal curdlan challenge for the mechanistic study. RESULTS: The excessive CXCL13 production in NPs correlated with enhanced IL-17A expression. Stromal cells, with CD31- Pdpn+ fibroblastic reticular cell (FRC) expansion, were the major source of CXCL13 in NPs without eLTs. IL-17A induced FRC expansion and CXCL13 production in nasal stromal cells. In contrast, B cells were the main source of CXCL13 and LTα1 ß2 in NPs with eLTs. CXCL13 upregulated LTα1 ß2 expression on B cells, which in turn promoted CXCL13 production in nasal B cells and stromal cells. LTα1 ß2 induced expansion of FRCs and CD31+ Pdpn+ lymphoid endothelial cells, which were the predominant stromal cell types in NPs with eLTs. IL-17A knockout and CXCL13 and LTßR blockage diminished nasal eLT formation in the murine model. CONCLUSION: We identified an important role of IL-17A-induced stromal cell remodeling in the initiation and crosstalk between B and stromal cells via CXCL13 and LTα1 ß2 in the enlargement of eLTs in NPs.

2.
Can J Vet Res ; 84(4): 283-293, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33012977

RESUMO

In this study, we investigated whether ß-glucan from Saccharomyces cerevisiae exerts beneficial effects on mucosal immunity in an ovine ruminal explant (ORE) model. Once the ORE model was established, viability was assessed through histological change, E-cadherin expression, CK-18 and Ki-67 distribution. Then, the OREs were co-cultured with ß-glucan, following which, gene and protein expression levels of sheep ß-defensin-1 (SBD-1), pro-inflammatory interleukin (IL)-6, and anti-inflammatory IL-10 were detected using quantitative real-time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). Hematoxylin & eosin staining, qPCR, and immunohistochemistry showed that the overall ORE structure was intact after 96 hours in culture, but explants cultured for more than 24 hours showed epithelial degradation. Therefore, we performed the follow-up test within 24 hours. qPCR and ELISA revealed that the gene and protein expression levels of SBD-1, IL-6, and IL-10 in the OREs significantly increased (P < 0.05) after treatment with ß-glucan compared with controls. This study identified the feasibility and optimal conditions of ORE culture and demonstrated that ß-glucan activates SBD-1, IL-6, and IL-10 secretion in OREs to promote mucosal immunity.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33012136

RESUMO

BACKGROUND: In this study we aimed to identify inflammatory patterns and predictors associated with clinical outcomes in chronic rhinosinusitis with nasal polyps (CRSwNP) patients with different blood and tissue eosinophilia. METHODS: A total of 535 CRSwNP patients were enrolled, and the expression of 35 biomarkers, together with eosinophil and neutrophil counts in nasal polyps, were analyzed in a subset of 249 patients. Patients were stratified on the basis of blood (≥0.5 × 109 /L) and tissue (>10%) eosinophilia. Logistic regression models were applied to identify predictors of uncontrolled disease at least 1 year after surgery. Uncontrolled disease was defined according to the European Position Paper on Rhinosinusitis and Nasal Polyps 2020. RESULTS: Among 535 patients, 38.5% showed inconsistent blood and tissue eosinophilia. In 249 CRSwNP patients, subjects with concomitant blood and tissue eosinophilia (group 1) showed marked mucosal type 2 inflammation, characterized by high levels of interleukin (IL)-5, IL-13, and eotaxin-1, whereas subjects with normal blood and tissue eosinophil levels (group 4) demonstrated significant local neutrophilic inflammation with high expression of granulocyte colony-stimulating factor and subjects with selective tissue eosinophilia (group 2) showed intermediate and mixed eosinophilic and neutrophilic inflammation. Subjects with isolated blood eosinophilia (group 3) showed low expression of vascular endothelial growth factor and IL-10. Asthma, prior sinus surgery, and blood eosinophilia were the top 3 predictors for postsurgical uncontrolled disease. For subgroup analysis, sex in group 1, asthma in group 2, tissue IL-10 and immunoglobulin E in group 3, and prior sinus surgery in group 4 were the strongest predictors of uncontrolled disease, respectively. CONCLUSION: Different blood and tissue eosinophilia revealed distinct tissue inflammatory patterns in CRSwNP patients.

