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1.
Am J Cardiol ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33159905

RESUMO

We aimed to explore the utility of multiple biomarkers with GRACE risk stratification for non-ST-elevation myocardial infarction (NSTEMI). A total of 1,357 patients diagnosed with NSTEMI were enrolled in this study at multiple medical centers in Tianjin, China. The outcomes were 1-year all-cause death and major adverse cardiac events (MACE: all-cause death, hospital admission for unstable angina, hospital admission for heart failure, nonfatal recurrent myocardial infarction, and stroke). C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were calculated to verify that the biomarkers improve the predictive accuracy of the GRACE score. A total of 57 participants died, while 211 participants experienced 231 MACEs during follow-up (mean: 339 days). For all-cause death, the combination of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and D-dimer improved the predictive accuracy of GRACE the most, with C-index, IDI, and NRI values of 0.88, 0.085, and 1.223, respectively. For MACE, trigeminal combination of NT-proBNP, fibrinogen, and D-dimer resulted in C-index, IDI, and NRI values of 0.80, 0.079, and 0.647, respectively. As a result, NT-proBNP, D-dimer, fibrinogen, and GRACE comprise a new scoring system for assessing 1-year clinical events. Kaplan-Meier analysis revealed a significant increase in 1-year mortality (score ≥3.85 vs <3.85, p < 0.0001) and 1-year MACE (score ≥1.72 vs <1.72, p < 0.0001) between different score groups. In conclusion, the combination of NT-proBNP and D-dimer added prognostic value to GRACE for all-cause death. Combining NT-proBNP, fibrinogen, and D-dimer increased the prognostic value of GRACE for MACE. This newly developed scoring system is strongly correlated with all-cause mortality and MACE, and can be easily utilized in clinical practice.

2.
Cell Commun Signal ; 18(1): 175, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33148274

RESUMO

The regulation of the translation of messenger RNA (mRNA) in eukaryotic cells is critical for gene expression, and occurs principally at the initiation phase which is mainly regulated by eukaryotic initiation factors (eIFs). eIFs are fundamental for the translation of mRNA and as such act as the primary targets of several signaling pathways to regulate gene expression. Mis-regulated mRNA expression is a common feature of tumorigenesis and the abnormal activity of eIF complexes triggered by upstream signaling pathways is detected in many tumors, leading to the selective translation of mRNA encoding proteins involved in tumorigenesis, metastasis, or resistance to anti-cancer drugs, and making eIFs a promising therapeutic target for various types of cancers. Here, we briefly outline our current understanding of the biology of eIFs, mainly focusing on the effects of several signaling pathways upon their functions and discuss their contributions to the initiation and progression of tumor growth. An overview of the progress in developing agents targeting the components of translation machinery for cancer treatment is also provided. Video abstract.

3.
J Speech Lang Hear Res ; : 1-12, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33151817

RESUMO

Purpose The aim of this study is to investigate whether human auditory frequency tuning can be influenced by tonal language experience. Method Perceptual tuning measured via psychophysical tuning curves and cochlear tuning derived via stimulus-frequency otoacoustic emission suppression tuning curves in 14 native speakers of a tonal language (Mandarin) were compared to those of 14 native speakers of a nontonal language (English) at 1 and 4 kHz. Results Group comparisons of both psychophysical tuning curves (p = .046) and stimulus-frequency otoacoustic emission suppression tuning curves (p = .007) in the 4-kHz region indicated sharper frequency tuning in the Mandarin-speaking group relative to the English-speaking group. The auditory tuning was better at the higher (4 kHz) than the lower (1 kHz) probe frequencies (p < .001). Conclusions The sharper auditory tuning in the 4-kHz cochlear region is associated with long-term tonal language (i.e., Mandarin) experience. Experience-dependent plasticity of tonal language may occur before the sound signal reaches central neural stages, as peripheral as the cochlea.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33169982

RESUMO

Tumor-associated macrophages (TAMs), a major player in the tumor microenvironment, were recently recognized as a potential therapeutic target. To date, very few anticancer drugs or drug-delivery systems were designed to target the TAMs. Inspired by the "eat me" signal, phosphatidylserine (PS), mediated phagocytic clearance of apoptotic bodies, in this study, the matrix metalloproteinase 2 (MMP2)-sensitive PS-modified nanoparticles were developed. In the design, the PS is externalized to the nanoparticles' surface only when the nanoparticles reach the MMP2-overexpressing tumor site, allowing for the TAM-specific phagocytosis. The nanoparticles' excellent macrophage/TAM selectivity was observed in various biological models, including various cell lines, coculture cells, coculture cell spheroids, zebrafish, and tumor-bearing mice. The nanoparticles' TAM specificity remarkably enhanced the TAM depletion capability of the loaded model drug, dasatinib, resulting in the improved anticancer activity. The MMP2-sensitive apoptotic body-mimicking nanoparticles might be a promising delivery tool for TAM-centered cancer diagnoses and treatments.

