Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 327
Filtrar
1.
Sci Rep ; 10(1): 8187, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32424344

RESUMO

Insulin is a protein hormone that controls the metabolism of sugar, fat and protein via signal transduction in cells, influencing growth and developmental processes such as reproduction and ageing. From nematodes to fruit flies, rodents and other animals, glucose signalling mechanisms are highly conserved. Reproductive termites (queens and kings) exhibit an extraordinarily long lifespan relative to non-reproductive individuals such as workers, despite being generated from the same genome, thus providing a unique model for the investigation of longevity. The key reason for this molecular mechanism, however, remains unclear. To clarify the molecular mechanism underlying this phenomenon, we sequenced the transcriptomes of the primary kings (PKs), primary queens (PQs), male (WMs) and female (WFs) workers of the lower subterranean termite Reticulitermes chinensis. We performed RNA sequencing and identified 33 insulin signalling pathway-related genes in R. chinensis. RT-qPCR analyses revealed that EIF4E and RPS6 genes were highly expressed in WMs and WFs workers, while mTOR expression was lower in PKs and PQs than in WMs and WFs. PQs and PKs exhibited lower expression of akt2-a than female workers. As the highly conserved insulin signalling pathway can significantly prolong the healthspan and lifespan, so we infer that the insulin signalling pathway regulates ageing in the subterranean termite R. chinensis. Further studies are recommended to reveal the biological function of insulin signalling pathway-related genes in the survival of termites to provide new insights into biomolecular homeostasis maintenance and its relationship to remarkable longevity.

2.
Acta Radiol ; : 284185120920793, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32380911

RESUMO

BACKGROUND: Loss of swallow tail sign (STS) on iron-sensitive magnetic resonance imaging (MRI) has been recognized as an imaging feature in parkinsonism (PS). PURPOSE: To investigate the diagnostic and differential diagnostic value of STS scale on susceptibility map-weighted imaging (SMWI) in PS, including Parkinson's disease (PD), progressive supranuclear palsy syndrome (PSP), and multiple system atrophy (MSA), and to evaluate its correlation with disease severity. MATERIAL AND METHODS: Ninety-nine patients (55 PD, 29 PSP, and 15 MSA) and 47 healthy controls (HC) were prospectively recruited and scanned using quantitative susceptibility mapping (QSM). STS was visually assessed on SMWI derived from QSM. STS scale in the range of 0-4 at participant level was calculated by summing bilateral STS scores (0-2). We used receiver operating characteristic analysis of STS scale for evaluating the diagnostic power of parkinsonism and Spearman's correlation for assessing disease severity. RESULTS: Frequency distribution of STS scale was significantly different in parkinsonism and HC groups, and among PD, PSP, and MSA subgroups. STS scale ≤3 could distinguish parkinsonism from HC with high accuracy (91.78%), PD from HC (91.18%), and MSA from HC (88.71%). STS scale ≤2 could distinguish PSP from HC (96.05%). STS scale = 0 could distinguish PSP from PD (70.24%) and PSP from MSA (72.73%). STS scale was negatively correlated with H-Y stage (P = 0.007, r = -0.359) and duration of disease (P = 0.006, r = -0.367) in PD patients. CONCLUSION: STS scale on SMWI may serve as a useful imaging biomarker for diagnosis of parkinsonism and disease progression evaluation in PD.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32365947

RESUMO

An increasing number of studies have demonstrated that blue space can promote the recovery of the human body, as does green space. However, the influence of blue space on the color space has been studied much less. Based on research on color psychology and healthy cities, the current study takes Yijie District of Dujiangyan City as the research object. Logistic regression models and the semantic differential method was used to explore residents' perceptions of color space and their restorative ratings of blue space. This study describes the characteristics of the people visiting blue space, investigates whether the benefits brought about by blue space are related to the color space, and studies whether the surrounding colors in the blue space have a positive effect in promoting residents' perceptions of pleasure. Based on residents' choices of environmental pictures containing various colors, a color tendency map was constructed. The results revealed strong correlations between residents' perceived pleasure and color space color collocation. Socio-demographic factors were found to affect the frequency of visiting blue space. Reasonable color planning is necessary for human health. Based on the study findings, relevant planning suggestions are proposed as a reference basis for waterfront space color planning.