4.
Discov Med ; 29(157): 129-137, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33002409

RESUMO

Sepsis is a life-threatening clinical condition demanding accurate and rapid diagnosis of the culprit pathogen, thereby to improve prognosis. Pathogen determination through blood culture is the gold standard for diagnosis but has limitations due to low sensitivity. Recently, circulating DNAs derived from pathogenic organisms were found in the plasma of patients with sepsis and were further proved to be more sensitive biomarkers for the diagnosis of the pathogen origin in sepsis. However, the fundamental molecular characteristics of circulating DNA in patients with sepsis remain unclear. Here, we used specific PCR and Sanger sequencing to verify the microbiology culture results via the corresponding plasma circulating DNA. We analyzed the composition and molecular characteristics of circulating DNA in septic patients using next-generation sequencing technology. We showed the presence of pathogen-derived circulating DNA in the plasma of patients with sepsis. The sizes of circulating DNA fragments derived from pathogenic bacteria showed a skewed unimodal distribution, while those derived from host cells showed a normal unimodal distribution. Lengths of fragments at peak concentration for both origins ranged from 150 bp to 200 bp, and reads mapping to pathogenic bacteria genome distributed uniformly on the reference. Our findings have improved our understanding of microbial circulating DNA in patients with sepsis as a potential methodology for the accurate diagnosis of sepsis, especially in light of an urgent need for such a diagnosis associated with the COVID-19 infection.


Assuntos
Infecções Bacterianas/microbiologia , Ácidos Nucleicos Livres/sangue , DNA Bacteriano/sangue , Sepse/microbiologia , Adulto , Idoso , Infecções Bacterianas/complicações , Infecções Bacterianas/diagnóstico , Betacoronavirus , Ácidos Nucleicos Livres/análise , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Técnicas de Cultura , DNA Bacteriano/análise , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Pandemias , Pneumonia Viral , Reação em Cadeia da Polimerase , Sepse/complicações , Sepse/diagnóstico , Análise de Sequência de DNA
5.
J Immunol Res ; 2020: 4594630, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029540

RESUMO

Objectives: Both thymic stromal lymphopoietin (TSLP) and dendritic cells (DCs) are involved in many autoimmune diseases, but the potential roles of TSLP and DCs in bullous pemphigoid (BP) have not been clarified. We sought to explore the contributions of TSLP and DCs in patients with BP. Methods: TSLP levels in sera and blister fluids were measured by enzyme-linked immunosorbent assay. The TSLP expression in the BP lesional skin was detected by immunohistochemical staining. Infiltration of DCs, marked by DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), and its relationship with TSLP and TSLP receptors was evaluated by immunofluorescence staining. Results: We found that TSLP levels in sera and in blister fluids of patients with BP were higher compared to the control groups. In patients with BP, TSLP levels in sera correlated with TSLP levels in blisters. The expression of TSLP in the BP lesional skin was higher compared to the healthy controls' skin. Greater numbers of TSLP-positive cells were observed in the epidermis of patients with BP compared to the healthy controls. Greater numbers of DC-SIGN-positive cells were present in the BP lesional skin compared to the skin of controls. The expression of TSLP was highly upregulated in DC-SIGN-positive cells, and most DC-SIGN-positive cells expressed TSLP receptors. Conclusions: We conclude that TSLP may activate DC-SIGN-positive DCs directly, which may be involved in the pathogenesis of BP.

6.
Biomaterials ; 266: 120400, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33022477

RESUMO

It remains a major challenge to develop an effective therapeutic system based on gold nanorods (GNRs) for cancer therapy. Herein, we developed a redox-responsive, in-situ polymerized polyplatinum(IV)-coated gold nanorod (GNR@polyPt(IV)) with coupling of the near-infrared (NIR)-induced hyperthermal effect and redox-triggered drug release in one therapeutic platform as an amplifier of tumor accumulation through mild hyperthermia for enhanced synergistical thermo-chemotherapy. After in-situ polymerized with 2-methacryloyloxy ethyl phosphorylcholine (MPC) and Pt(IV) complex-based prodrug monomer (PPM) onto the surface of GNRs, the nanosized GNR@polyPt(IV) exhibited the advantages of high drug encapsulation efficiency, triggered drug release, and reduced side effect. As demonstrated by thermal imaging and photoacoustic imaging in vitro and in vivo, this GNR@polyPt(IV) exhibited an excellent NIR-associated hyperthermal effect and outstanding capacity of tumor accumulation. Importantly, under a mild hyperthermia process, the vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) were upregulation, resulting in angiogenic vessel around the tumor. Combination with accelerated blood flow and angiogenesis by mild hyperthermia, a dramatic increase of drug accumulation in tumor could be realized after systematic administration. As a result, this amplification fashion of tumor accumulation would contribute the GNR@polyPt(IV) to inhibit tumor progression effectively. Such a facile and simple methodology for enhanced therapeutic effect based on GNRs holds great promises for cancer therapy with further development.

