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1.
Biomed Pharmacother ; 121: 109634, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31731197

RESUMO

Accumulating studies have suggested that epicardial adipose tissue (EAT) play an important role in the pathogenesis of atrial fibrillation (AF), but few have characterized the underlying mechanism between their interactions. Recent evidence suggested that bioactive molecules secreted from EAT, including exosomes carrying long non-coding RNAs (lncRNAs), may modulate atrial remodeling. LncRNAs are associated with cardiovascular disorders, including AF, but their roles in EAT remain elusive. The aim of the present study was to investigate the expression profile of lncRNAs in EAT with AF. Differentially expressed lncRNAs and nearby mRNAs interaction networks were constructed. Epicardial adipose samples were collected from patients with persistent non-valvular AF (n = 6) and sinus rhythm (SR) (n = 6), and the expression of lncRNAs and mRNAs were profiled using RNA-sequencing method. A total of 46,577 transcripts, including 35,552 protein-coding pattern, corresponding to 15,404 genes in EAT, among which, 655 mRNAs (265 upregulated and 390 downregulated) and 57 lncRNAs (17 upregulated and 40 downregulated) were differentially expressed between AF and SR (P < 0.05; fold change>1.5). GO enrichment, KEGG pathway analysis and interaction network construction showed that these differentially expressed lncRNAs were enriched in functional categories, including metabolism and stress response, which might contribute to the pathogenesis of AF. Our study demonstrated a differentially expressed lncRNA profile in EAT with AF, and provide a novel insight into the interactions between EAT and AF.

2.
J Affect Disord ; 260: 557-568, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31539693

RESUMO

OBJECTIVE: This study mapped the topological configuration of the default mode network (DMN) in patients with depressive symptoms after acute ischemic stroke. METHODS: The study sample comprised 63 patients: 36 with poststroke depressive symptoms (PSD) and 37 without PSD matched according to age, gender and the severity of stroke. PSD was defined by a cutoff of ≥ 7 on the 15-item Geriatric Depression Scale (GDS). Resting-state functional magnetic resonance imaging (fMRI) was used to examine functional connectivity (FC) to reconstruct the DMN. Network based statistics estimated the FC differences of the DMN between the PSD and non-PSD groups. Graph theoretical approaches were used to characterize the topological properties of this network. RESULTS: The study sample mainly comprised patients with mild to moderate stroke. A widespread hyper-connected configuration of the functional DMN was characterized in PSD group. The orbital frontal, dorsolateral prefrontal, dorsal medial prefrontal and, ventromedial prefrontal corticis, the middle temporal gyrus and the inferior parietal lobule were the functional hubs related to PSD. The nodal topology in inferior parietal lobule and superior frontal gyrus, overlapping with dorsal medial prefrontal and, ventromedial prefrontal cortices, tended to be functionally integrated in patients with PSD. After False Discovery Rate correction, no significant difference between the PSD and non-PSD groups was found with respect to the global and nodal metrics of the DMN. However, the correlations between these altered network metrics and severity of PSD were lacking. LIMITATIONS: The diagnosis of PSD was based on the GDS score rather than established with a structured clinical interview. CONCLUSIONS: The DMN in PSD was functionally integrated and more specialized in some core hubs such as the inferior parietal lobule and dorsal prefrontal cortex. The configuration of the subnetwork like DMN may be more essential in the pathogenesis of PSD than single stroke lesions.

