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1.
Artigo em Inglês | MEDLINE | ID: mdl-31486711

RESUMO

The separation of plasma from blood cells is critical for the accuracy of blood tests because cellular fractions can create discrepancies in analysis. The most common method to separate blood cells from the liquid part of the blood is centrifugation, which is not always applicable in resource-constrained areas and countries. In this study, we describe the generation of monoclonal antibodies (mAbs) against glycophorin A (GPA) of human erythrocytes. BALB/c mice were immunized with human erythrocytes followed by purified GPA. The splenocytes of the immunized mice were fused with Sp2/0 myeloma cells by hybridoma technique. Hybridoma clones were screened by hemagglutination assay and enzyme-linked immunosorbent assay (ELISA). Six hybridoma clones were obtained and subcloned. The characterization of the purified mAbs demonstrates that they are able to bind and retain erythrocytes in hemagglutination assay. Furthermore, one of the mAbs 1A9 recognizes purified GPA in ELISA, whereas the other mAb 1G7 is able to immunoprecipitate GPA from human erythrocyte lysates, and a band of 38 kDa is detected. In conclusion, the anti-GPA mAbs are useful tools in developing a quick and easy way to separate blood plasma from whole blood for clinical tests, and in developing bi-specific antibodies for other clinical applications.

2.
J Cell Physiol ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31489637

RESUMO

Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a member of the immunoglobulin superfamily and is expressed by hematopoietic and endothelial cells (ECs). Recent studies have shown that PECAM-1 plays a crucial role in promoting the development of the EC inflammatory response in the context of disturbed flow. However, the mechanistic pathways that control PECAM-1 protein stability remain largely unclear. Here, we identified PECAM-1 as a novel substrate of the APC/Cdh1 E3 ubiquitin ligase. Specifically, lentivirus-mediated Cdh1 depletion stabilized PECAM-1 in ECs. Conversely, overexpression of Cdh1 destabilized PECAM-1. The proteasome inhibitor MG132 blocked Cdh1-mediated PECAM-1 degradation. In addition, Cdh1 promoted K48-linked polyubiquitination of PECAM-1 in a destruction box-dependent manner. Furthermore, we demonstrated that compared with pulsatile shear stress (PS), oscillatory shear stress decreased the expression of Cdh1 and the ubiquitination of PECAM-1, therefore stabilizing PECAM-1 to promote inflammation in ECs. Hence, our study revealed a novel mechanism by which fluid flow patterns regulate EC homeostasis via Cdh1-dependent ubiquitination and subsequent degradation of PECAM-1.

4.
FEBS J ; 2019 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-31423749

RESUMO

The E3 ubiquitin ligase neural precursor cell-expressed developmentally down-regulated protein 4 (NEDD4) plays a crucial role in governing a number of signaling pathways, including insulin and autophagy signaling. However, the molecular mechanism by which NEDD4 gene is transcriptionally regulated has not been fully elucidated. Here, we reported that NEDD4 mRNA and protein levels were increased by peroxisome proliferator-activated receptor-γ (PPARγ) in HepG2 hepatocytes. PPARγ antagonist GW9662 abolished thiazolidinedione (TZD)-induced NEDD4 expression. ChIP and luciferase reporter assays showed that PPARγ directly bound to the potential PPAR-responsive elements (PPREs) within the promoter region of the human NEDD4 gene. In addition, TZDs increased Akt phosphorylation and glucose uptake, which were abrogated through NEDD4 depletion. Furthermore, we showed that NEDD4-mediated autophagy induction and Akt phosphorylation were suppressed by oleic acid and high glucose treatment, activation of PPARγ successfully prevented this suppression. In conclusion, these results suggest that PPARγ plays a novel role in linking glucose metabolism and protein homeostasis through NEDD4-mediated effects on the autophagy machinery.