7.
ACS Nano ; 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32965103

RESUMO

The TiO2/Au nanostructure has been acknowledged as one of the most classic visible-light active photocatalysts due to the surface plasmon resonance (SPR) of Au nanoparticles. In many cases, the SPR effect only features weak visible light absorption in conventional TiO2/Au nanostructures. Here, we demonstrate a design of TiO2/Au/TiO2 with a combination of whispering gallery mode (WGM) resonances and SPR for efficient visible-light-driven photocatalysis. Escherichia coli (E. coli) were used as natural reactants as well as a template to construct an E. coli-like TiO2/Au/TiO2 nanostructure. Using numerical simulations, we show that the E. coli-like TiO2 capsule acts as the WGM resonator to interplay with the SPR effect of the Au NPs on TiO2 surface, which leads to a significant increase of visible light absorption and the local field enhancement at the Au-TiO2 interface. Accordingly, with the synergistic effect of WGM and SPR, the E. coli-like TiO2/Au/TiO2 nanostructure exhibits enhanced photocatalytic activity in the visible range. Our work reveals a promising bioapproach to a design highly visible light active plasmonic photocatalyst.

8.
J Pharm Sci ; 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32946897

RESUMO

In this study, three different chitosan, namely carboxymethyl chitosan (CMC), hydroxypropyl chitosan (HPC) and trimethyl chitosan (TMC) were used as cationic materials to prepare tetrandrine lipid nanoparticles (TET-LNPs) for the treatment of glaucoma. In vitro drug release and pre-corneal retention were used to select the optimal chitosan. In vitro drug release curves of three kinds of LNPs showed a sustained release and TMC-TET-LNPs were the slowest. Moreover, compared with CMC-TET-LNPs and HPC-TET-LNPs, TMC-TET-LNPs had longer corneal retention time. Afterwards, the characteristics of TMC-TET-LNPs were investigated. The ocular irritation study revealed no sign of irritation in rabbit eyes. The pharmacokinetic studies showed that the area under the curve of TMC-TET-LNPs was increased by 2.03 times than TET solution (p < 0.01). Furthermore, the drug biofilm interactions were evaluated by molecular dynamics (MD) simulation. In MD simulation, the strong hydrophobic group of TET interacted with the tail of POPC, making it hard to enter the hydrophobic region of the membrane, thereby restricting TET ocular bioavailability. The experiments and MD simulation indicated that TMC-TET-LNPs had great potential for ocular administration and MD simulation could predict transmembrane transport of drugs.

9.
Chin J Acad Radiol ; : 1-5, 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32864570

RESUMO

To determine changes in clinical and radiologic findings associated with Coronavirus disease 2019 (COVID-19) from diagnosis to recovery, we retrospectively reviewed the diagnosis and treatment records of the first patient cured of COVID-19 in Guangzhou. A 55-year-old woman from Wuhan was admitted to the hospital isolation ward with the chief complaint of "cough for 11 days and once fever 8 days ago" on January 22, 2020. COVID-19 was laboratory confirmed by reverse transcription polymerase chain reaction (RT-PCR) assay, and she received conventional antiviral therapy, such as moxifloxacin, traditional Chinese medicine, and arbidol. Repeat chest-computed tomography (CT) scans were performed on days 13 and 19 of her illness. The former showed radiologic findings, including ground-glass opacities (GGOs), which revealed viral pneumonia; the latter revealed that the previous lesions had been significantly absorbed. The lesions on CT scans were consistent with the changes in the course of disease. Some drugs, such as traditional Chinese medicine and arbidol, might play an important role in the recovery of COVID-19 patients. This study provides some new insights into the formulation of a timely and effective diagnostic and therapeutic strategy to cure patients with COVID-19.

