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1.
Heart Surg Forum ; 23(2): E234-E238, 2020 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-32364921

RESUMO

OBJECTIVE: To study the effects of Yixintai pills on myocardial cell apoptosis in rats with adriamycin (ADR)-induced heart failure (HF) and the mechanism of action. METHODS: Sixty healthy male Wistar rats randomly were divided into Control, Model, Captopril, and Yixintai pill groups. A rat model of ADR-induced HF was constructed by intraperitoneal injection of ADR (2.5 mg/kg). The control group was given an equal volume of normal saline; the Yixintai pill and Captopril groups were given corresponding mediations (5 mg/kg) by lavage. After 4 weeks of treatment, fasting blood was collected to detect the contents of plasma rennin activity (PRA), angiotensin II (AngII), and aldosterone (ALD). B ultrasound was used to detect the heart structure, and the heart weight/body weight (HW/BW) ratio was calculated. The pathology of myocardial tissues was observed by HE staining. The apoptosis of myocardial cells was detected by TUNEL assay. The expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in serum were analyzed by ELISA, and the protein expression levels of protein kinase B (Akt), phosphorylated (p)-Akt, glycogen synthase kinase-3ß (GSK-3ß) and p-GSK-3ß in myocardial tissues were measured by Western blotting. RESULTS: Compared with the Control group, the PRA, AngII, ALD, left ventricular posterior wall thickness at end-systole (LVPWs), left ventricular posterior wall thickness at end-diastole (LVPWd), interventricular septal thickness at end-systole (IVSs), interventricular septal thickness at end-diastole (IVSd), HW/BW, TNF-α and IL-6 of model group increased significantly (P < .05). PRA, AngII, ALD, LVPWs, LVPWd, IVSs, IVSd, HW/BW, TNF-α and IL-6 of the Yixintai pill and Captopril groups were significantly lower than those of the Model group (P < .05). There were no significant differences in the indices between the Yixintai pill and Captopril groups (P > .05). In the Model group, lamellar necrosis, vacuolar degeneration, increased myocardial fibers and lamellar dissolution of myocardial cells were found in myocardial tissues. However, the myocardial cells of the Control group were neatly arranged and clearly structured, and only a few ones underwent fibrosis. There were mild myocardial fibrosis and vacuolar degeneration in the Yixintai pill and Captopril groups, and the degeneration and hyperplasia of myocardial fibers were obviously relieved. Compared with the Control group, the apoptosis index (AI) of the Model group increased significantly (P < .05). The AI values of the Yixintai pill and Captopril groups were significantly lower than those of the Model group (P < .05). Compared with the Control group, the expression levels of p-Akt and p-GSK-3ß in the Model group decreased significantly (P < .05). The expression levels of p-Akt and p-GSK-3ß in the Yixintai pill and Captopril groups were significantly higher than those of the Model group (P < .05), whereas the former 2 groups had similar results (P > 0.05). CONCLUSION: Yixintai pills may inhibit myocardial cell apoptosis and ventricular remodeling in rats by up-regulating PI3K/Akt/GSK-3ß signal, thus protecting the heart function.

2.
Nat Commun ; 11(1): 1146, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32123171

RESUMO

Linear ubiquitination is a critical regulator of inflammatory signaling pathways. However, linearly ubiquitinated substrates and the biological significance of linear ubiquitination is incompletely understood. Here, we show that STAT1 has linear ubiquitination at Lys511 and Lys652 residues in intact cells, which inhibits STAT1 binding to the type-I interferon receptor IFNAR2, thereby restricting STAT1 activation and resulting in type-I interferon signaling homeostasis. Linear ubiquitination of STAT1 is removed rapidly by OTULIN upon type-I interferon stimulation, which facilitates activation of interferon-STAT1 signaling. Furthermore, viruses induce HOIP expression through the NF-κB pathway, which in turn increases linear ubiquitination of STAT1 and thereby inhibits interferon antiviral response. Consequently, HOIL-1L heterozygous mice have active STAT1 signaling and enhanced responses to type-I interferons. These findings demonstrate a linear ubiquitination-mediated switch between homeostasis and activation of type-I interferon signaling, and suggest potential strategies for clinical antiviral therapy.