5.
Stat Methods Med Res ; : 962280219870836, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31456486

RESUMO

This paper concerns estimation of subgroup treatment effects with observational data. Existing propensity score methods are mostly developed for estimating overall treatment effect. Although the true propensity scores balance covariates in any subpopulations, the estimated propensity scores may result in severe imbalance in subgroup samples. Indeed, subgroup analysis amplifies a bias-variance tradeoff, whereby increasing complexity of the propensity score model may help to achieve covariate balance within subgroups, but it also increases variance. We propose a new method, the subgroup balancing propensity score, to ensure good subgroup balance as well as to control the variance inflation. For each subgroup, the subgroup balancing propensity score chooses to use either the overall sample or the subgroup (sub)sample to estimate the propensity scores for the units within that subgroup, in order to optimize a criterion accounting for a set of covariate-balancing moment conditions for both the overall sample and the subgroup samples. We develop two versions of subgroup balancing propensity score corresponding to matching and weighting, respectively. We devise a stochastic search algorithm to estimate the subgroup balancing propensity score when the number of subgroups is large. We demonstrate through simulations that the subgroup balancing propensity score improves the performance of propensity score methods in estimating subgroup treatment effects. We apply the subgroup balancing propensity score method to the Italy Survey of Household Income and Wealth (SHIW) to estimate the causal effects of having debit card on household consumption for different income groups.

6.
Int J Mol Med ; 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31364746

RESUMO

Mycobacterium tuberculosis (M. tb) is a highly successful pathogen that has co­existed with humans for 1,000's of years. As the cornerstone of the immune system, macrophages are a key part of innate immunity. They ingest and degrade foreign substances including aging cells and microorganisms, coordinate the inflammatory process, and are the first line of defense against M. tb infection. Recent advances in cellular mycobacteriology have indicated that M. tb uses an remarkably complex strategy to disrupt macrophage function, in order to counteract the antimicrobial mechanisms of the innate and adaptive immune responses, thereby achieving immune escape. With the popularity of microarray technology, a variety of public platforms have provided a variety of gene expression data associated with physiological and disease conditions. Meta­analysis can systematically and quantitatively analyze multiple independent data concerning the same disease, greatly improving the statistical significance and credibility of the gene expression data analysis performed. In the present study, 6 microarray expression datasets of human acute monocytic leukemia THP­1 cell line infected by M. tb H37Rv strain were collected from the GEO database. A total of 4 high­quality datasets were identified using meta­analysis methods in R language, and 306 differentially expressed genes with statistical significance were obtained. Then, a protein­protein interaction (PPI) network of these differentially expressed genes was constructed on the Search Tool for the Retrieval of Interacting Genes/Proteins Database online tool and visualized by Cytoscape v. 3.6.1 software. Using CentiScape and MCODE plugin in the Cytoscape software to mine the functional modules associated with M. tb infection process, 32 characteristic genes were identified. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis was performed on the 32 characteristic genes, and it was demonstrated that these genes were primarily associated with the type I interferon (IFN) pathway. In the established model of THP­1­derived macrophages infected by M. tb, the actual differential expression levels of IFN­stimulated gene 15 (ISG15), 2'­5­oligoadenylate synthetase like (OASL), IFN regulatory factor 7 (IRF7) and DExD/H­box helicase 58 (DDX58), the first 4 genes of the 32 characteristic genes, were verified by reverse transcription quantitative polymerase chain reaction. The results were consistent with the results of microarray analysis. The association between ISG15, OASL and IRF7 and TB infection was also verified. Although a number of studies have identified that the type I IFN pathway may assist M. tb to achieve immune escape, the present study used a meta­analysis of microarray data and PPI network analysis to examine some of the novel genes identified in the IFN pathway. The results furthered the understanding of the molecular mechanisms of the TB immune response and provided a novel perspective for future therapeutic goals.