5.
J Clin Nurs ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33141483

RESUMO

AIMS AND OBJECTIVES: To assess the level of stress response, self-efficacy and perceived social support status of working nurses during the outbreak of the COVID-19 and investigate potential factors affecting their stress. BACKGROUND: The stress level of clinical nurses directly affects their physical and mental health and work efficiency. DESIGN: This study was a cross-sectional investigation, which was performed following the STROBE checklist. The current study was conducted in February 2020 by selecting clinical nurses from the Zigong First People's Hospital for investigation. METHODS: At the peak of the COVID-19 outbreak in China, we assessed clinical nurses with the Stanford Acute Stress Reaction Questionnaire, the General Self-Efficacy Scale and the Perceived Social Support Scale. Specifically, the nurses were divided into three groups: (a) nurses supporting Wuhan; (b) nurses in the department of treating the COVID-19 patients in our hospital (epidemic department); and (c) nurses in the general department without the COVID-19 patients in our hospital (non-epidemic department). RESULTS: A total of 1092 clinical nurses were surveyed with 94 nurses in Wuhan, 130 nurses treating COVID-19 patients in our hospital and 868 nurses working without direct contact with diagnosed COVID-19 patients. The mean stress score of all surveyed nurses was 33.15 (SD: 25.551). There was a statistically significant difference in stress response scores between different departments. Noticeably, the nurses who went to support in Wuhan showed a weaker stress response than the nurses who stayed in our hospital (mean: 19.98 (Wuhan) vs. 32.70 (epidemic department in our hospital) vs. 34.64 (non-epidemic department in our hospital)). In addition, stress was negatively correlated with general self-efficacy and perceived social support. CONCLUSION: The present study suggested that the stress status of second-line nurse without direct contact with diagnosed COVID-19 patients was more severe than that of first-line nurses who had direct contact with COVID-19 patients. RELEVANCE TO CLINICAL PRACTICE: Our study indicated the importance of psychological status of second-line medical staff during the global pandemic.

6.
Front Immunol ; 11: 2015, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072069

RESUMO

Trichinella infection can induce macrophages into the alternatively activated phenotype, which is primarily associated with the development of a polarized Th2 immune response. In the present study, we examined the immunomodulatory effect of T. spiralis thioredoxin peroxidase-2 (TsTPX2), a protein derived from T. spiralis ES products, in the regulation of Th2 response through direct activation of macrophages. The location of TsTPX2 was detected by immunohistochemistry and immunofluorescence analyses. The immune response in vivo induced by rTsTPX2 was characterized by analyzing the Th2 cytokines and Th1 cytokines in the peripheral blood. The rTsTPX2-activated macrophages (MrTsTPX2) were tested for polarization, their ability to evoke naïve CD4+ T cells, and resistance to the larval infection after adoptive transfer in BALB/c mice. The immunolocalization analysis showed TsTPX2 in cuticles and stichosome of T. spiralis ML. The immunostaining was detected in cuticles and stichosome of T. spiralis Ad3 and ML, as well as in tissue-dwellings around ML after the intestines and muscle tissues of infected mice were incubated with anti-rTsTPX2 antibody. Immunization of BALB/c mice with rTsTPX2 could induce a Th1-suppressing mixed immune response given the increased levels of Th2 cytokines (IL-4 and IL-10) production along with the decreased levels of Th1 cytokines (IFN-γ, IL-12, and TNF-α). In vitro studies showed that rTsTPX2 could directly drive RAW264.7 and peritoneal macrophages to the M2 phenotype. Moreover, MrTsTPX2 could promote CD4+ T cells polarized into Th2 type in vitro. Adoptive transfer of MrTsTPX2 into mice suppressed Th1 responses by enhancing Th2 responses and exhibited a 44.7% reduction in adult worm burden following challenge with T. spiralis infective larval, suggesting that the TsTPX2 is a potential vaccine candidate against trichinosis. Our study showed that TsTPX2 would be at least one of the molecules to switch macrophages into the M2 phenotype during T. spiralis infection, which provides a new therapeutic approach to various inflammatory disorders like allergies or autoimmune diseases.