5.
Nanoscale ; 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32350498

RESUMO

It is highly desirable to improve charge separation and to provide catalytic functions for the efficient photocatalytic CO2 reduction reaction (CO2RR) on g-C3N4 (CN). Here, dimension-matched ultrathin NiMOF/CN heterojunctions have been successfully constructed by the in situ growth of NiMOF nanosheets on hydroxylated and 1,4-aminobenzoic acid (AA) functionalized CN nanosheets, respectively, with ultrasonic assistance. The resultant NiMOF/CN heterojunctions exhibited excellent photocatalytic activities for the CO2RR to produce CO and CH4, especially NiMOF/CN-AA, which had photoactivity 18 times higher than that of bare CN. Based on the surface photovoltage responses, wavelength-dependent photocurrent action spectra, electrochemical impedance spectra, and CO2 electrochemical reduction data, it is clearly confirmed that the exceptional photoactivity mainly resulted from the favorable charge transport properties of ultrathin CN and coupled NiMOF, and from the greatly enhanced charge separation via excited high-level electron transfer from CN to NiMOF in the resultant intimately contacted heterojunction caused by the induction effect of AA, and also from the provided catalytic functionality of the central Ni(ii) for CO2 activation. This work provides a feasible synthetic protocol to fabricate MOF-containing dimension-matched heterojunctions with good charge separation for efficient photocatalysis.

6.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(3): 250-256, 2020 Mar 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-32386015

RESUMO

OBJECTIVES: To determine imaging features of coronavirus disease 2019 (COVID-19) in different stages, and to provide foundations for early diagnosis and treatment. METHODS: CT image data of 187 COVID-19 patients were analyzed in the period of hospitalization. CT scanning was performed on admission and repeated every 3 days. The improvement time of clinical symptoms and the image changes of follow-up CT were statistically analyzed. RESULTS: All 187 patients' nucleic acid test were positive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The early CT images of lung in 187 cases (100%) showed multiple patchy and ground-glass opacities with fine mesh and consolidation shade, which mainly distributed in pulmonary band or under the pleura. In the progressive stage, the pulmonary lesions in 146 cases (78.1%) were mainly consolidation, accompanied by air bronchogram, thickening of blood vessels, and interstitial changes. Severe pulmonary CT images in 15 cases (8%) showed diffuse lesions in both lungs, displaying consolidation, or "white lung". The CT imaging features in 185 cases (98.9%) at the absorptive period showed that the lesions diminished and fibrogenesis. The imaging features of 6 times of lung CT examination in one case showed continuous progress. The original lesion in one case was obviously absorbed, but new lesions appeared under the pleura of both lungs at the third review of CT scanning. The changes of CT imaging lesions during follow-up were significantly different in different clinical symptoms improvement time (P< 0.01). CONCLUSIONS: Images of COVID-19 in various stages have special characteristics. The change of clinical symptoms is synchronous with the change of reexamination CT. Follow-up CT can reflect the trend of clinical changes. Repeat CT examination plays an important role in the early clinical diagnosis and the evaluation for the therapeutic effect on COVID-19 patient.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Humanos , Pandemias , Tomografia Computadorizada por Raios X
7.
J Agric Food Chem ; 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32427469

RESUMO

Insect growth regulators (IGRs) can cause abnormal growth and development in insects, resulting in incomplete metamorphosis or even death of the larvae. Ecdysone receptor and chitinase in insects play indispensable roles in the molting process. Ecdysone analogues and chitinase inhibitors are considered as potential IGRs. In order to find new and highly effective IGRs candidates, based on the structure-activity relationship and molecular docking results of the active compound 6i (3-(tert-butyl)-N-(4-(tert-butyl)phenyl)-1-phenyl-1H-pyrazole-5-carboxamide) discovered in our previous work, we changed the t-butyl group on the pyrazole ring into heptacycle to enhance the hydrophobicity. Consequently, a series of novel heptacyclic pyrazolamide derivatives were designed and synthesized. The bioassay results exhibited that some compounds showed obvious insecticidal activity. Especially, D-27 (N-(4-(tert-butyl)phenyl)-2-phenyl-2,4,5,6,7,8-hexahydrocyclohepta[c]pyrazole-5-carboxamide) had good activities against Plutella xylostella (LC50, 51.50 mg·L-1 ) and Mythimna separata (100% mortality at 2.5 mg·L-1 ). Furthermore, proteins validation indicated that D-27 not only act on the EcR but also inhibit chitinase Of ChtI. Molecular docking and molecular dynamics simulation explained the vital factors in the interaction between D-27 and receptors. D-27 may be a new lead candidate with a dual-target in which Of ChtI shall be the main one. This work created a new starting point for discovering novel type of IGRs.