7.
ACS Appl Mater Interfaces ; 11(35): 31649-31660, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31407880

RESUMO

Synergistic therapeutic strategies for bacterial infection have attracted extensive attentions owing to their enhanced therapeutic effects and less adverse effects compared with monotherapy. Herein, we report a novel synergistic antibacterial platform that integrates the nanocatalytic antibacterial therapy and photothermal therapy (PTT) by hemoglobin-functionalized copper ferrite nanoparticles (Hb-CFNPs). In the presence of a low concentration of hydrogen peroxide (H2O2), the excellent Fenton and Fenton-like reaction activity of Hb-CFNPs can effectively catalyze the decomposition of H2O2 to produce hydroxyl radicals (·OH), rendering an increase in the permeability of the bacterial cell membrane and the sensitivity to heat. With the assistance of NIR irradiation, hyperthermia generated by Hb-CFNPs can induce the death of the damaged bacteria. Additionally, owing to the outstanding magnetic property of Hb-CFNPs, it can improve the photothermal efficiency by about 20 times via magnetic enrichment, which facilitates to realize excellent bactericidal efficacy at a very low experimental dose (20 µg/mL). In vitro antibacterial experiment shows that this synergistic antibacterial strategy has a broad-spectrum antibacterial property against Gram-negative Escherichia coli (E. coli, 100%) and Gram-positive Staphylococcus aureus (S. aureus, 96.4%). More importantly, in vivo S. aureus-infected abscess treatment studies indicate that Hb-CFNPs can serve as an antibacterial candidate with negligible toxicity to realize synergistic treatment of bacterial infections through catalytic and photothermal effects. Accordingly, this study proposes a novel, high-efficiency, and multifunctional therapeutic system for the treatment of bacterial infection, which will open up a new avenue for the design of synergistic antibacterial systems in the future.

8.
Stud Health Technol Inform ; 264: 1835-1836, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438367

RESUMO

Patients with olfactory disorders are often encountered with a complex workflow and unsatisfied results. This article explores an informatics application to manage olfactory disorders with clinical decision support. Evidence from PubMed was used to analyze and extract the workflow, according to the "five rights" CDS framework. Five focus points and corresponding tips were identified. This work provides disease analysis and life guidance for prediction of the occurrence of more serious diseases.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Idoso , Humanos , Transtornos do Olfato , Fluxo de Trabalho
9.
Opt Lett ; 44(17): 4235-4238, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31465370

RESUMO

In this Letter, a fiber-wireless integration system at Ka-band adopting heterodyne coherent detection is proposed and experimentally demonstrated. Optical I/Q up-conversion is realized with a low-cost dual-drive Mach-Zehnder modulator (DD-MZM) instead of the traditional I/Q nested MZM. To avoid non-convergence during constant-modulus-algorithm-based equalization, DC elimination is applied to suppress the ultra-high peak in the frequency domain after frequency down-conversion and symbol-phase-average-processing-based coarse phase noise estimation. Using DD-MZM for optical I/Q modulation, transmission, and reception of single polarization, 20-Gbit/s quadrature phase shift keying (QPSK) over 40-km single-mode fiber (SMF) and 5-m free space at Ka-band is demonstrated.

10.
Cell Prolif ; : e12687, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31468594

RESUMO

OBJECTIVES: As one of the most life-threatening malignancies, gastric cancer is the third contributor of cancer mortalities globally. Increasing studies have proven the regulatory roles of lncRNAs in the development of diverse malignant tumours. But little is known about its function and molecular mechanism in gastric carcinoma. MATERIALS AND METHODS: RT-qPCR was performed to measure the expression pattern of LOXL1-AS1 in gastric cancer. To ascertain its definite role, CCK-8, EdU, Western blot, transwell and sphere formation assays were adopted. RNA pull-down, RIP, ChIP and luciferase reporter assays were carried out to investigate the molecular mechanism of LOXL1-AS1 in gastric carcinoma. RESULTS: LOXL1-AS1 was highly expressed in tissues and cells of gastric cancer. The upregulation of LOXL1-AS1 predicted poor prognosis in gastric carcinoma. Our findings demonstrated that LOXL1-AS1 accelerated the deterioration of gastric cancer by inducing cell proliferation, migration, EMT and stemness. Moreover, the expression of USF1 in gastric cancer was higher than in normal control and LOXL1-AS1 negatively modulated USF1. Functionally, LOXL1-AS1 acted as a ceRNA to upregulate USF1 via sponging miR-708-5p. Besides, we confirmed USF1 promoted the transcription of stemness marker SOX2. Rescue experiments testified the stimulative role of LOXL1-AS1/miR-708-5p/USF1 pathway in gastric cancer progression. It was also validated that LOXL1-AS1 facilitated cell growth of gastric carcinoma in vivo. CONCLUSIONS: Our study unravelled that LOXL1-AS1/miR-708-5p/USF1 pathway contributed to the development of gastric cancer.