3.
Chemosphere ; 238: 124630, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31473530

RESUMO

Mercury (Hg) mining activities are an important anthropogenic source of atmospheric Hg. The Xunyang Hg mine located in Shaanxi Province is the largest active Hg producing centre in China. To understand the biogeochemical processes of atmospheric Hg through Hg mining activities, six groups of experimental pots were carefully designed to investigate the effect of Hg mining activities on Hg contamination from atmospheric deposition in the local surface soils. Based on the variations of Hg in the soil from the experimental pots, the deposition flux and loading of Hg in the Xunyang Hg mining district were investigated. The results showed that the average concentration of total gaseous mercury (TGM) as high as 193 ±â€¯122 ng m-3 was observed in the ambient air, which was orders of magnitude higher than that in remote areas. The average deposition flux and annual loading of atmospheric Hg were 72 mg m-2 y-1 and 10 t y-1, respectively. The dominant atmospheric Hg deposition is within a distance range of 6.0-12 km from the Hg retorting facility, accounting for approximately 85% of the total Hg loading. After 14 months of exposure, total mercury (THg) concentrations in the soil from the experimental pots increased 0.35-9.5 times, and the highest concentrations of methylmercury (MeHg) (3.7 ±â€¯2.9 µg kg-1) in soil were observed in February. Concentrations as high as 643 µg kg-1 THg and 13 µg kg-1 MeHg in rice were observed in the second experimental year. Elevated concentrations of both THg and MeHg in rice indicated that the newly deposited atmospheric Hg was bioavailable, readily methylated, and taken up by rice, suggesting that the ongoing Hg mining activities cause serious Hg contamination in the soil-rice ecosystem and posed a threat to local residents in the Xunyang Hg mining area.

4.
Mol Cancer ; 18(1): 174, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791342

RESUMO

BACKGROUND: Long noncoding RNAs (lncRNAs) play nonnegligible roles in the epigenetic regulation of cancer cells. This study aimed to identify a specific lncRNA that promotes the colorectal cancer (CRC) progression and could be a potential therapeutic target. METHODS: We screened highly expressed lncRNAs in human CRC samples compared with their matched adjacent normal tissues. The proteins that interact with LINRIS (Long Intergenic Noncoding RNA for IGF2BP2 Stability) were confirmed by RNA pull-down and RNA immunoprecipitation (RIP) assays. The proliferation and metabolic alteration of CRC cells with LINRIS inhibited were tested in vitro and in vivo. RESULTS: LINRIS was upregulated in CRC tissues from patients with poor overall survival (OS), and LINRIS inhibition led to the impaired CRC cell line growth. Moreover, knockdown of LINRIS resulted in a decreased level of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), a newly found N6-methyladenosine (m6A) 'reader'. LINRIS blocked K139 ubiquitination of IGF2BP2, maintaining its stability. This process prevented the degradation of IGF2BP2 through the autophagy-lysosome pathway (ALP). Therefore, knockdown of LINRIS attenuated the downstream effects of IGF2BP2, especially MYC-mediated glycolysis in CRC cells. In addition, the transcription of LINRIS could be inhibited by GATA3 in CRC cells. In vivo experiments showed that the inhibition of LINRIS suppressed the proliferation of tumors in orthotopic models and in patient-derived xenograft (PDX) models. CONCLUSION: LINRIS is an independent prognostic biomarker for CRC. The LINRIS-IGF2BP2-MYC axis promotes the progression of CRC and is a promising therapeutic target.

5.
Food Funct ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31789332

RESUMO

Hyperuricemia (HUA) is a metabolic disorder that occurs due to the overproduction or under-excretion of uric acid (UA) and is directly linked to the development of many life-threatening diseases. There is a growing interest among many researchers regarding how to overcome the encumbrance of HUA because conventional drugs are associated with multiple side effects. Thus, the present project has been designed to utilize flavonoids and chlorogenic acid-enriched stevia residue extract (STVRE) to combat HUA. The results show that supplementation with STVRE (200 and 400 mg per kg bw) inhibits the XOD enzyme in serum, duodenum, jejunum, and ileum tissues. Moreover, UA levels in the STVRE groups were also significantly (p < 0.05) decreased in serum, duodenum, jejunum, and ileum tissues and juices. STVRE also improved the intestinal morphology and oxidative biomarkers in duodenum, jejunum, and ileum tissues. Protein and mRNA expressions of ABCG2 were upregulated, whereas GLUT9 was downregulated in the STVRE-treated groups as compared with the model control group. The supplementation of STVRE significantly attenuated hyperuricemia and oxidative stress, upregulated ABCG2 and downregulated GLUT9 (protein and mRNA) expression in hyperuricemic mice. The results of our study revealed that the by-product of stevia has the potential to combat hyperuricemia, and can be used as a functional ingredient in the development of nutraceutical products.