7.
Nat Commun ; 11(1): 4968, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009413

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread to become a worldwide emergency. Early identification of patients at risk of progression may facilitate more individually aligned treatment plans and optimized utilization of medical resource. Here we conducted a multicenter retrospective study involving patients with moderate COVID-19 pneumonia to investigate the utility of chest computed tomography (CT) and clinical characteristics to risk-stratify the patients. Our results show that CT severity score is associated with inflammatory levels and that older age, higher neutrophil-to-lymphocyte ratio (NLR), and CT severity score on admission are independent risk factors for short-term progression. The nomogram based on these risk factors shows good calibration and discrimination in the derivation and validation cohorts. These findings have implications for predicting the progression risk of COVID-19 pneumonia patients at the time of admission. CT examination may help risk-stratification and guide the timing of admission.


Assuntos
Infecções por Coronavirus/diagnóstico , Progressão da Doença , Pneumonia Viral/diagnóstico , Pneumonia , Tomografia Computadorizada por Raios X/métodos , Adulto , Betacoronavirus , China , Técnicas de Laboratório Clínico , Coinfecção , Infecções por Coronavirus/patologia , Infecções por Coronavirus/fisiopatologia , Feminino , Hospitalização , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/fisiopatologia , Análise de Regressão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
8.
ACS Nano ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33074660

RESUMO

Preparing transition-metal oxides in their two-dimensional (2D) form is the key to exploring their unrevealed low-dimensional properties, such as the p-type transparent superconductivity, topological Mott insulator state, existence of the condensed 2D electron/hole gas, and strain-tunable catalysis. However, existing approaches suffer from the specific constraint techniques and precursors that limit their product types. Here, we report a solution-based method to directly synthesize KNbO2 in 2D by an out-of-the-pot growth process at low temperature, which is observed directly in real time. The developed method can also be applied to other 2D ternary oxide syntheses, including CsNbO2 and composited NaxK1-xNbO2, and it can be extended to the preparation of self-assembled nanofilms. In addition, We demonstrate the emission of broadband photoluminescence (PL, λ ∼ 350-800 nm) from as-synthesized single-crystal 2D KNbO2 sheets down to a single unit cell thickness. The ultra-broadband emission is ascribed to the self-trapped excitation state (STEs) from the in-phase distortion of the NbO6 octahedrons in 2D NbO2- layers. Beyond the broader luminescent range and the robust material thermal stability of niobates, the absence of sample size restrictions and the large aspect ratio of the 2D oxide sheets will provide opportunities in miniaturizing and advancing 2D-materials integrated optoelectronic devices.

9.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 960-963, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018144

RESUMO

A good understanding of the origin of stimulus-frequency otoacoustic emission (SFOAE) fine structure in human ears and its probe level-dependency has potential clinical significance. In this study, we develop a two-component additive model, with total SFOAE unmixed into short- and long-latency components (or reflections) using time windowing method, to investigate the origin of SFOAE fine structure in humans from 40 to 70 dB SPL. The two-component additive model predicts that a spectral notch seen in the amplitude fine structure is produced when short- and long-latency components have opposite phases and comparable magnitudes. And the depth of spectral notch is significantly correlated with the amplitude difference between the two separated components, as well as their degree of opposite phase. Our independent evidence for components contributing to SFOAE fine structure suggests that amplitude, phase and delay fine structure in the human SFOAEs are a construct of the complex addition of two or more internal reflections with different phase slops in the cochlea.


Assuntos
Cóclea , Emissões Otoacústicas Espontâneas , Estimulação Acústica , Humanos
10.
Sci Rep ; 10(1): 17789, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33082412