11.
J Immunother Cancer ; 7(1): 201, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31366386

RESUMO

BACKGROUND: Interleukin(IL)-30/IL-27p28 production by Prostate Cancer (PC) Stem-Like Cells (SLCs) has proven, in murine models, to be critical to tumor onset and progression. In PC patients, IL-30 expression by leukocytes infiltrating PC and draining lymph nodes correlates with advanced disease grade and stage. Here, we set out to dissect the role of host immune cell-derived IL-30 in PC growth and patient outcome. METHODS: PC-SLCs were implanted in wild type (WT) and IL-30 conditional knockout (IL-30KO) mice. Histopathological and cytofluorimetric analyses of murine tumors and lymphoid tissues prompted analyses of patients' PC samples and follow-ups. RESULTS: Implantation of PC-SLCs in IL-30KO mice, gave rise to slow growing tumors characterized by apoptotic events associated with CD4+T lymphocyte infiltrates and lack of CD4+Foxp3+ T regulatory cells (Tregs). IL-30 knockdown in PC-SLCs reduced cancer cell proliferation, vascularization and intra-tumoral Indoleamine 2,3-Dioxygenase (IDO)+CD11b+Gr-1+ myeloid-derived cells (MDCs) and led to a significant delay in tumor growth and increase in survival. IL-30-silenced tumors developed in IL-30KO mice, IL-30-/-tumors, lacked vascular supply and displayed frequent apoptotic cancer cells entrapped by perforin+TRAIL+CD3+Tlymphocytes, most of which had a CD4+T phenotype, whereas IL-10+TGFß+Foxp3+Tregs were lacking. IL-30 silencing in PC-SLCs prevented lung metastasis in 73% of tumor-bearing WT mice and up to 80% in tumor-bearing IL-30KO mice. In patients with high-grade and locally advanced PC, those with IL-30-/-tumors, showed distinct intra-tumoral cytotoxic granule-associated RNA binding protein (TIA-1)+CD4+Tlymphocyte infiltrate, rare Foxp3+Tregs and a lower biochemical recurrence rate compared to patients with IL-30+/+tumors in which IL-30 is expressed in both tumor cells and infiltrating leukocytes. CONCLUSION: The lack of host leukocyte-derived IL-30 inhibits Tregs expansion, promotes intra-tumoral infiltration of CD4+T lymphocytes and cancer cell apoptosis. Concomitant lack of MDC influx, obtained by IL-30 silencing in PC-SLCs, boosts cytotoxic T lymphocyte activation and cancer cell apoptosis resulting in a synergistic tumor suppression with the prospective benefit of better survival for patients with advanced disease.

12.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 33(8): 991-995, 2019 Aug 15.
Artigo em Chinês | MEDLINE | ID: mdl-31407559