3.
Biomater Sci ; 8(8): 2255-2263, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32129378

RESUMO

Cell-penetrating peptides (CPPs) have been considered as a powerful tool to improve the intracellular and nuclear delivery efficiency of nanocarriers. However, their clinical application is limited because of their nonspecific targeting function, short half-life, and severe system toxicity. Herein, we have developed a polymeric nanocarrier with a tumor acidity-activatable arginine-rich (R9) peptide for targeted drug delivery. The nanocarrier is fabricated with a R9-conjugated amphiphilic diblock polymer of poly(ethylene glycol) (PEG) and poly(hexyl ethylene phosphate) (PHEP), and then further coated with tumor acidity-activatable polyanionic polyphosphoester through electrostatic interaction in order to block the nonspecific targeting function of the R9 peptide. In the slightly acidic tumor extracellular environment (∼pH 6.5), tumor acidity-activatable polyanionic polyphosphoester would be deshielded from the nanoparticles, resulting in the re-exposure of the R9 peptide to enhance tumor cellular uptake. As a result, intracellular concentration of payload in 4T1 tumor cells significantly increased at pH 6.5. And, we further demonstrate that such a delivery system remarkably promoted the anti-tumor efficiency of chemotherapeutic drugs in tumor-bearing mice, offering great potential for drug delivery and cancer therapy.

4.
Biol Pharm Bull ; 43(3): 533-539, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32115512

RESUMO

Renal interstitial fibrosis (RIF) is a common pathological characteristic associated with end-stage renal disease. However, treatment strategies for RIF are still very limited. In this study, we reported that kaempferol, a classic flavonoid, exhibited strong and widely inhibitory effect on the expression of fibrosis related genes in transforming growth factor beta 1 (TGF-ß1) treated NRK-52E cells. Further studies revealed that kaempferol inhibited TGF-ß1 induced epithelial-mesenchymal transition (EMT) process of NRK-52E cells and improved renal function deterioration and RIF in unilateral ureteral obstruction (UUO) rats. After exploring the underlying mechanisms, we found that kaempferol was able to activate the BMP-7-Smad1/5 pathway, rather than the TGF-ß1-Smad2/3 pathway. To further validate these results, DMH1 and BMP-7 knockdown were utilized at the cellular level and the results showed that both methods were able to antagonize the effects of kaempferol on the EMT process of NRK-52E cells induced by TGF-ß1. In UUO rats, inhibition of BMP-7 signaling by DMH1 also reversed the effects of kaempferol on renal function decline and RIF. Taken together, our findings demonstrated that kaempferol could be a good candidate for renal fibrosis treatment.

5.
BMC Pulm Med ; 20(1): 68, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32197604

RESUMO

BACKGROUND: Chronic cough has an important impact on physical, social and psychological aspects. A simple and effective method to assess different aspects of chronic cough severity is required. We aimed to develop a simple, self-completed test, Cough Evaluation Test (CET), to evaluate cough severity and its impact on health. METHOD: The items of preliminary CET were generated based on literature review and clinical practice. Items reduction was conducted by modified Delphi method. Patients with chronic cough were recruited to complete CET, Cough Visual Analog Scales (VAS), Mandarin Chinese version of the Leicester Cough Questionnaire (LCQ-MC), and Cough Symptom Score (CSS). Reassessments were performed at 1 week apart before treatment, and after more than 2 weeks treatments. Concurrent validation, internal consistency, repeatability, responsiveness and the minimal important difference (MID) were determined. RESULTS: CET consists of five items with a 5-point Likert scale (1-5 scaling of items, 5-25 score range). The Cronbach's alpha values for CET was 0.80. CET showed a stronger correlation with LCQ-MC (r = - 0.74) compared to that between LCQ-MC with VAS (r = - 0.61). CET also showed a stronger correlation with VAS (r = 0.70) compared to that between VAS with other measures. Intraclass correlation coefficients for CET was 0.84. In patients undergoing treatment, CET scores significantly changed (p < 0.0001). The MID of CET was 2. CONCLUSION: Cough Evaluate Test is a reliable, valid and responsive tool to simply evaluate impact of cough on physical, social and psychological aspects.