8.
Cell ; 181(2): 325-345.e28, 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32302571

RESUMO

The mechanisms underlying ribonucleoprotein (RNP) granule assembly, including the basis for establishing and maintaining RNP granules with distinct composition, are unknown. One prominent type of RNP granule is the stress granule (SG), a dynamic and reversible cytoplasmic assembly formed in eukaryotic cells in response to stress. Here, we show that SGs assemble through liquid-liquid phase separation (LLPS) arising from interactions distributed unevenly across a core protein-RNA interaction network. The central node of this network is G3BP1, which functions as a molecular switch that triggers RNA-dependent LLPS in response to a rise in intracellular free RNA concentrations. Moreover, we show that interplay between three distinct intrinsically disordered regions (IDRs) in G3BP1 regulates its intrinsic propensity for LLPS, and this is fine-tuned by phosphorylation within the IDRs. Further regulation of SG assembly arises through positive or negative cooperativity by extrinsic G3BP1-binding factors that strengthen or weaken, respectively, the core SG network.

9.
Biochem Pharmacol ; 177: 113984, 2020 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-32311348

RESUMO

Pluripotent stem cells are have therapeutic applications in regenerative medicine and drug discovery. However, the differentiation of stem cells in vitro hinders their large-scale production and clinical applications. The maintenance of cell pluripotency relies on a complex network of transcription factors; of these, octamer-binding transcription factor-4 (Oct4) plays a key role. This study aimed to construct an Oct4 gene promoter-driven firefly luciferase reporter and screen small-molecule compounds could maintain cell self-renewal and pluripotency. The results showed that ethyl-p-methoxycinnamate (EPMC) enhance the promoter activity of the Oct4 gene, increased the expression of Oct4 at both mRNA and protein levels, and significantly promoted the colony formation of P19 cells. These findings suggesting that EPMC could reinforce the self-renewal capacity of P19 cells. The pluripotency markers Oct4, SRY-related high-mobility-group-box protein-2, and Nanog were expressed at higher levels in EPMC-induced colonies. EPMC could promote teratoma formation and differentiation potential of P19 cells in vivo. It also enhanced self-renewal and pluripotency of human umbilical cord mesenchymal stem cells and mouse embryonic stem cells. Moreover, it significantly activated the nuclear factor kappa B (NF-κB) signaling pathway via the myeloid differentiation factor 88-dependent pathway. The expression level of Oct4 decreased after blocking the NF-κB signaling pathway, suggesting that EPMC promoted the expression of Oct4 partially through the NF-κB signaling pathway. This study indicated that EPMC could maintain self-renewal and pluripotency of stem cells.

10.
Int J Biol Macromol ; 157: 276-287, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32344083

RESUMO

Polysaccharides are important active constituents of Agaricus blazei Morrill. In the present study, WABM-A was isolated from WABM using DEAE-cellulose, and subsequently purified using sepharose CL-6B to obtain the acidic polysaccharide WABM-A-b. WABM-A-b is mainly composed of Glc dextran, with a molecular weight of 10 KDa and ß-1,6-D-Glcp as its main chain. The results of in vivo experiments show that in comparison with the MG, WABM-A significantly reduced the serum levels of TC, TG, and LDL-C, increased the serum levels of HDL-C (P < 0.01), and upregulated the liver expression of PPARγ, LXRα, ABCA1, and ABCG1 in rats with hyperlipidemia (P < 0.05). The results of in vitro experiments show that in comparison with the MG group, WABM-A-b-H significantly reduced the levels of TC and TG in HepG2 cells induced by oleic acid (P < 0.01), and significantly upregulated the protein expression of PPARγ, LXRα, ABCA1, and ABCG1 (P < 0.05). The present study demonstrates that WABM-A-b is an acidic glucan with lipid-lowering activity. The lipid-lowering mechanism of WABM-A-b is via the activation of the PPARγ/LXRα/ABCA1/ABCG1 cholesterol metabolism pathway. This is the first time that the hypolipidemic effect of Agaricus blazei Morrill acidic polysaccharides has been reported.