RESUMO

Objective: To investigate the feasibility and effectiveness of modified replanting posterior ligament complex (PLC) applying piezoelectric osteotomy in the treatment of primary benign tumors in thoracic spinal canal. Methods: The clinical data of 38 patients with primary benign tumors in thoracic spinal canal between March 2014 and March 2016 were retrospectively analyzed. There were 16 males and 22 females, aged from 21 to 72 years (mean, 47.1 years). The disease duration ranged from 6 to 57 months (mean, 32.6 months). Pathological examination showed 24 cases of schwannoma, 6 cases of meningioma, 4 cases of ependymoma, 2 cases of lipoma, and 2 cases of dermoid cyst. The lesions located in 18 cases of single segment, 15 cases of double segments, and 5 cases of three segments. The length of the tumors ranged from 0.7 to 6.5 cm. There were boundaries between the tumors and the spinal cord, cauda equina, and nerve roots. The preoperative Japanese Orthopaedic Association (JOA) score was 12.2±2.3 and the thoracic Cobb angle was (11.7±2.7)°. Modified PLC replantation and microsurgical resection were performed with piezoelectric osteotomy. Continuity of uniside supraspinal and interspinous ligaments were preserved during the operation. The PLC was exposed laterally. After removing the tumors under the microscope, the pedicled PLC was replanted in situ and fixed with bilateral micro-reconstruction titanium plate. X-ray film, CT, and MRI examinations were performed to observe spinal stability, spinal canal plasty, and tumor resection after operation. The effectiveness was evaluated by JOA score. Results: The operation time was 56-142 minutes (mean, 77.1 minutes). The intraoperative blood loss was 110-370 mL (mean, 217.2 mL). The tumors were removed completely and the incisions healed well. Three cases complicated with cerebrospinal fluid leakage, and there was no complications such as spinal cord injury and infection. All the 38 patients were followed up 24-28 months (mean, 27.2 months). There was no internal fixation loosening, malposition, or other related complications. At last follow-up, X-ray films showed no sign of kyphosis and instability. CT showed no displacement of vertebral lamina and reduction of secondary spinal canal volume, and vertebral lamina healed well. MRI showed no recurrence of tumors. At last follow-up, the thoracic Cobb angle was (12.3±4.1)°, showing no significant difference when compared with preoperative value ( t=0.753, P=0.456). JOA score increased to 23.7±3.8, showing significant difference when compared with preoperative value ( t=15.960, P=0.000). Among them, 14 cases were excellent, 18 were good, 6 were fair, and the excellent and good rate was 84.2%. Conclusion: Modified replanting PLC applying piezoelectric osteotomy and micro-reconstruction with titanium plate for the primary benign tumors in thoracic spinal canal can reconstruct the anatomy of the spinal canal, enable patients to recover daily activities quickly. It is an effective and safe treatment.

13.
Org Lett ; 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31418581

RESUMO

A general and mild method to prepare enantioenriched α-trifluoromethyl, α-stereogenic homoallylic amines is established. This reaction, which involves an Ir-catalyzed umpolung allylation of imines and a 2-aza-Cope rearrangement cascade, could yield both tetrasubstituted and trisubstituted stereocenters. This transformation employs readily available starting materials and displays broad substrate scope. The isolation and structural determination of reaction intermediates revealed factors critical for the efficiency and stereoselectivity of this transformation.

14.
J Med Genet ; 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31413119

RESUMO

BACKGROUND: Neuronal intranuclear inclusion disease (NIID) is a heterogenous neurodegenerative disorder named after its pathological features. It has long been considered a disease of genetic origin. Recently, the GGC repeated expansion in the 5'-untranslated region (5'UTR) of the NOTCH2NLC gene has been found in adult-onset NIID in Japanese individuals. This study was aimed to investigate the causative mutations of NIID in Chinese patients. METHODS: Fifteen patients with NIID were identified from five academic neurological centres. Biopsied skin samples were analysed by histological staining, immunostaining and electron microscopic observation. Whole-genome sequencing (WGS) and long-read sequencing (LRS) were initially performed in three patients with NIID. Repeat-primed PCR was conducted to confirm the genetic variations in the three patients and the other 12 cases. RESULTS: Our patients included 14 adult-onset patients and 1 juvenile-onset patient characterised by degeneration of multiple nervous systems. All patients were identified with intranuclear inclusions in the nuclei of fibroblasts, fat cells and ductal epithelial cells of sweat glands. The WGS failed to find any likely pathogenic variations for NIID. The LRS successfully identified that three patients with adult-onset NIID showed abnormalities of GGC expansion in 5'UTR of the NOTCH2NLC gene. The GGC repeated expansion was further confirmed by repeat-primed PCR in seven familial cases and eight sporadic cases. CONCLUSION: Our findings provided evidence that confirmed the GGC repeated expansion in the 5'UTR of the NOTCH2NLC gene is associated with the pathogenesis of NIID. Additionally, the GGC expansion was not only responsible for adult-onset patients, but also responsible for juvenile-onset patients.