6.
J Nat Prod ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31799840

RESUMO

A new cyclic peptide photoditritide (1), containing two rare amino acid d-homoarginine residues, was isolated from Photorhabdus temperata Meg1 after the nonribosomal peptide synthetase encoding gene pdtS was activated via promoter exchange. The structure of 1 was elucidated by HR-MS and NMR experiments. The absolute configurations of amino acids were determined according to the advanced Marfey's method after hydrolysis of 1. Bioactivity testing of 1 revealed potent antimicrobial activity against Micrococcus luteus with an MIC value of 3.0 µM and weak antiprotozoal activity against Trypanosoma brucei rhodesiense with an IC50 value of 13 µM. Additionally, the biosynthetic pathway of 1 was also proposed.

7.
Cogn Behav Neurol ; 32(4): 217-224, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31800482

RESUMO

BACKGROUND: The role(s) of inflammation in obesity-associated cognitive decline in overweight or obese populations is not completely understood. OBJECTIVE: To investigate the profile of plasma inflammatory cytokines in overweight and obese Chinese individuals and to assess the relationship between inflammation and cognitive function. METHODS: We evaluated the cognitive domains of 282 Chinese adults, aged 35 to 64 years, using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). The participants were classified into three groups according to their body mass index. Inflammatory cytokines were determined by immune turbidimetric analysis and enzyme-linked immunosorbent assay. Data were analyzed using covariance and partial correlation analyses after adjusting for gender, age, education level, hypertension, and hyperlipemia. RESULTS: The total MoCA scores of the overweight and obese groups were significantly lower than that of the control group. The obese group displayed a significantly higher level of tumor necrosis factor-α than the overweight and control groups and a significantly higher level of transforming growth factor-ß than the control group. The overweight group displayed a significantly higher interleukin-4 level than the control and obese groups. After adjusting for confounding factors, however, we found no significant correlation between the level of plasma inflammatory cytokines and MMSE or MoCA total score. CONCLUSIONS: Compared to normal-weight Chinese participants, overweight and obese Chinese participants revealed significant differences in their inflammatory cytokines profile; however, the inflammatory cytokine levels did not correlate with the significantly lower cognitive scores observed in the overweight and obese groups.

8.
Front Immunol ; 10: 2408, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681297

RESUMO

Astrocyte-mediated inflammation and oxidative stress elicit cerebral ischemia-reperfusion (IR) injury after stroke. Nuclear factor (NF)-κB activates astrocytes and generates pro-inflammatory factors. The purpose of the present study is to elucidate the effect of pterostilbene (PTE, a natural stilbene) on astrocytic inflammation and neuronal oxidative injury following cerebral ischemia-reperfusion injury. A middle cerebral artery occlusion-reperfusion (MCAO/R) mouse model and HT22/U251 co-culture model subjected to oxygen-glucose deprivation and re-introduction (OGD/R) were employed, with or without PTE treatment. The data showed that PTE delivery immediately after reperfusion, at 1 h after occlusion, decreased infarct volume, brain edema, and neuronal apoptosis and improved long-term neurological function. PTE decreased oxidation (i.e., production of reactive oxygen species, malondialdehyde) and inflammatory mediators (tumor necrosis factor-α, interleukin-1ß, and interleukin-6) and increased anti-oxidative enzyme activities (i.e., of superoxide dismutase, glutathione peroxidase), by inhibiting phosphorylation and nuclear translocation of NF-κB. In conclusion, PTE attenuated astrocyte-mediated inflammation and oxidative injury following IR via NF-κB inhibition. Overall, PTE is a promising neuroprotective agent.