11.
Curr Eye Res ; : 1-10, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32339463

RESUMO

Purpose: To characterize the aqueous levels of inflammation and ischemia-related biomarkers in a spectrum of retinal ischemic conditions, including neovascular glaucoma (NVG) with stable iris neovascularization after pan retinal photocoagulation (PRP) and anti-VEGF treatment.Methods: Aqueous samples were collected from 139 eyes including NVG (n = 12), stable NVG (n = 26), CRVO (n = 11), NPDR (n = 18), PACG (n = 18), PDR (n = 25), BRVO (n = 7) and cataract (n = 22). The levels of VEGF-A, IL-8 and EPO were measured with ELISA.Results: Aqueous VEGF-A significantly decreased after anti-VEGF and PRP, from 983.79 ± 821.16 pg/ml in the NVG group (n = 11) to 256.50 ± 51.14 pg/ml in the stable NVG group (n = 24) (P = .015). Aqueous VEGF-A in stable NVG group (256.50 ± 51.14 pg/ml, n = 24) was significantly higher (ANOVA, P < .001) than in CRVO (212.10 ± 19.84 pg/ml, n = 7, P = .017), NPDR (221.18 ± 38.21 pg/ml, n = 14, P = .015), BRVO (213.14 ± 48.50 pg/ml, n = 6, P = .028) and cataract group (185.30 ± 34.35 pg/ml, n = 22, P < .001). Aqueous IL-8 in stable NVG group (74.82 ± 10.78 pg/ml, n = 24) was significantly higher (ANOVA, P < .001) than in CRVO (65.19 ± 15.34 pg/ml, n = 11, P = .032) and cataract group (54.11 ± 12.28 pg/ml, n = 22, P < .001). Aqueous EPO in stable NVG group (17.48 ± 3.02 pg/ml, n = 24) was significantly higher (ANOVA, P < .001) than in BRVO (14.98 ± 2.57 pg/ml, n = 7, P = .034) and cataract group (13.50 ± 2.65 pg/ml, n = 22, P < .001). Aqueous concentrations of VEGF-A and IL-8 correlated positively with IOP (r = 0.413, P < .001, r = 0.349, P < .001, respectively, r = correlation coefficient). VEGF-A correlated positively with IL-8 and EPO (P < .001, P = .002, respectively). IL-8 correlated positively with EPO (P < .001).Conclusions: The aqueous levels of VEGF-A, IL-8 and EPO in NVG patients with stable iris neovascularization, who had received PRP and anti-VEGF, were still significantly higher than in control groups with some retinal ischemic conditions.