15.
ACS Appl Mater Interfaces ; 11(36): 33515-33524, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31423760

RESUMO

In this work, a novel back contact interface engineering is developed for inverted planar perovskite solar cells, in which a tetrafluoroterephthalic acid (TFTPA) interlayer is inserted between CH3NH3PbI3 and PC61BM to strengthen the interface contact. Benefiting from the strong Coulombic interactions between positive electron-poor tetrafluoroterephthalate moieties and negative electron-rich fullerene molecules, as well as the coordinate effect between -COOH groups of TFTPA and Pb2+ ions of perovskites surface, a tightly jointing and defect-passivated CH3NH3PbI3/PC61BM interface is formed. The strengthened CH3NH3PbI3/PC61BM back contact can significantly facilitate electron transport and simultaneously diminish the charge accumulation and recombination. Therefore, power conversion efficiency (PCE) of the TFTPA device is up to 19.39%, whereas the hysteresis effect is weak, and the PCE is improved by 20.4% compared with the control device which does not have a TFTPA interlayer. Particularly, the moisture stability of the TFTPA device is greatly improved as compared to the control device. Our findings illustrate that the back contact interface engineering is an important and promising approach for inverted planar perovskite solar cells.

16.
Hum Gene Ther ; 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31373227

RESUMO

Safe delivery of CRISPR/Cas endonucleases remains one of the major barriers to the widespread application of in vivo genome editing. We previously reported the utility of adeno-associated virus (AAV)-mediated CRISPR/Cas genome editing in the retina; however, with this type of viral delivery system, active endonucleases will remain in the retina for an extended period, making genotoxicity a significant consideration in clinical applications. To address this issue, we have designed a self-destructing "kamikaze" CRISPR/Cas system that disrupts the Cas enzyme itself following expression. Four guide RNAs (sgRNAs) were initially designed to target Streptococcus pyogenes Cas9 (SpCas9) and after in situ validation, the selected sgRNAs were cloned into a dual AAV vector. One construct was used to deliver SpCas9 and the other delivered sgRNAs directed against SpCas9 and the target locus (yellow fluorescent protein, YFP), in the presence of mCherry. Both constructs were packaged into AAV2 vectors and intravitreally administered in C57BL/6 and Thy1-YFP transgenic mice. After 8 weeks the expression of SpCas9 and the efficacy of YFP gene disruption was quantified. A reduction of SpCas9 mRNA was found in retinas treated with AAV2-mediated-YFP/SpCas9 targeting CRISPR/Cas compared to those treated with YFP targeting CRISPR/Cas alone. We also show that AAV2-mediated delivery of YFP/SpCas9 targeting CRISPR/Cas significantly reduced the number of YFP fluorescent cells among mCherry-expressing cells (~85.5% reduction compared to LacZ/SpCas9 targeting CRISPR/Cas) in the transfected retina of Thy1-YFP transgenic mice. In conclusion, our data suggest that a self-destructive "kamikaze" CRISPR/Cas system can be used as a robust tool for genome editing in the retina, without compromising on-target efficiency.

17.
Curr Alzheimer Res ; 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31368873

RESUMO

BACKGROUND: Alzheimer's disease (AD) is characterized by the presence of extracellular amyloid-ß (Aß) plaques and intraneuronal neurofibrillary tangles assembled by the microtubule-associated protein tau. Increasing evidences demonstrated that tau pathology played an important role in AD progression. Resveratrol (RSV) has been previously proved to exert neuroprotective effect against AD by inhibiting Aß generation and Aß-induced neurocytotoxicity, while its effect on tau pathology is still unknown. METHOD: The effect of RSV on tau aggregation was measured by Thioflavin T fluorescence and Transmission electron microscope imaging; The effect of RSV on tau oligomer-induced cytotoxicity was assessed by MTT assay; The uptake of extracellular tau by N2a cells was determined by immunocytochemistry. 6-month-old male PS19 mice were treated with RSV or vehicle by oral administration (gavage) once a day for 5 weeks. The cognitive performance was determined using Morris water maze test, object recognition test and Y-maze test. The levels of phosphorylated-tau, gliosis, proinflammatory cytokines such as TNF-α and IL-1ß, and synaptic proteins including synaptophysin and PSD95 in the mouse brains were evaluated by immunoblotting, immunostaining and ELISA, respectively. RESULTS: RSV significantly inhibited tau aggregation and tau oligomer-induced cytotoxicity, and blocked the uptake of extracellular tau oligomers by N2a cells. When applied to PS19 mice, RSV treatment effectively rescued cognitive deficits, reduced the levels of phosphorylated tau, neuroinflammation and synapse loss in the brains of mice. CONCLUSION: These findings suggest that RSV has promising therapeutic potential for AD and other tauopathies.