9.
Curr Pain Headache Rep ; 23(11): 86, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31707499

RESUMO

PURPOSE OF REVIEW: Many studies have demonstrated that discogenic low back pain is the most common type of chronic low back pain (CLBP), one of the major causes of disability, and has a major socioeconomic impact. Our aim is to review present therapeutic interventions for discogenic low back pain. RECENT FINDINGS: There are a multitude of treatments used in clinical practice to treat CLBP, but there is continued debate and lack of consensus among clinicians and the policy makers as to which modality is the best approach. Based on controlled evaluations, lumbar intervertebral discs have been shown to be the source of chronic back pain without disc herniation in 26 to 39% of patients. Treatment modalities include noninvasive treatments such as drug therapy, multiple physical modalities, and multidisciplinary biopsychosocial rehabilitation; interventional modalities such as intradiscal therapies and epidural injections; and regenerative modalities with disc injections of various solutions; and, finally, surgical approaches such as fusion and artificial disc replacement, all of which are accompanied by significant discussion, limited evidence, and lack of consensus. The results of this evaluation show that the evidence for drug therapy in chronic discogenic low back pain is limited; for multidisciplinary biopsychosocial rehabilitation, it is moderate; and for multiple physical and behavioral therapies, the evidence is limited. For intradiscal therapies, it is poor; for epidural injections, it is moderate; and for regenerative therapies, evidence levels of 3 to 4. The evidence for surgical fusions and disc replacement is similar, without superiority when compared with multidisciplinary biopsychosocial rehabilitation, well-designed physical therapy, or epidural injections.

10.
Cardiovasc Res ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31693092

RESUMO

AIMS: Conventional Fractional Flow Reserve (FFR) is measured invasively using a coronary guidewire equipped with a pressure sensor. A non-invasive derived FFR would eliminate risk of coronary injury, minimize technical limitations and potentially increase adoption. We aimed to evaluate the diagnostic performance of a computational pressure-flow dynamics (CPFD) derived FFR (caFFR), applied to coronary angiography, compared to invasive FFR. METHODS AND RESULTS: The FLASH FFR study was a prospective, multicenter, single-arm study conducted at six centers in China. Eligible patients had native coronary artery target lesions with visually estimated diameter stenosis of 30-90% and diagnosis of stable or unstable angina pectoris. Using computational pressure-fluid dynamics, in conjunction with TIMI frame count, applied to coronary angiography, caFFR was measured online in real-time and compared blind to conventional invasive FFR by an independent core laboratory. The primary endpoint was the agreement between caFFR and FFR, with a pre-specified performance goal of 84%. Between June and December 2018 matched caFFR and FFR measurements were performed in 328 coronary arteries. Total operational time for caFFR was 4.54±1.48 minutes. caFFR was highly correlated to FFR (R = 0.89, P=0.76) with a mean bias of -0.002±0.049 (95% limits of agreement -0.098 to 0.093). The diagnostic performance of caFFR versus FFR was diagnostic accuracy 95.7%, sensitivity 90.4%, specificity 98.6%, positive predictive value 97.2%, negative predictive value 95.0% and area under the receiver operating characteristic curve of 0.979. CONCLUSIONS: Using wire-based FFR as the reference, caFFR has high accuracy, sensitivity and specificity. caFFR could eliminate the need of a pressure wire, technical error and potentially increase adoption of physiological assessment of coronary artery stenosis severity. CLINICAL TRIAL REGISTRATION: URL: http://www.chictr.org.cn Unique Identifier: ChiCTR1800019522.

11.
Mol Med Rep ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31746398

RESUMO

Connective tissue growth factor (CTGF) is a possible key determinant of progressive fibrosis. Nanotechnology has been considered as a potential tool for developing novel drug delivery systems for various diseases, including liver fibrosis. The present study aimed to investigate the potential antifibrotic activity of CTGF small interfering RNA (siRNA) mediated by polyethyleneimine (PEI)­functionalized magnetic iron oxide (Fe3O4) nanoparticles (NPs) in LX­2 cells. PEI­Fe3O4/siRNA complexes were synthesized to facilitate siRNA delivery and were transfected into LX­2 cells. Laser confocal microscopy was employed to investigate the cell uptake of PEI­Fe3O4/siRNA complexes. Reverse transcription­quantitative PCR (RT­qPCR) and western blotting were used to verify the effect of gene silencing. The results showed that siRNA­loaded PEI­Fe3O4 exhibited low cytotoxicity. The transfection efficiency of PEI­Fe3O4/siRNA reached 73.8%, and RT­qPCR and western blotting demonstrated effective gene silencing. These results indicated that CTGF siRNA delivered by PEI­Fe3O4 NPs significantly reduces CTGF expression and collagen production in activated LX­2 cells, providing a basis for future in vivo studies.