RESUMO

B-box transcription factors (BBXs) are important regulators of flowering, photomorphogenesis, shade-avoidance, abiotic and biotic stresses and plant hormonal pathways. In Arabidopsis, 32 BBX proteins have been identified and classified into five groups based on their structural domains. Little is known about the fifth group members (BBX26-BBX32) and the detailed molecular mechanisms relevant to their functions. Here we identified B-box transcription factor 28 (BBX28) that interacts with Constans (CO), a transcriptional activator of Flowering Locus T (FT). Overexpressing BBX28 leads to late flowering with dramatically decreased FT transcription, and bbx28 deficient mutant displays a weak early flowering phenotype under long days (LD), indicating that BBX28 plays a negative and redundant role in flowering under LD. Additionally, the interaction between BBX28 and CO decreases the recruitment of CO to FT locus without affecting the transcriptional activation activity of CO. Moreover, the N-terminal cysteines, especially those within the B-box domain, are indispensable for the heterodimerization between BBX28 and CO and activation of CO on FT transcription. Genetic evidences show that the later flowering caused by BBX28 overexpression is compromised by CO ectopic expression. Collectively, these results supported that BBX28 functions with CO and FT to negatively regulate Arabidopsis flowering, in which the N-terminal conserved cysteines of BBX28 might play a central role.

11.
Nanotechnology ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33120370

RESUMO

Ag/TiO2 nanostructure arrays were constructed on fluorine-doped tin oxide (FTO) via a controllable hydrothermal route and a magnetron sputtering method with a variety of TiO2 arrays decorated by Ag nanoparticles. Effects of different TiO2 arrays on the microstructure, composition, and optical properties of the samples were revealed. As surface enhanced Raman scattering (SERS) active substrates, we discussed the sensitivity and reproducibility of Ag/TiO2 nanostructure arrays for Rhodamine 6G (R6G) molecule detection. It was found that TiO2 nanosheet (TiO2(S)) array as a supporting made Ag nanoparticles have a uniform and continuous distribution, which achieved much higher SERS signals. The obtained Ag/TiO2(S) substrate had an improved enhancement factor (EF) of 4.31×105 compared with the other Ag/TiO2 nanostructure arrays of nanorods, nanotubes, and nanotrees. Furthermore, Ag/TiO2(S) active substrate showed good reproducibility with low relative standard deviation (RSD) values. Such a remarkable SERS activity could be due to the synergistic effect of electromagnetic (EM) enhancement and charge transfer (CT) enhancement. Moreover, the TiO2(S) array with high-exposed {101} facets provided a large adhesion area and generated a strong interaction with external atoms, which would produce high-density "hot spots" of SERS.

12.
Trends Hear ; 24: 2331216520960053, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32965182

RESUMO

It is of clinical interest to estimate pure-tone thresholds from potentially available objective measures, such as stimulus-frequency otoacoustic emissions (SFOAEs). SFOAEs can determine hearing status (normal hearing vs. hearing loss), but few studies have explored their further potential in predicting audiometric thresholds. The current study investigates the ability of SFOAEs to predict hearing thresholds at octave frequencies from 0.5 to 8 kHz. SFOAE input/output functions and pure-tone thresholds were measured from 230 ears with normal hearing and 737 ears with sensorineural hearing loss. Two methods were used to predict hearing thresholds. Method 1 is a linear regression model; Method 2 proposed in this study is a back propagation (BP) network predictor built on the bases of a BP neural network and principal component analysis. In addition, a BP network classifier was built to identify hearing status. Both Methods 1 and 2 were able to predict hearing thresholds from 0.5 to 8 kHz, but Method 2 achieved better performance than Method 1. The BP network classifiers achieved excellent performance in determining the presence or absence of hearing loss at all test frequencies. The results show that SFOAEs are not only able to identify hearing status with great accuracy at all test frequencies but, more importantly, can predict hearing thresholds at octave frequencies from 0.5 to 8 kHz, with best performance at 0.5 to 4 kHz. The BP network predictor is a potential tool for quantitatively predicting hearing thresholds, at least at 0.5 to 4 kHz.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32975708