6.
Addiction ; 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31943486

RESUMO

BACKGROUND AND AIMS: The focus of this paper is on the improvement of substance use disorder (SUD) screening and measurement. Using a multi-dimensional item response theory model, the bifactor model, we provide a psychometric harmonization between SUD, depression, anxiety, trauma, social isolation, functional impairment and risk-taking behavior symptom domains, providing a more balanced view of SUD. The aims are to (1) develop the item-bank, (2) calibrate the item-bank using a bifactor model that includes a primary dimension and symptom-specific subdomains, (3) administer using computerized adaptive testing (CAT) and (4) validate the CAT-SUD in Spanish and English in the United States and Spain. DESIGN: Item bank construction, item calibration phase, CAT-SUD validation phase. SETTING: Primary care, community clinics, emergency departments and patient-to-patient referrals in Spain (Barcelona and Madrid) and the United States (Boston and Los Angeles). PARTICIPANTS/CASES: Calibration phase: the CAT-SUD was developed via simulation from complete item responses in 513 participants. Validation phase: 297 participants received the Composite International Diagnostic Interview (CIDI) and the CAT-SUD. MEASUREMENTS: A total of 252 items from five subdomains: (1) SUD, (2) psychological disorders, (3) risky behavior, (4) functional impairment and (5) social support. CAT-SUD scale scores and CIDI SUD diagnosis. FINDINGS: Calibration: the bifactor model provided excellent fit to the multi-dimensional item bank; 168 items had high loadings (> 0.4 with the majority > 0.6) on the primary SUD dimension. Using an average of 11 items (four to 26), which represents a 94% reduction in respondent burden (average administration time of approximately 2 minutes), we found a correlation of 0.91 with the 168-item scale (precision of 5 points on a 100-point scale). VALIDATION: strong agreement was found between the primary CAT-SUD dimension estimate and the results of a structured clinical interview. There was a 20-fold increase in the likelihood of a CIDI SUD diagnosis across the range of the CAT-SUD (AUC = 0.85). CONCLUSIONS: We have developed a new approach for the screening and measurement of SUD and related severity based on multi-dimensional item response theory. The bifactor model harmonized information from mental health, trauma, social support and traditional SUD items to provide a more complete characterization of SUD. The CAT-SUD is highly predictive of a current SUD diagnosis based on a structured clinical interview, and may be predictive of the development of SUD in the future.

7.
PLoS Pathog ; 16(1): e1008215, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31899788

RESUMO

CREB-binding protein (CBP) participates in numerous transcription events. However, cell-intrinsic inhibitors of CBP are poorly defined. Here, we found that cellular USP12 interacts with the HAT domain of CBP and inhibits CBP's acetyltransferase activity. Interestingly, USP12 positively regulates interferon (IFN) antiviral signaling independently of its deubiquitinase activity. Furthermore, we found that in IFN signaling USP12 translocates from the cytoplasm to the nucleus. The decrease in cytoplasmic USP12 facilitates CBP-induced acetylation and activation of IFN signaling proteins in the cytoplasm. Moreover, USP12 accumulation in the nucleus blocks CBP-induced acetylation of phosphorylated STAT1 (p-STAT1) and therefore inhibits the dephosphorylation effects of TCPTP on p-STAT1, which finally maintains nuclear p-STAT1 levels and IFN antiviral efficacy. USP12 nuclear translocation extends our understanding of the regulation of the strength of IFN antiviral signaling. Our study uncovers a cell-intrinsic regulation of CBP acetyltransferase activity and may provide potential strategies for IFN-based antiviral therapy.