10.
J Am Soc Nephrol ; 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32912934

RESUMO

BACKGROUND: Eighteen known susceptibility loci for IgAN account for only a small proportion of IgAN risk. METHODS: Genome-wide meta-analysis was performed in 2628 patients and 11,563 controls of Chinese ancestry, and a replication analysis was conducted in 6879 patients and 9019 controls of Chinese descent and 1039 patients and 1289 controls of European ancestry. The data were used to assess the association of susceptibility loci with clinical phenotypes for IgAN, and to investigate genetic heterogeneity of IgAN susceptibility between the two populations. Imputation-based analysis of the MHC/HLA region extended the scrutiny. RESULTS: Identification of three novel loci (rs6427389 on 1q23.1 [P=8.18×10-9, OR=1.132], rs6942325 on 6p25.3 [P=1.62×10-11, OR=1.165], and rs2240335 on 1p36.13 [P=5.10×10-9, OR=1.114]), implicates FCRL3, DUSP22.IRF4, and PADI4 as susceptibility genes for IgAN. Rs2240335 is associated with the expression level of PADI4, and rs6427389 is in high linkage disequilibrium with rs11264799, which showed a strong expression quantitative trail loci effect on FCRL3. Of the 24 confirmed risk SNPs, six showed significant heterogeneity of genetic effects and DEFA showed clear evidence of allelic heterogeneity between the populations. Imputation-based analysis of the MHC region revealed significant associations at three HLA polymorphisms (HLA allele DPB1*02, AA_DRB1_140_32657458_T, and AA_DQA1_34_32717152) and two SNPs (rs9275464 and rs2295119). CONCLUSIONS: A meta-analysis of GWAS data revealed three novel genetic risk loci for IgAN, and three HLA polymorphisms and two SNPs within the MHC region, and demonstrated the genetic heterogeneity of seven loci out of 24 confirmed risk SNPs.  These variants may explain susceptibility differences between Chinese and European populations.

11.
Thorax ; 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963116
12.
Int J Biochem Cell Biol ; 128: 105859, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32987196

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly solid tumors in the world. Aerobic glycolysis is among the characteristic features of pancreatic cancer. However, the regulatory process of aerobic glycolysis in pancreatic cancer is too complicated, and the underlying mechanism remains unexplained. Reportedly, CDK4/6 inhibitors repress breast cancer cell proliferation by modulating glucose metabolism. Here, we reveal that the CDK4/6 inhibitor, PD0332991 stabilized FBP1 to hinder aerobic glycolysis in pancreatic cancer. We also show that the CDK4/6-E2 F1 signaling pathway mediated an increase in MAGED1 expression, promoting FBP1 degradation in pancreatic cancer. We, therefore, might have identified a novel mechanism by which the CDK4/6 inhibitor, PD0332991 blocks the Warburg effect of pancreatic cancer by stabilizing FBP1.

13.
Biosci Rep ; 40(9)2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32896857

RESUMO

The molecular weight of the polysaccharide and the chemical groups it contains has an important influence on its biological activity, relatively low molecular weight polysaccharides may have better antioxidant activity. Polysaccharides isolated from the fruiting bodies of Morchella sextelata (MSP) were treated by γ-irradiation at 10, 100 and 1000 kGy doses, and the physicochemical properties and antioxidant activity of irradiated MSP were investigated. Microscopic observation under a scanning electron microscope (SEM) showed that breakage and pores appeared on the surface of the irradiated polysaccharide. As the irradiation dose increased, the average molecular weight of MSP decreased significantly, while the particle size and thermal stability of MSP first increased at 10 and 100 kGy doses and then decreased at 1000 kGy doses. The antioxidant activities, measured by free radical scavenging tests and protective effect on PC12 cells injured by H2O2, were all increased after irradiation, especially when the concentration of MSP was low (50 and 100 µg/ml). Therefore, irradiation treatment was an effective method to enhance the activity of polysaccharides.

14.
Aging (Albany NY) ; 12(17): 17582-17600, 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32927432

RESUMO

The diabetes drug metformin has recently been shown to possess anti-cancer properties when used with other chemotherapeutic drugs. However, detailed mechanisms by which metformin improves cancer treatment are poorly understood. Here we provide evidence in HepG2 hepatocellular carcinoma cells that metformin sensitizes cisplatin-resistant HepG2 cells (HepG2/DDP) through increasing cellular glycolysis and suppressing Nrf2-dependent transcription. We show that metformin increases glucose uptake and enhances glucose metabolism through glycolytic pathway, resulting in elevated concentrations of intracellular NADPH and lactate. Consistently, high glucose medium suppresses Nrf2-dependent transcription and sensitizes HepG2/DDP cells to cisplatin. Elevated glycolysis was required for metformin to regulate Nrf2-dependent transcription and cisplatin sensitivity, as inhibition of glycolysis with 2-Deoxy-D-glucose (2-DG) significantly mitigates the beneficial effect of metformin. Together, our study has revealed an important biological process and gene transcriptional program underlying the beneficial effect of metformin on reducing chemo-resistance in HepG2 cells and provided new information on improving chemotherapy of liver cancers.

