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1.
Singapore Med J ; 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32227795

RESUMO

Radiation thyroiditis resulting from radioactive iodine-131 treatment for Graves' disease is an uncommon complication. Although a majority of patients are asymptomatic or manifest mild symptoms that can be managed conservatively, published literature describing severe radiation thyroiditis resulting in significant morbidity is lacking. We herein report six patients with severe radiation thyroiditis that resulted in hospitalisation, including an unusual complication of myopericarditis.

2.
J Chem Inf Model ; 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32233478

RESUMO

De novo drug design actively seeks to use sets of chemical rules for the fast and efficient identification of structurally new chemotypes with the desired set of biological properties. Fragment-based de novo design tools have been successfully applied in the discovery of noncovalent inhibitors. Nevertheless, these tools are rarely applied in the field of covalent inhibitor de-sign. Herein, we present a new protocol, called Cov_FB3D, which aims to the 'in silico' assembly of potential novel covalent inhibitors by identifying the active fragments in the covalently binding site of the target protein. In this protocol, we propose a BA-SAMP strategy, which combines the noncovalent moiety score with the X-score as MM level, and the covalent can-didate score with the PM7 as QM level. The synthetic accessibility of each suggested compound could be further evaluated with machine-learning-based synthetic complexity evaluation (SCScore). An in-depth test of this protocol against the crystal structures of 15 covalent complexes consisting of BTK-inhibitors, KRAS-inhibitors, EGFR-inhibitors, EphB1-inhibitors, MAGL-inhibitors and MAPK-inhibitors revealed that most of these inhibitors could be de novo repro-duced from the fragments by Cov_FB3D. The binding modes of most generated reference poses could accurately reproduce the known binding mode of most of the reference covalent adduct in the binding site (RMSD ≤ 2 Å). In particular, most of these inhibitors were ranked in the top 2% using the BA-SAMP strategy. Notably, the novel human ALDOA inhibitor (T1) with potent inhibitory activity (0.34 ± 0.03 µM) and greater synthetic accessibility was successfully de novo designed by this protocol. The positive results confirm the abilities of Cov_FB3D protocol.

3.
Mol Metab ; : 100982, 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32247924

RESUMO

OBJECTIVES: The streptozotocin (STZ) model is widely used in diabetes research. However, the cellular and molecular states of pancreatic endocrine cells in this model remain unclear. This study aims to explore the molecular characteristics of islet cells treated with STZ and to re-evaluate ß-cell dysfunction and regeneration in the STZ model. METHODS: We performed single-cell RNA sequencing of pancreatic endocrine cells from STZ-treated mice. High-quality sequencing data from 2,999 cells were used to identify clusters by Louvain clustering analysis. Principal component analysis (PCA), t-distributed stochastic neighbor embedding (t-SNE), uniform manifold approximation and projection (UMAP), force-directed layout (FDL) and differential expression analysis were performed to define the heterogeneity and transcriptome changes in islet cells. In addition, qPCR and immunofluorescence were used to confirm findings from the sequencing data. RESULTS: Untreated ß-cells were divided into two populations at the transcriptomic level, a large high-Glut2 expression (Glut2high) population and a small low-Glut2 expression (Glut2low) population. At the transcriptomic level, Glut2low ß-cells in adult mice do not represent a developmentally immature state, although a fraction of genes associated with ß-cell maturation and function were downregulated in Glut2low cells. After a single high-dose STZ treatment, most of Glut2high cells were killed, but Glut2low cells survived and over time changed to a distinct cell state. We did not observe conversion of Glut2low to Glut2high ß-cells up to 9 months after STZ treatment. In addition, we did not detect transcriptomic changes in non-ß endocrine cells or a direct trans-differentiation pathway from the α-cell lineage to the ß-cell lineage in the STZ model. CONCLUSIONS: We identified the heterogeneity of ß-cells in both physiological and pathological conditions. However, we did not observe conversion of Glut2low to Glut2high ß-cells, transcriptomic changes in non-ß endocrine cells, or direct trans-differentiation from the α-cell lineage to the ß-cell lineage in the STZ model. Our results clearly define the state of islet cells treated with STZ and allow us to re-evaluate the STZ model widely used in diabetes studies.