RESUMO

PURPOSE: Resistance to paclitaxel remains a major challenge in treating breast cancer. Our preclinical study suggested that TEKT4 germline variations in breast cancer are associated with paclitaxel resistance and increase vinorelbine sensitivity. This clinical trial compared the efficacy of paclitaxel and vinorelbine in breast cancer neoadjuvant chemotherapy. METHODS: In this open-label, single-center, phase II trial, female patients with human epidermal growth factor receptor 2 (HER2)-negative, stage IIB-IIIC breast cancer harboring TEKT4 germline variations were randomly assigned to the paclitaxel plus epirubicin (PE) or vinorelbine plus epirubicin (NE). The primary endpoint was the pathologic complete response (pCR) rate, and the secondary endpoints were the objective response rate (ORR) and safety. Targeted sequencing of a panel comprising 484 breast-related genes was performed to identify pCR-associated somatic mutations in each group. RESULTS: 91 Patients were assigned to PE (46 patients) or NE (45 patients). NE numerically increased the pCR rate (22.2% versus 8.7%, P = 0.074). The ORRs for NE and PE were 82.2% and 76.1%, respectively. Interestingly, NE (15.4%) showed a significantly higher pCR rate than PE (0%) in the hormone receptor (HR)-positive subgroup (P = 0.044). Both regimens were well tolerated, with grade 3 and 4 toxicities reported at the expected levels. The biomarker analysis showed that UNC13D mutation predicted the pCR rate in NE (P = 0.011). CONCLUSIONS: Although the primary endpoint was not met, NE might bring clinical benefit to HR-positive patients or patients simultaneously carrying UNC13D mutations.

14.
Int J Audiol ; : 1-11, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32959697

RESUMO

OBJECTIVE: This study aimed to maximise the ability of stimulus-frequency otoacoustic emissions (SFOAEs) to predict hearing status and thresholds based on machine-learning models. DESIGN: SFOAE data and audiometric thresholds were collected at octave frequencies from 0.5 to 8 kHz. Support vector machine, k-nearest neighbour, back propagation neural network, decision tree, and random forest algorithms were used to build classification models for status identification and to develop regression models for threshold prediction. STUDY SAMPLE: About 230 ears with normal hearing and 737 ears with sensorineural hearing loss. RESULTS: All classification models yielded areas under the receiver operating characteristic curve of 0.926-0.994 at 0.5-8 kHz, superior to the previous SFOAE study. The regression models produced lower standard errors (8.1-12.2 dB, mean absolute errors: 5.53-8.97 dB) as compared to those for distortion-product and transient-evoked otoacoustic emissions previously reported (8.6-19.2 dB). CONCLUSIONS: SFOAEs using machine-learning approaches offer promising tools for the prediction of hearing capabilities, at least at 0.5-4 kHz. Future research may focus on further improvements in accuracy and reductions in test time to improve clinical utility.

15.
J Cardiovasc Pharmacol ; 76(5): 602-609, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32868626

RESUMO

Heart failure (HF) affects around 100 million people and is a staggering burden for health care system worldwide. Rapid and sustained activation of inflammatory response is an important feature of HF after myocardial infarction. Sympathetic overactivation is also an important factor in the occurrence and progression of HF. The beneficial effect of renal denervation (RDN) has been demonstrated in HF. In the current study, we hypothesized that RDN improves cardiac function in HF canine models due to acute myocardial infarction (AMI) and reduced inflammation might be involved. Twenty-four beagles were randomized into the control (n = 8), HF (n = 8), and HF + RDN group (n = 8). The HF model after AMI was established by embolization the anterior descending distal artery with anhydrous ethanol in the HF and HF + RDN group. Bilateral renal artery ablation was performed in the HF + RDN group. Cardiac function, serum creatine kinase, creatine kinase-MB and NT-Pro BNP level, and expression of inflammation-related proteins in myocardial were examined. Because the paraventricular nucleus of the hypothalamus might be involved in inflammation-induced central neural excitation in HF and plays an important role in regulating extracellular fluid volume and sympathetic activity, expression of inflammation-related proteins in hypothalamus was also examined. AMI and post-AMI HF model was created successfully. Compared with the HF group, dogs in the HF + RDN group showed better cardiac function 4 weeks after AMI: lower left ventricular end-diastolic pressure, left ventricular end-diastolic dimension, and left ventricular end-systolic dimension and higher LEVF and left ventricular systolic pressure (P < 0.05 for all) were observed in the HF + RDN group. In addition, dogs in the HF + RDN group had slightly less ventricular fibrosis. Interestingly, RDN had lower expression of inflammation-related proteins including interleukin-6, tumor necrosis factors-α, nuclear factor κB, and monocyte chemotactic protein 1 (P < 0.05 for all) in both myocardial tissue and hypothalamus. RDN can improve cardiac function in dogs with HF after myocardial infarction. Our results suggested that RDN might affect cytokine-induced central neural excitation in HF and later affect sympathetic activity. Our results suggested a potential beneficial mechanism of RDN independent of mechanism involving renal afferent and efferent sympathetic nerves.