12.
Biomed Res Int ; 2020: 1473718, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32149077

RESUMO

Background: Portal vein tumor thrombosis (PVTT) is one of the major predictive factors for patients with hepatocellular carcinoma (HCC). The objective of this study was to establish a prognostic nomogram for identifying individual survival outcomes in patients with HCC and PVTT on conservative treatment based on specific factors. Methods: Two hundred and ten patients with HCC and PVTT on conservative treatment in Beijing Ditan Hospital between June 2008 and May 2017 were studied retrospectively as a derivation cohort. We built a nomogram based on independent risk factors for survival prediction. The concordance index (c-index) and a calibration curve were used to evaluate the predictive accuracy. During the study, 102 patients were included at the Putuo Hospital and Third People's Hospital of Changzhou as a validation cohort. Results: In the derivation cohort, the independent factors for overall survival were identified by multivariate analysis, namely, aspartate aminotransferase ≥119 IU/L, gamma-glutamyl transferase ≥115 IU/L, Child-Pugh class C liver function, creatinine ≥91 µmoI/L, α-fetoprotein ≥400 ng/ml, and largest tumor diameter ≥5 cm. The nomogram had a c-index of 0.737 (95% confidence interval, 0.692-0.782) and the calibration curves fitted well. The median survival time was 4.2 months in the derivation cohort, with an MST of 5 months for BCLC C stage and 1.8 months for BCLC D stage patients. Kaplan-Meier analysis showed significant statistical differences in the 6-month overall survival rates of the primary and validation cohorts after the total scores were divided into three quartiles (low risk: 0-85; intermediate risk: 86-210; high risk: ≥211; p < 0.0001 in both cohorts). Conclusions: The nomogram can be a more accurate and individualized prediction for 6-month overall survival of patients with HCC and PVTT on conservative treatment, and it is possible to consider further active interventions for patients in the low-risk group (0-85 scores) to achieve the aim of prolonging survival.

13.
Anal Chim Acta ; 1108: 108-117, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32222232

RESUMO

Ryanodine receptors (RyRs) are calcium release channels located on endoplasmic reticulum (ER) membrane, which play important role in excitation-contraction coupling in muscular response. Flubendiamide represents a novel chemical family of green insecticides which selectively activate invertebrate RyR by interacting with the receptor distinct from the ryanodine binding site and has almost no effect on mammalian ryanodine receptors. Traditional methods to screen RyR modulators involve either radio-labeled RyR substrates or calcium signal-based indirect approaches. However, there is lack of RyR-directed non-isotope molecular tools for RyR agonists/antagonists screening and bioimaging. Here we developed a series of fluorescent probes based on the pharmacophore of flubendiamide with the aims to elucidate the mechanism of diamide insecticides and screen novel RyR-targeting insecticides. These probes revealed the specific RyR staining and in vivo RyR targeting properties in diamondback moth RyR transfected Sf9 cells (Sf9-RyR) and RyR enriched insect tissues. The designed fluorescent probes could induce an effective calcium release from ER membrane of Sf9-RyR cells and also showed competitive RyR binding effect with flubendiamide in cell-based fluorometric assay. Having the non-isotope RyR recognition probes will not only accelerate the screening process of new green agrochemicals but also enables deciphering molecular mechanisms of the high selectivity and the drug resistance associated with the diamides.

14.
Anal Bioanal Chem ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32064570

RESUMO

Here, we developed a microfluidic electrochemical flow cell for fast-scan cyclic voltammetry which is capable of rapid on-chip dilution for efficient and cost-effective electrode calibration. Fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes is a robust electroanalytical technique used to measure subsecond changes in neurotransmitter concentration over time. Traditional methods of electrode calibration for FSCV require several milliliters of a standard. Additionally, generating calibration curves can be time-consuming because separate solutions must be prepared for each concentration. Microfluidic electrochemical flow cells have been developed in the past; however, they often require incorporating the electrode in the device, making it difficult to remove for testing in biological tissues. Likewise, current microfluidic electrochemical flow cells are not capable of rapid on-chip dilution to eliminate the requirement of making multiple solutions. We designed a T-channel device, with microchannel dimensions of 100 µm × 50 µm, that delivered a standard to a 2-mm-diameter open electrode sampling well. A waste channel with the same dimensions was designed perpendicular to the well to flush and remove the standard. The dimensions of the T-microchannels and flow rates were chosen to facilitate complete mixing in the delivery channel prior to reaching the electrode. The degree of mixing was computationally modeled using COMSOL and was quantitatively assessed in the device using both colored dyes and electrochemical detection. On-chip electrode calibration for dopamine with FSCV was not significantly different than the traditional calibration method demonstrating its utility for FSCV calibration. Overall, this device improves the efficiency and ease of electrode calibration. Graphical abstract.