Assuntos
Proteína de Ligação a CREB/antagonistas & inibidores , Interferons/fisiologia , Ubiquitina Tiolesterase/metabolismo , Acetilação , Animais , Antivirais/metabolismo , Proteína de Ligação a CREB/metabolismo , Citoplasma/metabolismo , Inibidores Enzimáticos/metabolismo , Células HCT116 , Células HEK293 , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Domínios Proteicos , Células RAW 264.7 , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais
8.
Appl Biochem Biotechnol ; 190(2): 529-539, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31396885

RESUMO

Because elevated levels of caffeine intake can cause many health complications, it is necessary to develop an accurate, simple, rapid, and cost-effective methodology to quantify caffeine in commonly consumed products. This article discusses electrochemical methods to synthesize platinum-graphene hybrid nanosheets (Pt-GR), and how these methods can be utilized to create a new modified electrode, the platinum-graphene nanohybrid glass carbon electrode (Pt-GR/GCE). The electrochemical behavior of caffeine on Pt-GR/GCE was studied by differential pulse voltammetry (DPV). The results showed that a sensitive oxidation peak was observed at 1.336 V in 0.01 mol L-1 H2SO4 buffer solution, indicating that the Pt-GR/GCE exhibited a good electrooxidation activity towards caffeine. The detection limit is 1.129 × 10-7 mol L-1. The modified electrode was applied to the determination of caffeine in real samples with satisfactory electrocatalytic results.

9.
Mol Cell ; 77(4): 734-747.e7, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31812350

RESUMO

Mutation and prevalence of pathogenic viruses prompt the development of broad-spectrum antiviral strategies. Viperin is a potent antiviral protein that inhibits a broad range of viruses. Unexpectedly, we found that Viperin protein production in epithelium is defective in response to both viruses and interferons (IFNs). We further revealed that viruses and IFNs stimulate expression of the acetyltransferase HAT1, which induces Lys197-acetylation on Viperin. Viperin acetylation in turn recruits UBE4A that stimulates K6-linked polyubiquitination at Lys206 of Viperin, leading to Viperin protein degradation. Importantly, UBE4A deficiency restores Viperin protein production in epithelium. We then designed interfering peptides (IPs) to inhibit UBE4A binding with Viperin. We found that VIP-IP3 rescues Viperin protein production in epithelium and therefore enhances cellular antiviral activity. VIP-IP3 renders mice more resistant to viral infection. These findings could provide strategies for both enhancing host broad-spectrum antiviral response and improving the efficacy of IFN-based antiviral therapy.

10.
Ann Transl Med ; 7(20): 586, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31807567

RESUMO

Background: Acute variceal bleeding is one of the critical complications in patients with liver cirrhosis. Severe renal vasoconstriction in consequence of low peripheral vascular resistance triggers the reduction of glomerular filtration rate (GFR), and thus induces acute kidney injury (AKI)/hepato-renal syndrome (HRS). Terlipressin and octreotide have been used in the management of cirrhotic patients with variceal bleeding. Also, terlipressin has been recommended as the international first-line pharmacological therapy for the treatment of HRS. In addition, the use of renal functional magnetic resonance imaging (fMRI) has become increasingly prevalent in research and clinical applications. However, the renal function-protective effect of terlipressin and octreotide and the value of fMRI in monitoring renal function remains unclear in patients with cirrhosis undergoing acute variceal bleeding. Methods: This is a multicenter, randomized controlled trial (RCT). Participants will be 1:1 assigned randomly into either terlipressin or octreotide groups. Sixty participants with clinically and/or pathologically diagnosed cirrhosis and active gastroesophageal variceal bleeding (GVB) will be recruited in several sites in China. Participants will receive either the treatment of terlipressin or octreotide after assigned into each group. The primary end point for the trial is the renal function. The secondary end points are (I) renal perfusion; (II) renal blood oxygenation; (III) failure to control bleeding; (IV) intra-hospital rebleeding; (V) intra-hospital mortality; (VI) adverse events (AE); (VII) overall survival. Statistical analysis including multivariate Cox regression, Kaplan-Meier analysis with log-rank test, etc. will be conducted. Discussion: The study will provide new insight into the protection of renal function in the process of the treatment of variceal bleeding in patients with cirrhosis. Trial registration number: NCT04028323.