16.
Chron Respir Dis ; 17: 1479973120957676, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32909821

RESUMO

Bilirubin exerts antioxidant activity that has been associated with respiratory diseases. However, the relationship between serum bilirubin levels and idiopathic pulmonary fibrosis (IPF) is not clear. Therefore, in this study, we evaluated the relationship between serum bilirubin levels and the severity as well as the prognosis of IPF. One hundred and forty-six patients with IPF and 69 healthy individuals as the control group were enrolled as a derivation cohort. Routine blood examination and pulmonary function tests were performed and serum bilirubin levels were measured. To validate the value of serum bilirubin levels to predict the survival of patients with IPF, 40 additional IPF patients were included as a validation cohort. IPF patients were followed-up. Patients with IPF had significantly lower levels of serum total bilirubin (TBIL) and direct bilirubin (DBIL) than those in the control group (P < 0.05). Patients with acute exacerbation of IPF (AE-IPF) had significantly lower levels of serum TBIL and IBIL than those in patients with stable IPF (P < 0.05). The area under the receiver operating characteristic curve (AUROC) of serum TBIL levels for the prediction of the incidence of AE-IPF was 0.72 (95% CI: 0.56-0.87, P = 0.0057). The best cutoff value of serum TBIL level to predict the survival of patients with IPF was 8.8 µmol/l (AUC = 0.75, 95% CI: 0.64-0.87, P = 0.022). The log-rank test showed a significant difference in survival between the two groups (TBIL ≤8.8 µmol/l and TBIL >8.8 µmol/l) in derivation and validation cohort. Cox multiple regression analysis indicated that serum TBIL levels were an independent prognostic factor for IPF prognosis (HR = 0.582, P = 0.026). Serum TBIL levels might be useful for reflecting the severity and predicting the survival of patients with IPF.

17.
mSystems ; 5(5)2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963100

RESUMO

Apoptosis is generally considered the first line of defense against viral infection. However, the role of apoptosis in the interactions between plant viruses and their insect vectors has rarely been investigated. By studying plant DNA viruses of the genus Begomovirus within the family Geminiviridae, which are transmitted by whiteflies of the Bemisia tabaci species complex in a persistent manner, we revealed that virus-induced apoptosis in insect vectors can facilitate viral accumulation and transmission. We found that infection with tomato yellow leaf curl virus activated the apoptosis pathway in B. tabaci Suppressing apoptosis by inhibitors or silencing caspase-3 significantly reduced viral accumulation, while the activation of apoptosis increased viral accumulation in vivo Moreover, the positive effect of whitefly apoptosis on virus accumulation and transmission was not due to its cross talk with the autophagy pathway that suppresses begomovirus infection in whiteflies. We further showed that viral replication, rather than the viral coat protein, is likely the critical factor in the activation of apoptosis by the virus. These novel findings indicate that similarly to many animal and a few plant RNA viruses, plant DNA viruses may activate apoptosis in their insect vectors leading to enhanced viral accumulation and transmission.IMPORTANCE Of the approximately 1,100 known plant viruses, about one-third are DNA viruses that are vectored by insects. Plant virus infections often induce cellular and molecular responses in their insect vectors, which can, in many cases, affect the spread of viruses. However, the mechanisms underlying vector responses that affect virus accumulation and transmission are poorly understood. Here, we examined the role of virus-induced apoptosis in the transmission of begomoviruses, a group of single-stranded plant DNA viruses that are transmitted by whiteflies and cause extensive damage to many crops worldwide. We demonstrated that virus infection can induce apoptosis in the insect vector conferring protection to the virions from degradation, leading to enhanced viral accumulation and transmission to host plants. Our findings provide valuable clues for designing new strategies to block the transmission of insect-vectored plant viruses, particularly plant DNA viruses.