4.
Nano Lett ; 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32163291

RESUMO

Two-dimensional spiral plasmonic structures have emerged as a versatile approach to generate near-field vortex fields with tunable topological charges. We demonstrate here a far-field approach to observe the chiral second-harmonic generation (SHG) at designated visible wavelengths from a single plasmonic vortex metalens. This metalens comprises an Archimedean spiral slit fabricated on atomically flat aluminum epitaxial film, which allows for precise tuning of plasmonic resonances and subsequent transfer of two-dimensional materials on top of the spiral slit. The nonlinear optical measurements show a giant SHG circular dichroism. Furthermore, we have achieved an enhanced chiral SHG conversion efficiency (about an order of magnitude greater than the bare aluminum lens) from monolayer tungsten disulfide (WS2)/aluminum metalens, which is designed at the C-exciton resonance of WS2. Since the C-exciton is not a valley exciton, the enhanced chiral SHG in this hybrid system originates from the plasmonic vortex field-enhanced SHG under the optical spin-orbit interaction.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32182891

RESUMO

Environmental factors have been linked to many diseases and health conditions, but reliable assessment of environmental exposures is challenging. Developing biomarkers of environmental exposures, rather than relying on self-report, will improve our ability to assess the association of such exposures with disease. Epigenetic markers, most notably DNA methylation, have been identified for some environmental exposures, but identification of markers for additional exposures is still needed. The rationale behind the Markers for Environmental Exposures (MEE) Study was to (1) identify biomarkers, especially epigenetic markers, of environmental exposures, such as pesticides, air/food/water contaminants, and industrial chemicals that are commonly encountered in the general population; and (2) support the study of potential relationships between environmental exposures and health and health-related factors. The MEE Study is a cross-sectional study with potential for record linkage and follow-up. The well-characterized cohort of 400 postmenopausal women has generated a repository of biospecimens, including blood, urine, and saliva samples. Paired data include an environmental exposures questionnaire, a breast health questionnaire, dietary recalls, and a food frequency questionnaire. This work describes the rationale, study design, and cohort characteristics of the MEE Study. In addition to our primary research goals, we hope that the data and biorepository generated by this study will serve as a resource for future studies and collaboration.

6.
Sci Rep ; 10(1): 4997, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32193490

RESUMO

Sacrospinous ligament fixation (SSLF) is one of the most utilized surgeries in the management of pelvic organ prolapse (POP). We conducted a large-series study of SSLF in a tertiary center by an experienced urogynecologic team. The 453 women with POP who underwent SSLF at National Taiwan University Hospital in the period from 2002 to 2015 are reviewed. All patients received unilateral SSLF with Veronikis ligature carrier. Concomitant anterior colporrhaphy was performed in 75.3% of the cases and posterior colporrhaphy in 78.6%. The mean operation time was 92.3 ± 31.5 minutes. The intraoperative blood loss was 92.3 ± 91.4 ml. The objective cure rate was 82.5%, and 79 (17.5%) patients recurred. The Kaplan-Meier recurrence-free analysis showed a steep decline during the first postoperative year, and the yearly number of recurrent patients decreased as the follow-up period proceeded. A comparison of the site of recurrence found that anterior compartment prolapse was the most common with 57 cases (12.6%). Paravaginal repair is frequently implemented in the management of recurrent anterior prolapse. In conclusion, SSLF provides excellent support to the apex compartment, and our long-term results show that the anterior compartment is the most commonly encountered type of POP recurrence.

7.
J Clin Sleep Med ; 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32208133

RESUMO

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) has been associated with increased cancer incidence and mortality. The aim of this study was to investigate cancer-related mortality, overall survival and progression free survival in patients with suspected OSA and lung cancer. METHODS: This was a case series analysis of lung cancer from a sleep cohort with suspected OSA between 2009 and 2014. The apnea- hypopnea index (AHI), Tsat90% (hypoxia index) and survival outcome were recorded. Immunohistochemistry was used to analyze HIF-1α and VEGF expression in tumor pathology. RESULTS: In the sleep cohort comprising 8261 patients, a total of 23 patients had lung cancer. The incidence of lung cancer was significantly higher in the sleep cohort than in the entire adult population in Taiwan (242.1 vs 51.5 per 105 persons, P< 0.01). The 3-year cancer-related mortality was 25% in AHI < 15, 50% in AHI 15 to 29 and 80% in AHI ≥ 30 (chi-squared test for trend P =0.03). In Kaplan-Meier survival analysis, patients with stage III-IV lung cancer and AHI< 30 exhibited significantly better overall survival (P = 0.02) and progression free survival (P = 0.02) than patients with severe OSA. Overexpression of HIF-1α and VEGF was shown in 63 % and 45 % of lung tumor samples. Overexpression of HIF-1α was positively associated with AHI (P = 0.04). CONCLUSIONS: In this preliminary case series, severe OSA is associated with an increased risk of cancer mortality in patients with stage III-IV lung cancer. AHI was significantly associated with HIF-1α overexpression.