11.
Med Sci Monit ; 25: 7182-7190, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31550244

RESUMO

BACKGROUND The role of bone marrow-derived mesenchymal stem cells (BM-MSCs) in liver fibrosis remains poorly understood. This study aimed to use a mouse model of carbon tetrachloride (CCL4)-induced liver fibrosis to investigate the effects of BM-MSCs during liver hypoxia and the involvement of the transforming growth factor beta 1 (TGF-ß1) and SMADs pathway. MATERIAL AND METHODS Thirty C57BL/6 mice were randomly divided into the control group (n=10), the model group (n=10), and the BM-MSC-treated model group (n=10). In the model group, liver fibrosis was induced by intraperitoneal injection of CCl4. BM-MSCs were transplanted after 12 weeks of CCl4 treatment. The serum biochemical parameters and histological changes in the liver, using histochemical stains, were investigated. The expression of collagen type I (collagen I), alpha-smooth muscle actin (alpha-SMA), TGF-ß1, SMAD3, SMAD7, hypoxia-inducible factor 1 alpha (HIF-1alpha), and vascular endothelial grow factor (VEGF) were assessed by immunohistochemistry and quantitative real-time polymerase chain (RT-qPCR) reaction. RESULTS Treatment with BM-MSCs reduced the expression of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared with the model group, and reduced liver fibrosis determined histologically using hematoxylin and eosin (H&E) and Masson's trichrome staining compared with the model group. The area of liver fibrosis decreased after BM-MSCs treatment (p<0.05). Protein expression of HIF-1alpha and VEGF were decreased after BM-MSCs treatment (p<0.05). Transplantation of BM-MSCs reduced the mRNA expression of TGF-ß1, collagen I, alpha-SMA, and SMAD3 (p<0.05). CONCLUSIONS BM-MSC transplantation reduced CCl4-induced murine liver fibrosis, indicating that in a hypoxic microenvironment, BM-MSCs may inhibit the TGFß-1/SMADs pathway.


Assuntos
Fibrose/metabolismo , Cirrose Hepática/terapia , Células-Tronco Mesenquimais/fisiologia , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Medula Óssea/metabolismo , Tetracloreto de Carbono/farmacologia , Hipóxia Celular/fisiologia , China , Modelos Animais de Doenças , Fibrose/fisiopatologia , Hipóxia/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Smad/metabolismo , Proteínas Smad/fisiologia , Fator de Crescimento Transformador beta/metabolismo
12.
Allergy Asthma Immunol Res ; 11(6): 871-884, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31552721