18.
J Mater Chem B ; 7(30): 4620-4629, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31364679

RESUMO

A novel probe, 3-benzyl-2-(N-ethylcarbazole-3-vinyl)-benzothiazolium bromide (L), was synthesized and utilized for the specific detection of cyanide ions in neutral aqueous solution (HEPES buffer, pH 7.4). This probe displays a fast response through visible colorimetric and fluorogenic changes toward CN-, allowing for ratiometric sensing of cyanide in aqueous media. The ratiometric response is due to the breaking of the extensive π-conjugation and the intramolecular charge transfer (ICT) by the nucleophilic conjugation addition of cyanide to L, which is ascertained by NMR and ESI-MS analysis as well as density functional theory (DFT) calculations. The detection limit of CN- (3.39 × 10-7 M) is well below the limit recommended in the World Health Organization (WHO) guidelines for drinking water. Moreover, fluorescence co-localization studies demonstrate that L is a specific mitochondria-targeting fluorescent probe. As far as we are aware, compound L is the first mitochondria-targeting probe for cyanide detection and can be used for sensing CN- in living cells with dual channel ratiometric fluorescence imaging.

19.
Sci Total Environ ; 695: 133779, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31412302

RESUMO

Sea level rise is expected to increase inundation and saltwater intrusion into many tidal freshwater marshes and forests. Saltwater intrusion may be long-term, as with rising seas, or episodic, as with low river flow or storm surge. We applied continuous (press) and episodic (pulse) treatments of dilute seawater to replicate 2.5 × 2.5 m field plots for three years and measured soil attributes, including soil porewater, oxidation-reduction potential, soil carbon (C), and nitrogen (N) to investigate the effects of continuous and episodic saltwater intrusion and increased inundation on tidal freshwater marsh elemental cycling and soil processes. Continuous additions of dilute seawater resulted in increased porewater chloride, sulfate, sulfide, ammonium, and nitrate concentrations. Plots that received press additions also had lower soil oxidation-reduction potentials beginning in the second year. Episodic additions of dilute seawater during typical low flow conditions (Sept.-Oct.) resulted in transient increases in porewater chloride and sulfate that returned to baseline conditions once dosing ceased. Freshwater additions did not affect porewater inorganic N or soil C or N. Persistent saltwater intrusion in freshwater marshes alters the N cycle by releasing ammonium-N from sorption sites, increasing nitrification and severely reducing N storage in macrophyte biomass. Chronic saltwater intrusion, as is expected with rising seas, is likely to shift tidal freshwater marshes from a sink to a source of N whereas intermittent intrusion from drought may have no long term effect on N cycling.

20.
Stud Health Technol Inform ; 264: 228-232, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31437919

RESUMO

Meta-analysis, a systematic retrieval from literature databases is an essential and prevailing method for combining data from multiple studies. Unfortunately, few studies have examined its rigor, which affects its reproducibility of results. We identified 22 meta-analyses on cervical cancer in PubMed for examining the parameters defined by PRISMA, relating to the rigor of literature retrieval. We found that 16 literature databases were used, and EMBASE was a leading resource, accounting for the highest frequency (81.82%). About half (45.45%) of the meta-analyses presented a complete, reproducible search strategy for at least one database. The ratio of included to retrieved articles after redundancy removal was only 6.58%, indicating low precision due to unclear or unreported processes. Our work serves as an initial step to examine the planning and execution of meta-analysis. Future efforts need to enhance reliability on literature retrieval in meta-analysis and compliance to PRISMA.


Assuntos
Recursos em Saúde , Armazenamento e Recuperação da Informação , Reprodutibilidade dos Testes , Bases de Dados Factuais , PubMed
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