8.
J Urol ; : 101097JU0000000000001020, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32191585

RESUMO

PURPOSE: This is the first report of the development and performance of a platform that interrogates small non-coding RNAs (sncRNA) isolated from urinary exosomes (the miR Sentinel™ Tests): the Sentinel™ PCa Test, that classifies patients with prostate cancer from subjects with no evidence of prostate cancer, the miR Sentinel™ CS Test, that stratifies prostate cancer patients between those with low risk prostate cancer (GG1) from those with intermediate and high risk disease (GG2-5), and the miR Sentinel™ HG Test, that stratifies prostate cancer patients between those with low- and favorable intermediate-risk prostate cancer (GG1 or GG2) versus those with high risk (GG3-5) disease. METHOD: sncRNAs were extracted from urinary exosomes of 235 participants and interrogated on miR 4.0 microarrays. Using proprietary Selection and Classification Algorithms, informative sncRNAs were selected to customize an interrogation OpenArray™ platform that forms the basis of the Tests. The Tests were validated using a case-control sample of 1436 subjects. RESULTS: The performance of the miR Sentinel™ PCa Test demonstrated sensitivity = 94% and specificity = 92%. The Sentinel™ CS Test demonstrated a sensitivity = 93% and specificity = 90% for prediction of the presence of GG≥2 cancer, and the Sentinel™ HG Test demonstrated a sensitivity = 94% and specificity = 96% for the prediction of the presence of GG≥3 cancer. CONCLUSIONS: The Sentinel™ PCa, CS and HG Tests, demonstrated high levels of sensitivity and specificity, highlighting the utility of interrogation of urinary exosomal sncRNAs for non-invasively diagnosing and classifying prostate cancer with high precision.

9.
JCI Insight ; 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32191644

RESUMO

C5a is a potent inflammatory mediator, which binds C5aR1 and C5aR2. Although pathogenic roles of C5a/C5aR1 axis in inflammatory disorders are well-documented, the roles for C5a/C5aR2 axis in inflammatory disorders and underlying mechanisms remain unclear. Here, we show that C5a/C5aR2 axis contributes to renal inflammation and tissue damage in a mouse model of acute pyelonephritis. Compared with WT littermates, C5ar2-/- mice had significantly reduced renal inflammation, tubular damage and renal bacterial load following bladder inoculation with uropathogenic E coli. The decrease in inflammatory responses in the kidney of C5ar2-/- mice was correlated with reduced intrarenal levels of high mobility group box 1 protein (HMGB1), NLRP3 inflammasome components, cleaved caspase-1 and IL-1ß. In vitro, C5a stimulation of macrophages from C5ar1-/- mice (lacking C5aR1 but expressing C5aR2) led to significant upregulation of HMGB1 release, NLRP3/caspase-1 inflammasome activation and IL-1ß secretion. Furthermore, blockade of HMGB1 significantly reduced C5a-mediated upregulation of NLRP3/caspase-1 inflammasome activation and IL-1ß secretion in the macrophages, implying a HMGB1-dependent upregulation of NLRP3/caspase-1 inflammasome activation in macrophages. Our findings demonstrate a pathogenic role for C5a/C5aR2 axis in renal injury following renal infection and suggest that C5a/C5aR2 axis contributes to renal inflammation and tissue damage through up-regulation of HMGB1 and NLRP3/caspase-1 inflammasome.

10.
Trends Cancer ; 6(4): 265-267, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32209439

RESUMO

Patient-derived organoids can recapitulate parental tumor heterogeneity. In a recent study in Cell, Jacob et al. cultivated glioblastoma organoids (GBOs) to mimic tumor heterogeneity and chimeric antigen receptor (CAR)-T cell immunotherapy, applied it for xenograft establishment and drug testing, and generated a biobank for the timely start of post-operation therapy.