RESUMO

PURPOSE: An older female predominance has been reported among chronic cough patients in Western countries, which is considered to be associated with a higher cough sensitivity in females. However, the characteristics of Chinese chronic cough patients remain unclear. This study aimed to explore the age and sex distribution as well as their relationship with cough reflex sensitivity to capsaicin in Chinese chronic cough patients. METHODS: We analyzed the demographic features of 1,882 consecutive chronic cough patients who attended our cough clinic in Guangzhou, China. Cough sensitivity to capsaicin, which was defined as the lowest concentration of capsaicin causing 5 coughs or more (C5), was measured in 539 of the 1,882 patients and 68 healthy volunteers. RESULTS: The mean age of the patients was 43.0 ± 13.7 years and patients aged <50 years accounted for more than two-thirds of the study population. Around 87% of the patients were never-smokers. The proportion of females (51.5%) was almost equal to that of males (48.5%). The pattern of the age and sex distribution was consistently reflected within most common causes of chronic cough, while a female predominance was shown in patients with cough-variant asthma and patients aged ≥50 years. Female patients had higher cough sensitivity to capsaicin than male patients (log C5: 1.58 ± 0.84 vs. 2.04 ± 0.84 µmol/L, P = 0.001), and patients aged ≥50 years had higher cough sensitivity to capsaicin than patients aged <50 years. CONCLUSIONS: In China, patients with chronic cough have a roughly equal sex distribution and a middle-aged predominance, irrespective of a higher cough sensitivity to capsaicin in females and older patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02591550.

13.
Colloids Surf B Biointerfaces ; 184: 110433, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31522024

RESUMO

Surface fabrication is an effective method for functional materials development. This work investigated the use of cellulose-binding domain (CBD) fused detergent lipase for fabrication of easy-cleaning surfaces. As a result, the CBD conjugated Lipase-A (LipA-CBD) demonstrated a multi-layer self-assemble on cotton fabric surface and enhanced hydrophobicity as detected by both scanning electron microscope and water contact angle measurement. Compared to the normal cotton surfaces, such self-assembly bioactive surfaces afforded effective easy-cleaning functionality against both water and lipids based stains with the most significant stain removing ratio as examined through the simulated laundering test. Additionally, this surface assembled LipA-CBD presented good thermal stability with 15 days of half-life detected for 70°C and over 60 days for room temperature. Although there is a gradual decrease in sun irradiation stability and laundering durability, the functionality could be quickly recovered by re-applying the LipA-CBD as the self-assembly coating in the rinsing process. These results presented a green, simple and timesaving method to develop new easy-cleaning cotton fabrics via interfacial self-assembly of biomacromolecules.

14.
J Org Chem ; 84(14): 9161-9168, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31262173

RESUMO

A ligand-promoted palladium(II)-catalyzed synthesis of arylalkynes and phthalides from benzoic acids and bromoalkynes via carboxylate-assisted ortho-C-H activation is reported. A series of phthalides with various functional groups are prepared via ortho-alkynylation and alkynylation-annulation. Moreover, the key ortho-alkynylated products are also obtained by controlling the reaction conditions. In addition, heteroaryl acids could react smoothly to form the corresponding alkynylation and cyclization products.

15.
Environ Sci Pollut Res Int ; 26(24): 24988-24997, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31240663

RESUMO

Essential oils (EOs) extracted from leaves (EL) and fruit pericarp (EFP) of Zanthoxylum planispinum var. dintanensis were analyzed for their chemical composition by GC-MS technique and evaluated for their fumigant, contact toxicity and repellency against three stored-product insects, namely Tribolium castaneum, Lasioderma serricorne, and Liposcelis bostrychophila adults. Results of GC-MS analysis manifested that EL and EFP of Z. planispinum var. dintanensis were mainly composed of oxygenated monoterpenes. Major components included linalool, sylvestrene and terpinen-4-ol. The obvious variation observed between two oil samples was that EL contained 2-dodecanone (11.52%) in addition to the above mentioned components, while this constituent was not detected in EFP. Bioassays of insecticidal and repellent activities were performed for EL, EFP as well as some of their individual compounds (linalool, terpinen-4-ol and 2-dodecanone). Testing results indicated that EL, EFP, linalool, terpinen-4-ol and 2-dodecanone exhibited potent insecticidal and repellent activities against the three target insects selected. Among the three individual compounds, 2-dodecanone was significantly toxic to T. castaneum (LD50 = 5.21 µg/adult), L. serricorne (LD50 = 2.54 µg/adult) and L. bostrychophila (LD50 = 23.41 µg/cm2) in contact assays and had beneficial repellent effects on L. serricorne at 2 and 4 h post-exposure. The anti-insect efficacy of Z. planispinum var. dintanensis EO suggests it has potential to be used as botanical insecticide or repellent to control pest damage in warehouses and grain stores.