15.
Biomed Res Int ; 2020: 7021636, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32908907

RESUMO

As a natural polymer, gelatin is increasingly being used as a substitute for animals or humans for the simulation and testing of surgical procedures. In the current study, the similarity verification was neglected and a 10 wt.% or 20 wt.% gelatin sample was used directly. To compare the mechanical similarities between gelatin and biological tissues, different concentrations of gelatin samples were subjected to tensile, compression, and indentation tests and compared with porcine liver tissue. The loading rate in the three tests fully considered the surgical application conditions; notably, a loading speed up to 12 mm/s was applied in the indentation testing, the tensile test was performed at a speed of 1 mm/s until fracture, and the compression tests were compressed at a rate of 0.16 mm/s and 1 mm/s. A comparison of the results shows that the mechanical behaviors of low-concentration gelatin samples involved in the study are similar to the mechanical behavior of porcine liver tissue. The results of the gelatin material were mathematically expressed by the Mooney-Rivlin model and the Prony series. The results show that the material properties of gelatin can mimic the range of mechanical characteristics of porcine liver, and gelatin can be used as a matrix to further improve the similarity between substitute materials and biological tissues.

16.
Virol Sin ; 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32926330

RESUMO

H9N2 subtype avian influenza virus (AIV) is an influenza A virus that is widely spread throughout Asia, where it jeopardizes the poultry industry and provides genetic material for emerging human pathogens. To better understand the epidemicity and genetics of H9 subtype AIVs, we conducted active surveillance in live poultry markets (LPMs) in Hubei Province from 2013 to 2017. A total of 4798 samples were collected from apparent healthy poultry and environment. Real-time RT-PCR revealed that the positivity rate of influenza A was 26.6% (1275/4798), of which the H9 subtype accounted for 50.3% (641/1275) of the positive samples. Of the 132 H9N2 viral strains isolated, 48 representative strains were subjected to evolutionary analysis and genotyping. Phylogenetic analysis revealed that all H9N2 viral genes had 91.1%-100% nucleotide homology, clustered with genotype 57, and had high homology with human H9N2 viruses isolated from 2013 to 2017 in China. Using a nucleotide divergence cutoff of 95%, we identified ten distinct H9N2 genotypes that continued to change over time. Molecular analysis demonstrated that six H9N2 isolates had additional potential glycosylation sites at position 218 in the hemagglutinin protein, and all isolates had I155T and Q226L mutations. Moreover, 44 strains had A558V mutations in the PB2 protein and four had E627V mutations, along with H9N2 human infection strains A/Beijing/1/2016 and A/Beijing/1/2017. These results emphasize that the H9N2 influenza virus in Hubei continues to mutate and undergo mammalian adaptation changes, indicating the necessity of strengthening the surveillance of the AIV H9N2 subtype in LPMs.

17.
World J Gastroenterol ; 26(32): 4802-4816, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32921958

RESUMO

BACKGROUND: Multiple sites of metastasis and desmoplastic reactions in the stroma are key features of human pancreatic cancer (PC). There are currently no simple and reliable animal models that can mimic these features for accurate disease modeling. AIM: To create a new xenograft animal model that can faithfully recapitulate the features of human PC. METHODS: Interleukin 2 receptor subunit gamma (IL2RG) gene knockout Syrian hamster was created and characterized. A panel of human PC cell lines were transplanted into IL2RG knockout Syrian hamsters and severe immune-deficient mice subcutaneously or orthotopically. Tumor growth, local invasion, remote organ metastasis, histopathology, and molecular alterations of tumor cells and stroma were compared over time. RESULTS: The Syrian hamster with IL2RG gene knockout (named ZZU001) demonstrated an immune-deficient phenotype and function. ZZU001 hamsters faithfully recapitulated most features of human PC, in particular, they developed metastasis at multiple sites. PC tissues derived from ZZU001 hamsters displayed desmoplastic reactions in the stroma and epithelial to mesenchymal transition phenotypes, whereas PC tissues derived from immune-deficient mice did not present such features. CONCLUSION: ZZU001 hamsters engrafted with human PC cells are a superior animal model compared to immune-deficient mice. ZZU001 hamsters can be a valuable animal model for better understanding the molecular mechanism of tumorigenesis and metastasis and the evaluation of new drugs targeting human PC.