11.
Heart Lung ; 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32171586

RESUMO

BACKGROUND: Hypertension is the major attributable risk factor for cardiovascular disease. The effect of Tai Chi on essential hypertension (EH) is contentious. OBJECTIVES: In this study, we investigated the effects of Tai Chi on the risk factors for cardiovascular disease and quality of life in adults with EH. METHODS: Using data collected from 15 databases up to December 2018, we meta-analyzed randomized controlled trials of the effect of Tai Chi on EH. RESULTS: Tai Chi exercise was associated with lower systolic blood pressure (SBP) (WMD -12.47, 95%CI -16.00 to -8.94, P < 0.001) and diastolic blood pressure (DBP) (WMD -6.46, 95%CI -8.28 to -4.64, P < 0.001); better quality of life (SMD 0.62, 95% CI 0.35 to 0.90, P < 0.001); lower lipid profiles, including total cholesterol (WMD -0.49, 95% CI -0.62 to -0.37, P < 0.001), triglycerides (WMD -0.49, 95% CI -0.92 to -0.07, P = 0.02), and low-density lipoprotein-cholesterol (LDL-C) (WMD -0.86, 95% CI -1.30 to -0.43, P < 0.001); and lower blood glucose (WMD -0.91, 95% CI -1.59 to -0.23, P = 0.009). Tai Chi had no significant effect on high-density lipoprotein-cholesterol (WMD -0.92, 95% CI -2.21 to -0.37, P = 0.16). CONCLUSIONS: Tai Chi lowers blood pressure, total cholesterol, triglycerides, LDL-C, and blood glucose and significantly increases the quality of life in adults with EH. There is strong evidence for the short-term efficacy of Tai Chi exercises. Larger well-designed RCTs focused on the long-term effect of Tai Chi exercises and patient adherence are needed.

12.
Plant Physiol ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32152212

RESUMO

Plants have evolved effective strategies to defend themselves against pathogen invasion. Starting from the plasma membrane with the recognition of microbe-associated molecular patterns (MAMPs) via pattern recognition receptors, internal cellular signaling pathways are induced to ultimately fend off the attack. Phospholipase D (PLD) hydrolyzes membrane phospholipids to produce phosphatidic acid (PA), which has been proposed to play a second messenger role in immunity. The Arabidopsis (Arabidopsis thaliana) PLD family consists of 12 members and for some a specific function in resistance towards a subset of pathogens has been shown. We demonstrate here that Arabidopsis PLDγ1, but not its close homologs PLDγ2 and PLDγ3, is specifically involved in plant immunity. Genetic inactivation of PLDγ1 resulted in increased resistance towards the virulent bacterium Pseudomonas syringae pv. tomato DC3000 and the necrotrophic fungus Botrytis cinerea. As pldγ1 mutant plants responded with elevated levels of reactive oxygen species to MAMP-treatment, a negative regulatory function for this PLD isoform is proposed. Importantly, PA levels in pldγ1 mutants were not affected compared to stressed wild-type plants, suggesting that alterations in PA levels are not likely the cause for the enhanced immunity in the pldγ1 line. Instead, the plasma-membrane-attached PLDγ1 protein colocalized and associated with the BAK1-INTERACTING RECEPTOR-LIKE KINASES BIR2 and BIR3, which are known negative regulators of pattern-triggered immunity. Moreover, complex formation of PLDγ1 and BIR2 was further promoted upon MAMP-treatment. Hence, we propose that PLDγ1 acts as a negative regulator of plant immune responses in complex with immunity-related proteins BIR2 and BIR3.

13.
ChemSusChem ; 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32112521

RESUMO

The photocatalytic reduction of N2 to NH3 is considered a promising strategy to alleviate human need for accessible nitrogen and environmental pollution, for which developing a photocatalyst is an effective method to complete the transformation of this process. We firstly design a series of highly efficient and stable polyoxometalates (POMs)-based zeolitic imidazolate framework-67 (ZIF-67) photocatalysts for N2 reduction. ZIF-67 can effectively fix N2 owing to its porosity. Integration of POMs cluster contributes enormous advantages in terms of broadening the absorption spectrum to improve sunlight utilization, enhance the stability of the materials, effectively inhibit the recombination of photo-generated electron-hole pairs, and reduce charge-transfer impedance. POMs can absorb light to convert into reduced POMs, which have stronger reducing ability to provide ample electrons to reduce N2 . The reduced POMs can recover their oxidation state through contact with an oxidant, which forms a self-recoverable and recyclable photocatalytic fixing N2 system. The photocatalytic activity enhances with the increasing number V substitutions in the POMs. Satisfactorily, ZIF-67@K11 [PMo4 V8 O40 ] (PMo4 V8 ) displays the most significant photocatalytic N2 activity with a NH3 yield of 149.0 µmol L-1 h-1 , which is improved by 83.5 % (ZIF-67) and 78.9 % (PMo4 V8 ). The introduction of POMs provides new insights for the design of high-performance photocatalyst nanomaterials to reduce N2 .