Assuntos
Repelentes de Insetos/farmacologia , Inseticidas/análise , Monoterpenos/química , Óleos Voláteis/química , Terpenos/química , Zanthoxylum/química , Animais , Besouros/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Repelentes de Insetos/química , Inseticidas/química , Dose Letal Mediana , Monoterpenos/análise , Oxirredução , Tribolium/química
16.
J Colloid Interface Sci ; 552: 179-185, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31125828

RESUMO

In this study, ultrathin two-dimensional (2D) bismuth tungstate (Bi2WO6) nanosheets were adopted as a Pt support for photo-assisted electrocatalytic methanol oxidation. Compared with traditional electrocatalytic reactions, the photo-assisted electrocatalytic methanol oxidation reactions of Pt-2D Bi2WO6 nanosheets under simulated solar light and visible light irradiation were improved 5.1 and 2.0 times, respectively. The better photo-assisted electrocatalytic methanol oxidation activities of Pt-Bi2WO6 nanosheets can be attributed to the unique 2D structure that strengthens the oxidation ability of photogenerated holes, reduces the time required for carrier migration, reduces the recombination rate of carriers and provides a larger specific surface area. Additionally, our experimental results reveal the critical factors of photo-assisted enhanced electrocatalytic activities for methanol oxidation and provide a new way to improve the photo-assisted electrocatalytic activities for methanol oxidation.

17.
BMC Plant Biol ; 19(1): 193, 2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31072347

RESUMO

BACKGROUND: Wheat production is largely restricted by adverse environmental stresses. Under many undesirable conditions, endoplasmic reticulum (ER) stress can be induced. However, the physiological and molecular responses of wheat to ER stress remain poorly understood. We used dithiothreitol (DTT) and tauroursodeoxycholic acid (TUDCA) to induce or suppress ER stress in wheat cells, respectively, with the aim to reveal the molecular background of ER stress responses using a combined approach of transcriptional profiling and morpho-physiological characterization. METHODS: To understand the mechanism of wheat response to ER stress, three wheat cultivars were used in our pre-experiments. Among them, the cultivar with a moderate stress tolerance, Yunong211 was used in the following experiments. We used DTT (7.5 mM) to induce ER stress and TUDCA (25 µg·mL- 1) to suppress the stress. Under three treatment groups (Control, DTT and DTT + TUDCA), we firstly monitored the morphological, physiological and cytological changes of wheat seedlings. Then we collected leaf samples from each group for RNA extraction, library construction and RNA sequencing on an Illumina Hiseq platform. The sequencing data was then validated by qRT-PCR. RESULTS: Morpho-physiological results showed DTT significantly reduced plant height and biomass, decreased contents of chlorophyll and water, increased electrolyte leakage rate and antioxidant enzymes activity, and accelerated the cell death ratio, whereas these changes were all remarkably alleviated after TUDCA co-treatment. Therefore, RNA sequencing was performed to determine the genes involved in regulating wheat response to stress. Transcriptomic analysis revealed that 8204 genes were differentially expressed in three treatment groups. Among these genes, 158 photosynthesis-related genes, 42 antioxidant enzyme genes, 318 plant hormone-related genes and 457 transcription factors (TFs) may play vital roles in regulating wheat response to ER stress. Based on the comprehensive analysis, we propose a hypothetical model to elucidate possible mechanisms of how plants adapt to environmental stresses. CONCLUSIONS: We identified several important genes that may play vital roles in wheat responding to ER stress. This work should lay the foundations of future studies in plant response to environmental stresses.