12.
BMC Neurol ; 19(1): 291, 2019 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-31735164

RESUMO

BACKGROUND: Mutations of cyclooxygenase gene (COX gene) may increase the susceptibility of ischemic stroke. We investigated five variants (rs5788, rs1330344, rs3842788, rs20417, and rs689466) of two COX genes in order to explaining the association between these polymorphisms and we also investigated the association between these variants and ischemic stroke risk to determine whether gene-gene interaction between these genes increases the susceptibility of ischemic stroke or its subtypes. METHODS: A total of 1981 study subjects (1078 cases and 903 control subjects) were recruited. The interaction of multiple factors was investigated using Multifactor Dimensionality Reduction. The additive effect of single nucleotide polymorphisms on ischemic stroke or its subtypes were analyzed by multiple factor logistic regression. RESULTS: At COX-1(rs1330344), AA genotype carriers had a lower susceptibility of ischemic stroke (OR = 0.657, 95%CI = 0.437-0.988, P = 0.044), and A allele carriers had a lower susceptibility of ischemic stroke (OR = 0.812, 95%CI = 0.657-0.978, P = 0.029). At COX-1(rs3842788), AA genotype carriers had a higher susceptibility of ischemic stroke (OR = 5.203, 95% CI = 1.519-5.159, P = 0.016). At COX-2 (rs689466), AA genotype carriers had a higher susceptibility of large-artery atherosclerosis (OR = 1.404, 95% CI = 1.019-1.934, P = 0.038). COX-1(rs1330344, rs3842788) and COX-2 rs689466 interacted in SVO, but had no additive effect with ischemic stroke and other subtypes. CONCLUSIONS: At rs1330344, AA genotype may reduce the susceptibility of ischemic stroke. At rs3842788, AA genotype may increase the susceptibility of ischemic stroke. At rs689466, AA genotype may increase the susceptibility of large-artery atherosclerosis (LAA). COX - 1(rs1330344, rs3842788) and COX-2 rs689466 interacted in small vessel occlusion (SVO), but had no additive effect with ischemic stroke and other subtypes.

13.
Bioresour Technol ; : 122409, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31740246

RESUMO

In this study, the growth and lipid accumulation of Scenedesmus sp. using different nanoparticles and light sources were investigated. Xenon lamp can produce a broad illumination spectrum, and exhibited better performance than light-emitting diode. SiC and g-C3N4 nanoparticles improved the biomass and lipid accumulation, whereas TiO2 and TiC nanoparticles had inhibitory influence on microalgae. Lipid production can be improved by oxidative stress produced by combination of nanoparticles and xenon lamp irradiation. At the optimal SiC nanoparticles concentration of 150 mg L-1 and photoperiod of 6:18 h, the maximum biomass concentration and total lipid content reached 3.18 g L-1 and 40.26%, respectively. The addition of SiC nanoparticles could promote the substrate utilization rate and induce stress condition, thereby enhancing the activity of acetyl-CoA carboxylase and lipid biosynthesis. This research shows that SiC nanoparticles addition combined with xenon lamp illumination is a promising strategy to promote microalgal growth and lipid accumulation.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31674084