14.
Behav Brain Res ; 386: 112586, 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32194187

RESUMO

Previous neuroimaging studies have reported differences in regional brain activation between males and females during stop signal task performance, suggesting the presence of sex-linked differences in brain network organization of inhibitory ability. Despite a growing literature on sex differences during stop signal task performance, a consensus still has not been reached due to variations in task design and analysis methods. Due to these disparate findings we used up to date stop signal task methods to compare behavioral performance and associated brain activation between males and females using an event-related functional magnetic resonance imaging design. We observed that males were faster in inhibiting their responses, but females exhibited marked increased in stopping network activation, in addition to increased activation of the anterior insula and left amygdala. These findings suggest that males and females process stop signals differently.

15.
Microb Pathog ; 144: 104169, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32205210

RESUMO

Viral myocarditis (VMC) is a type of inflammation affecting myocardial cells caused by viral infection and has been an important cause of dilated cardiomyopathy (DCM) worldwide. Type B3 coxsackievirus (CVB3), a non-enveloped positive-strand RNA virus of the Enterovirus genus, is one of most common agent of viral myocarditis. Till now, effective treatments for VMC are lacking due to lack of drugs or vaccine. Lithium chloride (LiCl) is applied in the clinical management of manic depressive disorders. Accumulating evidence have demonstrated that LiCl, also as an effective antiviral drug, exhibited antiviral effects for specific viruses. However, there are few reports of evaluating LiCl's antiviral effect in mice model. Here, we investigated the inhibitory influence of LiCl on the CVB3 replication in vitro and in vivo and the development of CVB3-induced VMC. We found that LiCl significantly suppressed CVB3 replication in HeLa via inhibiting virus-induced cell apoptosis. Moreover, LiCl treatment in vivo obviously inhibited virus replication within the myocardium and alleviated CVB3-induced acute myocarditis. Collectively, our data demonstrated that LiCl inhibited CVB3 replication and negatively regulated virus-triggered inflammatory responses. Our finding further expands the antiviral targets of LiCl and provides an alternative agent for viral myocarditis.

16.
Org Lett ; 22(7): 2574-2578, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32167308

RESUMO

(±)-Dispirocochlearoids A-C (1-3), meroterpenoids with a 6/6/5/6/6/6 ring system, were isolated from Ganoderma cochlear. 1-3 are selective COX-2 inhibitors with an IC50 value of (-)-2 at 386 nM. Site-directed mutagenesis identified His351 as a COX-2 active site. In vivo anti-inflammatory activities of (-)-2 were performed against acute lung injury in mice.

17.
Medicina (Kaunas) ; 56(2)2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32079310

RESUMO

BACKGROUND: Osteoporotic spinal fractures commonly occur in elderly patients with low bone mineral density. In these cases, percutaneous vertebroplasty or percutaneous kyphoplasty can provide significant pain relief and improve mobility. However, studies have reported both the recurrence of vertebral compression fractures at the index level after vertebroplasty and the development of new vertebral fractures at the adjacent level that occur without any additional trauma. Pedicle screw fixation combined with percutaneous vertebroplasty has been proposed as an effective procedure for addressing osteoporotic thoracolumbar fractures. However, in osteoporotic populations, pedicle screws can loosen, pullout, or migrate. Currently, the efficacy of cortical bone trajectory screw fixation for osteoporotic fractures remains unclear. Thus, we assessed the effects of using cortical bone trajectory instrumentation with vertebroplasty on patient outcomes. METHOD: We retrospectively reviewed data from 12 consecutively sampled osteoporotic thoracolumbar fracture patients who underwent cortical bone trajectory instrumentation with vertebroplasty. Patients were enrolled beginning in October 2015 and were followed for >24 months. RESULT: The average age was 74 years, and the average dual-energy x-ray absorptiometry T-score was -3.6. The average visual analog scale pain scores improved from 8 to 2.5 after surgery. The average blood loss was 36.25 mL. All patients regained ambulation and experienced reduced pain post-surgery. No recurrent fractures or instrument failures were recorded during follow-up. CONCLUSIONS: Our findings suggest that cortical bone trajectory instrumentation combined with percutaneous vertebroplasty may be a good option for treating osteoporotic thoracolumbar fractures, as it can prevent recurrent vertebral fractures or related kyphosis in sagittal alignment.