Assuntos
Estresse do Retículo Endoplasmático/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Transcriptoma/genética , Triticum/genética , Triticum/fisiologia , Ditiotreitol/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Ontologia Genética , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/genética , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Reprodutibilidade dos Testes , Análise de Sequência de RNA , Ácido Tauroquenodesoxicólico/farmacologia , Fatores de Transcrição/metabolismo , Transcriptoma/efeitos dos fármacos , Triticum/anatomia & histologia
18.
Nat Microbiol ; 4(11): 1872-1884, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30988430

RESUMO

Outbreaks of viral infections are a global health burden. Although type I interferon (IFN-I) exerts broad-spectrum antiviral effects, its antiviral efficacy in host cells is largely restricted by viruses. How the antiviral efficacy of IFN-I can be improved remains to be explored. Here, we identified the ADP-ribosyltransferase poly(ADP-ribose) polymerase family member 11 (PARP11) as a potent regulator of IFN-I antiviral efficacy. PARP11 does not restrict IFN-I production induced by vesicular stomatitis virus or Sendai virus but inhibits the strength of IFN-I-activated signalling. Mechanistically, PARP11 mono-ADP-ribosylates the ubiquitin E3 ligase ß-transducin repeat-containing protein (ß-TrCP). Mono-ADP-ribosylation of ß-TrCP promotes IFNα/ß receptor subunit 1 (IFNAR1) ubiquitination and degradation. Moreover, PARP11 expression is upregulated by virus infections, including vesicular stomatitis virus, herpes simplex virus-1 and influenza A virus, thus promoting ADP-ribosylation-mediated viral evasion. We further highlight the potential for repurposing clinical ADP-ribosylation inhibitors. We found that rucaparib can target PARP11 to stabilize IFNAR1 and therefore exhibits efficient enhancement of IFN-I signalling and the host antiviral response. Consequently, rucaparib renders mice more resistant to viral infection. Our study updates the understanding of how ß-TrCP regulates its substrates and may provide a druggable target for improving IFN antiviral efficacy.


Assuntos
Interferon Tipo I/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Receptor de Interferon alfa e beta/química , Receptor de Interferon alfa e beta/metabolismo , Viroses/imunologia , Proteínas Contendo Repetições de beta-Transducina/metabolismo , ADP-Ribosilação , Animais , Células Cultivadas , Modelos Animais de Doenças , Células HEK293 , Células Hep G2 , Humanos , Indóis/administração & dosagem , Indóis/farmacologia , Camundongos , Proteólise , Vírus Sendai/imunologia , Transdução de Sinais , Ubiquitinação , Células Vero , Vesiculovirus/imunologia , Viroses/tratamento farmacológico , Viroses/metabolismo
20.
Cell Death Differ ; 26(10): 1929-1941, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30644439

RESUMO

Necroptosis is a programmed form of necrotic cell death, which is tightly regulated by the necroptotic signaling pathway containing receptor-interacting protein (RIP)1, RIP3, and mixed-lineage kinase domain-like (MLKL) protein. In addition to the RIP1-RIP3-MLKL axis, other factors regulating necroptosis are still largely unknown. Here a cell-based small-molecule screening led to the finding that BET inhibitors protected cells from necroptosis in the TNFα/Smac-mimetic/Z-VAD-FMK (TSZ)-induced cell necroptosis model. Mechanistic studies revealed that BET inhibitors acted by downregulating MLKL expression. Further research demonstrated that BRD4, IRF1, P-TEFb, and RNA polymerase II formed a transcription complex to regulate the expression of MLKL, and BET inhibitors interfered with the transcription complex formation. In necroptosis-related disease model, the BET inhibitor JQ-1 showed promising therapeutic effects. Collectively, our studies establish, for the first time, BRD4 as a new epigenetic factor regulating necroptosis, and highlight the potential of BET inhibitors in the treatment of necroptosis-related diseases.

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