18.
Proc Natl Acad Sci U S A ; 117(38): 23695-23706, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32907941

RESUMO

Long noncoding RNAs (lncRNAs) involved in the regulation of antiviral innate immune responses need to be further identified. By functionally screening the lncRNAs in macrophages, here we identified lncRNA Malat1, abundant in the nucleus but significantly down-regulated after viral infection, as a negative regulator of antiviral type I IFN (IFN-I) production. Malat1 directly bound to the transactive response DNA-binding protein (TDP43) in the nucleus and prevented activation of TDP43 by blocking the activated caspase-3-mediated TDP43 cleavage to TDP35. The cleaved TDP35 increased the nuclear IRF3 protein level by binding and degrading Rbck1 pre-mRNA to prevent IRF3 proteasomal degradation upon viral infection, thus selectively promoting antiviral IFN-I production. Deficiency of Malat1 enhanced antiviral innate responses in vivo, accompanying the increased IFN-I production and reduced viral burden. Importantly, the reduced MALAT1, augmented IRF3, and increased IFNA mRNA were found in peripheral blood mononuclear cells (PBMCs) from systemic lupus erythematosus (SLE) patients. Therefore, the down-regulation of MALAT1 in virus-infected cells or in human cells from autoimmune diseases will increase host resistance against viral infection or lead to autoinflammatory interferonopathies via the increased type I IFN production. Our results demonstrate that the nuclear Malat1 suppresses antiviral innate responses by targeting TDP43 activation via RNA-RBP interactive network, adding insight to the molecular regulation of innate responses and autoimmune pathogenesis.


Assuntos
Proteínas de Ligação a DNA , Imunidade Inata/imunologia , Fator Regulador 3 de Interferon , RNA Longo não Codificante , Adolescente , Adulto , Animais , Antivirais/imunologia , Antivirais/metabolismo , Células Cultivadas , Proteínas de Ligação a DNA/imunologia , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Fator Regulador 3 de Interferon/imunologia , Fator Regulador 3 de Interferon/metabolismo , Interferon Tipo I/imunologia , Interferon Tipo I/metabolismo , Leucócitos Mononucleares/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , RNA Longo não Codificante/imunologia , RNA Longo não Codificante/metabolismo , Viroses/imunologia , Adulto Jovem
19.
J Enzyme Inhib Med Chem ; 35(1): 1631-1640, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32781863

RESUMO

Nuclear factor kappa B (NF-кB) inhibition represents a new therapeutic strategy for the treatment of neuroinflammatory diseases. In this study, a series of 3,4-dihydronaphthalen-1(2H)-one (DHN; 6a-n, 7a-c) derivatives were synthesised and characterised by NMR and HRMS. We assessed the toxicity and anti-neuroinflammatory properties of these compounds and found that 6m showed the greatest anti-neuroinflammatory properties, with relatively low toxicity. Specifically, 6m significantly reduced reactive oxygen species production, down-regulated the expression of NOD-like receptor pyrin domain-containing protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1 and prevented lipopolysaccharide-stimulated BV2 microglia cells polarisation towards an M1 phenotype. Furthermore, 6m significantly decreased IκBα and NF-кB p65 phosphorylation, thus inhibiting the NF-кB signalling pathway. This suggests that 6m may be explored as a functional anti-neuroinflammatory agent for the treatment of inflammatory diseases in the central nervous system, such as multiple sclerosis, traumatic brain injury, stroke and spinal cord injury.

20.
Environ Pollut ; 266(Pt 2): 115336, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32836048

RESUMO

Black-spotted frogs and bullfrogs from an e-waste polluted area were collected and examined for legacy and emerging organophosphorus flame retardants (PFRs) and plasticizers. Total concentrations of PFRs and plasticizers were 0.62-15 ng/g wet weight (ww) and 316-4904 ng/g ww in muscles, 2.2-59 ng/g ww and 127-5757 ng/g ww in eggs and gonads, and 1.2-15 ng/g ww and 51-1510 ng/g ww in oviducts, respectively. For muscle tissues, concentrations of ∑PFRs, triethyl phosphate, tris-(2-chloroethyl) phosphate, and tris-(chloro-2-propyl) phosphate were significantly higher in the males than females (p < 0.05). However, for reproductive tissues, eggs exhibited higher levels of those contaminants than gonads (p < 0.05). No significant sex difference in levels of plasticizers was observed in muscles. In contrast, levels for (2-ethylhexyl) phthalate, di-n-butyl phthalate, and di-iso-butyl phthalate in gonads were significantly higher than those in eggs (p < 0.05). Significantly negative linear correlations between maternal transfer ratios and log KOW were found in female frogs. Paternal transfer potentials were first significantly and positively correlated to log KOW (<6) and then decreased afterward in the males. These results indicated that parental transfer was answer for the sex-specific accumulation of PFRs and plasticizers in frogs.


Assuntos
Retardadores de Chama/análise , Animais , Ovos/análise , Monitoramento Ambiental , Feminino , Masculino , Organofosfatos , Compostos Organofosforados , Plastificantes/análise , Caracteres Sexuais
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