18.
J Virol ; 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32102886

RESUMO

Respiratory syncytial virus (RSV) is an enveloped RNA virus which is responsible for approximately 80% of lower respiratory tract infections in children. Current lines of evidence have supported the functional involvement of long non-coding RNA (lncRNA) in many viral infectious diseases. However, the overall biological effect and clinical role of lncRNAs in RSV infection remain unclear. In this study, lncRNAs related to respiratory virus infection were obtained from lncRNA database. And we collected 144 clinical sputum specimens to identify lncRNAs related to RSV infection. qPCR detection indicated that the expression of lncRNA NRAV in RSV-positive patients was significantly lower than that in uninfected ones, but lncRNA PRINS, NEAT1, and NEST showed no difference in vivo and in vitro Meanwhile, over expression of Negative Regulator of Antiviral Response (NRAV) promoted RSV proliferation in A549 and BEAS-2B cells, and vice versa, indicating that the down-regulation of NRAV was part of the host antiviral defense. RNA FISH confirmed that NRAV was mainly located in the cytoplasm. Through RNA sequencing we found that Rab5c, which is a vesicle transporting protein, showed the same change trend as NRAV. Subsequent investigation revealed that NRAV was able to favor RSV production indirectly by sponging miR-509-3p so as to release Rab5c and facilitate vesicle transportation. The study provides a new insight into virus-host interaction through non-coding RNA, which may contribute to exploring potential antivirus target for respiratory virus.IMPORTANCE Mechanism of interaction between RSV and host non-coding RNAs has not been fully understood. In this study, we found that the expression of lncRNA NRAV was reduced in RSV-infected patients, and over-expression of NRAV facilitated RSV production in vitro, suggesting that the reduction of NRAV in RSV infection was part of the host antiviral response. We also found that NRAV competed with vesicle protein Rab5c for miR509-3p in cytoplasm, to promote RSV vesicle transport and accelerate RSV proliferation, thereby improving our understanding of the pathogenic mechanism of RSV infection.

20.
Sci Total Environ ; 711: 134416, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32000302

RESUMO

Nitrite accumulation in aquatic environments is a potential risk factor that disrupts multiple physiological functions in aquatic animals. In this study, the physiology, transcriptome and metabolome of the control group (LV-C), nitrite-tolerance group (LV-NT) and nitrite-sensitive group (LV-NS) were investigated to identify the stress responses and mechanisms underlying the nitrite tolerance of Litopenaeus vannamei. After LV-NT and LV-NS were subjected to nitrite stress, the hemocyanin contents were significantly decreased, and hepatopancreas showed severe histological damage compared with LV-C. Likewise, the antioxidant enzymes were also significantly changed after nitrite exposure. The transcriptome data revealed differentially expressed genes associated with immune system, cytoskeleton remodeling and apoptosis in LV-NT and LV-NS. The combination of transcriptomic and metabolomic analysis revealed nitrite exposure disturbed metabolism processes in L. vannamei, including amino acid metabolism, nucleotide metabolism and lipid metabolism. The multiple comparative analysis implicated that higher nitrite tolerance of LV-NT than LV-NS may be attributed to enhanced hypoxia inducible factor-1α expression to regulate energy supply and gaseous exchange. Moreover, LV-NT showed higher antioxidative ability, detoxification gene expression and enhanced fatty acids contents after nitrite exposure in relative to LV-NS. Collectively, all these results will greatly provide new insights into the molecular mechanisms underlying the stress responses and tolerance of nitrite exposure in L. vannamei.


Assuntos
Metabolômica , Penaeidae , Transcriptoma , Animais , Hepatopâncreas , Nitritos , Estresse Fisiológico
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