RESUMO

Excessive protein levels in diets result in incomplete digestion of nitrogenous nutrients that are excreted from the body, causing environment pollution. Alpha-ketoglutarate (AKG) has been reported to decrease dietary protein levels, promote intestinal health in piglets and reduce environmental pollution. However, the underlying mechanisms of AKG are largely unknown. The objective of this study was to determine the effects of low-protein diet supplementation of AKG on the growth performance, nitrogen metabolism, relative expression of amino acid transporter genes and mTOR signalling pathway of skeletal muscle in piglets. Forty-eight piglets with an initial weight of 11.53 ± 0.04 kg were randomly divided into four groups. Each group had four replicates, and each replicate had three pigs. A low-protein (LP) diet (crude protein was 14.96%) served as the control without AKG, while 0.5%, 1.0% and 1.5% AKG were added to the LP diet for the other experimental groups. The trial period lasted for 28 days. Compared with the LP group, the LP + 1.0%A and LP + 1.5%A groups increased the growth performance (p < .05);increased the mRNA levels of amino acid transporters in the duodenum, anterior jejunum and posterior jejunum (p < .05); and reduced faecal nitrogen and urine nitrogen emissions (p < .05). They also showed greater mRNA levels and phosphorylated protein levels for S6 kinase beta (S6K) (p < .05), mammalian target of rapamycin (mTOR) (p < .05) and 4E-binding protein 1 (4EBP1) (p < .05) in skeletal muscle. An LP diet supplemented with AKG activated the mTOR signalling and promoted the ability of the small intestine to absorb protein, thereby increasing protein deposition. Taken together, an LP diet supplemented with AKG provides a theoretical basis for the promotion and application of AKG in piglet production.

15.
Appl Opt ; 58(27): 7451-7457, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31674395

RESUMO

The Yb3+-Er3+ and Yb3+-Ho3+ co-doped Y6WO12 (YWO) luminescent materials were synthesized successfully using the solid-state reaction method, and their phase purity, upconversion (UC) spectra, and optical temperature sensing properties were studied. Upon 980 nm excitation, the dominant emission peak around 660 nm is found in the YWO:Yb3+,Er3+ sample, which could be attributed to the Er3+F49/2-I415/2 electronic transition. Two green emission peaks of Er3+ appear in the range from 515-575 nm. For the YWO:Yb3+,Ho3+ phosphor, there are three emission peaks found at 548, 667, and 758 nm, which can be ascribed to the (F45,S52)-I58, F55-I58, and (F45,S52)-I57 transitions of Ho3+, respectively. By studying the emission intensity dependence of the pumping power, the result suggests that the two-photon process is involved for all the above emissions. In the temperature range of 293-553 K, the temperature sensing behavior of the typical YWO:10%Yb3+,1%Er3+ and YWO:10%Yb3+,1%Ho3+ phosphors was investigated in detail, and the results have been shown by using the fluorescence intensity ratio technique and decay curves. The above investigations indicate that the present UC phosphors could be promising phosphor materials for temperature sensor.

16.
J Cell Mol Med ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31670476

RESUMO

Epicardial adipose tissue (EAT) is a metabolically active visceral fat depot closely linked to the pathogenesis of heart failure (HF). But the molecular signatures related to the mechanism of HF have not been systematically explored. Here, we present comprehensive proteomic analysis of EAT in HF patients and non-HF patients as controls. A total of 771 proteins were identified in liquid chromatography-tandem mass spectrometry experiments. Amongst them, 17 increased in abundance in HF and seven decreased. They were involved in HF-related processes including inflammation and oxidative stress response and lipid metabolism. Of these proteins, serine proteinase inhibitor A3 (Serpina3) levels in EAT were highly up-regulated in HF, with HF/non-HF ratio of 4.63 (P = .0047). Gene expression of Serpina3 via quantitative polymerase chain reaction was significantly increased in the HF group. ELISA analysis confirmed a significant increase in circulating plasma Serpina3 levels in the HF group (P = .004). In summary, for the first time, we describe that parts of EAT proteome may be reactive and work as modulators of HF. Our profiling provides a comprehensive basis for linking EAT with pathogenesis of HF. Understanding the role of EAT may offer new insights into the treatment of HF.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31694758