18.
Pestic Biochem Physiol ; 170: 104683, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32980051

RESUMO

Root rot caused by Cylindrocarpon destructans is one of the most devastating diseases of Panax notoginseng, and Trichoderma species are potential agents for the biocontrol of fungal diseases. Thus, we screened a total of 10 Trichoderma isolates against C. destructans and selected Trichoderma atroviride T2 as an antagonistic strain for further research. 6-Pentyl-2H-pyran-2-one (6PP) was identified as an important active metabolite in the fermentation broth of the strain and exhibited antifungal activity against C. destructans. Transcriptome and metabolome analyses showed that 6PP significantly disturbed the metabolic homeostasis of C. destructans, particularly the metabolism of amino acids. By constructing a gene coexpression network, ECHS1 was identified as the hub gene correlated with 6PP stress. 6PP significantly downregulated the expression of ECHS1 at the transcriptional level and combined with the ECHS1 protein. Autophagy occurred in C. destructans cells under 6PP stress. In conclusion, 6PP may induce autophagy in C. destructans by downregulating ECHS1 at the transcriptional level and inhibiting ECHS1 protein activity. 6PP is a potential candidate for the development of new fungicides against C. destructans.


Assuntos
Fungicidas Industriais/farmacologia , Hypocreales , Trichoderma/genética , Pironas/farmacologia
19.
Biosens Bioelectron ; 168: 112493, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32889394

RESUMO

Enzymatic biofuel cell (EBFC)-based self-powered biochemical sensors obviate the need for external power sources thus enabling device miniaturization. While recent efforts driven by experimentalists illustrate the potential of EBFC-based sensors for real-time monitoring of physiologically relevant biochemicals, a robust mathematical model that quantifies the contributions of sensor components and empowers experimentalists to predict sensor performance is missing. In this paper, we provide an elegant yet simple equivalent circuit model that captures the complex, three-dimensional interplay among coupled catalytic redox reactions occurring in an EBFC-based sensor and predicts its output signal with high correlations to experimental observations. The model explains the trade-off among chemical design parameters such as the surface density of enzymes, various reaction constants as well as electrical parameters in the Butler-Volmer relationship. The model shows that the linear dynamic range and sensitivity of the EBFC-based sensor can be independently fine-tuned by changing the surface density of enzymes and electron mediators at the anode and by enhancing reductant concentrations at the cathode. The mathematical model derived in this work can be easily adapted to understand a wide range of two-electrode systems, including sensors, fuel cells, and energy storage devices.

20.
J Cell Mol Med ; 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-32954649

RESUMO

A disintegrin and metalloproteinase 8 (ADAM8) protein is a multi-domain transmembrane glycoprotein which involves in extracellular matrix remodelling, cell adhesion, invasion and migration. ADAM8 and epithelial-mesenchymal transition (EMT) play an important role in tumour invasion has been well established. However, the interaction between ADAM8 and EMT has remained unclear. The data of colon cancer patients obtained from TCGA (The Cancer Genome Atlas) and GTEx (Genotype-Tissue Expression Project) were analysed by the bioinformatics research method. The expression of ADAM8 in colon cancer cells was up-regulated and down-regulated by transfecting with the expression plasmid and small interfering RNA, respectively. Transwell invasion assay, immunohistochemistry, immunocytochemistry, Western blotting and qRT-PCR were utilized to study the effect of ADAM8 on colon cancer cell's EMT and its related mechanisms. Analysis of TCGA and GTEx data revealed that ADAM8 was linked to poor overall survival in colon cancer patients. Besides, ADAM8 was correlated with multiple EMT biomarkers (E-cadherin, N-cadherin, Vimentin, Snail2 and ZEB2). In vitro, we also proved that the up-regulation of ADAM8 could promote EMT effect and enhance the invasive ability of colon cancer cells. On the contrary, the down-regulation of ADAM8 in colon cancer cells attenuated these effects above. Further studies suggested that ADAM8 modulated EMT on colon cancer cells through TGF-ß/Smad2/3 signalling pathway. Our research suggested that ADAM8 could be a potential biomarker for the prognosis of colon cancer and induced EMT to promote the invasion of colon cancer cells via activating TGF-ß/Smad2/3 signalling pathway.

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