RESUMO

Ebola virus (EBOV) is a zoonotic pathogen, the infection often results in severe, potentially fatal, systematic disease in human and nonhuman primates. VP35, an essential viral RNA-dependent RNA polymerase cofactor, is indispensable for Ebola viral replication and host innate immune escape. In this study, VP35 was demonstrated to be phosphorylated at Serine/Threonine by immunoblotting, and the major phosphorylation sites was S187, S205, T206, S208 and S317 as revealed by LC-MS/MS. By an EBOV minigenomic system, EBOV minigenome replication was shown to be significantly inhibited by the phosphorylation-defective mutant, VP35 S187A, but was potentiated by the phosphorylation mimic mutant VP35 S187D. Together, our findings demonstrate that EBOV VP35 is phosphorylated on multiple residues in host cells, especially on S187, which may contribute to efficient viral genomic replication and viral proliferation.

18.
Eur J Med Chem ; : 111841, 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31708183

RESUMO

Influenza A neuraminidase plays an indispensable role in the process of replication and transmission of influenza, so the neuraminidase inhibition can prevent the reproduction of the viruses therefore achieve the effect of treatment of influenza. However, drug resistance of neuraminidase inhibitors such as oseltamivir highlights the need to develop novel structural neuraminidase inhibitors. Here we explored a series of oseltamivir derivatives bearing pyridyl group. Among them, compound 23b exhibiting potent inhibitory activity against neuraminidase from H5N1 subtype was comparable to oseltamivir carboxylate. Cytopathic effect inhibition assay in MDCK cells indicated that compound 23b exerted powerful inhibitions on influenza viruses. And compound 23b were nontoxic to MDCK cells. Meanwhile, compound 23b showed high stability towards rat liver microsomes, human liver microsomes and human plasma. This research enriched the structural type of neuraminidase inhibitors.

19.
Cell Rep ; 29(6): 1568-1578.e4, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31693896

RESUMO

The size of dendrite arbors shapes their function and differs vastly between neuron types. The signals that control dendritic arbor size remain obscure. Here, we find that in the retina, starburst amacrine cells (SACs) and rod bipolar cells (RBCs) express the homophilic cell-surface protein AMIGO2. In Amigo2 knockout (KO) mice, SAC and RBC dendrites expand while arbors of other retinal neurons remain stable. SAC dendrites are divided into a central input region and a peripheral output region that provides asymmetric inhibition to direction-selective ganglion cells (DSGCs). Input and output compartments scale precisely with increased arbor size in Amigo2 KO mice, and SAC dendrites maintain asymmetric connectivity with DSGCs. Increased coverage of SAC dendrites is accompanied by increased direction selectivity of DSGCs without changes to other ganglion cells. Our results identify AMIGO2 as a cell-type-specific dendritic scaling factor and link dendrite size and coverage to visual feature detection.

20.
Anal Chem ; 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31710814

RESUMO

Exploration of simple and universal methods to quantitatively measure nanoparticle (NP)-protein interaction is of great importance. In this work, pulsed streaming potential (SP) measurement has been used to evaluate the interaction between NPs and proteins within microchannels. Graphene oxide (GO) and SiO2 NPs were selected to represent two kinds of NPs. Lysozyme and common blood proteins, including albumin V, γ-globulins, and fibrinogen, were used as model proteins. The linear relationship between the initial adsorption rate (S = dEr/dt) and the concentration of proteins was observed. Combined with the Hill equation, the microscopic dissociation constant (KD) and the Hill coefficient (n) between NPs and proteins were calculated based on the relationship between S and the concentration of each protein. The concentration of free proteins which have not interacted with the NPs in the NPs-protein mixture could also be measured. The influence of pH, conductivity, and ionic strengths of the incubation buffer on the interaction between GO and lysozyme was evaluated based on the constant KD. The interaction intensity between NPs and proteins was defined as charge neutralization efficiency QC, which could be calculated from the value of S. It takes only 150 s to get the whole set of data under the optimized experiment parameters. The measurement solely depends on the surface charge, no intrinsic fluorescence is required for either the NPs or the proteins, and no labeling or immobilization process is involved as well.

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