15.
Ann Palliat Med ; 9(2): 483-487, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32075402

RESUMO

Human epidermal growth factor receptor 2 (HER2) mutation and amplification are distinct molecular targets in lung cancer, but the specific targeted therapy for their coexistence is undetermined. Personalized targeted therapy is based on mutation type, with different mutations requiring different treatment. A 64-year-old Chinese woman was diagnosed with advanced lung adenocarcinoma. She was determined as having insertion mutations in exon 20 of the HER2 gene (c.2326G > TTGT) by the amplification refractory mutation system (ARMS) and HER2 gene amplification (HER2/CEP17 ratio 2.6) by fluorescence in situ hybridization (FISH). Thereafter, she was treated with afatinib as first-line therapy, to which she responded. After 2 months, the tumor lesion decreased in size. Computed tomography (CT) follow-up showed stable lung lesions, although she later developed multiple brain metastases and subsequently died of brain failure. Lung adenocarcinoma with coexistent HER2 mutation and amplification is relatively uncommon and has no reported cases on targeted therapy. This case was important because it showed effective response to afatinib and provides evidence to help clinicians identify the therapeutic regimen for such patients.


Assuntos
Adenocarcinoma/genética , Afatinib/uso terapêutico , Neoplasias Pulmonares/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Neoplasias Encefálicas/secundário , Receptores ErbB , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Falha de Tratamento
16.
Pharmacol Res ; 153: 104657, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31982488

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and constitutes a major risk factor for progression to cirrhosis, liver failure and hepatocellular carcinoma (HCC). The occurrence of NAFLD is closely associated with abnormal lipid metabolism and implies a high risk of type 2 diabetes and cardiovascular disease. Therefore, specific and effective drugs for the prevention and treatment of NAFLD are necessary. Hypericin (HP) is one of the main active ingredients of Hypericum perforatum L., and we previously revealed its protective role in islet ß-cells and its effects against type 2 diabetes. In this study, we aimed to explore the preventive and therapeutic effects of HP against NAFLD and the underlying mechanisms in vitro and in vivo. Here, we demonstrated that HP improved cell viability by reducing apoptosis and attenuated lipid accumulation in hepatocytes both in vitro and in vivovia attenuating oxidative stress, inhibiting lipogenesis and enhancing lipid oxidization. Thus, HP exhibited significant preventive and therapeutic effects against HFHS-induced NAFLD and dyslipidemia in mice. Furthermore, we demonstrated that HP directly bound to PKACα and activated PKA/AMPK signaling to elicit its effects against NAFLD, suggesting that PKACα is one of the drug targets of HP. In addition, the enhancing effect of HP on lipolysis in adipocytes through the activation of PKACα was also elucidated. Together, the conclusions indicated that HP, of which one of the targets is PKACα, has the potential to be used as a preventive or therapeutic drug against NAFLD or abnormal lipid metabolism in the future.

17.
Molecules ; 25(1)2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31906574

RESUMO

Background: Dracocephalum peregrinum L., a traditional Kazakh medicine, has good expectorant, anti-cough, and to some degree, anti-asthmatic effects. Diosmetin (3',5,7-trihydroxy-4'-methoxyflavone), a natural flavonoid found in traditional Chinese herbs, is the main flavonoid in D. peregrinum L. and has been used in various medicinal products because of its anticancer, antimicrobial, antioxidant, estrogenic, and anti-inflammatory effects. The present study aimed to investigate the effects of diosmetin on the proliferation, invasion, and migration of glioma cells, as well as the possible underlying mechanisms. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), scratch wound, and Transwell assays were used to demonstrate the effects of diosmetin in glioma. Protein levels of Bcl-2, Bax, cleaved caspase-3, transforming growth factor-ß (TGF-ß), E-cadherin, and phosphorylated and unphosphorylated smad2 and smad3 were determined by Western blots. U251 glioma cell development and progression were measured in vivo in a mouse model. Results: Diosmetin inhibited U251 cell proliferation, migration, and invasion in vitro, the TGF-ß signaling pathway, and Bcl-2 expression. In contrast, there was a significant increase in E-cadherin, Bax, and cleaved caspase-3 expression. Furthermore, it effectively reduced the tumorigenicity of glioma cells and promoted apoptosis in vivo. Conclusion: The results of this study suggest that diosmetin suppresses the growth of glioma cells in vitro and in vivo, possibly by activating E-cadherin expression and inhibiting the TGF-ß signaling pathway.

18.
Neuron ; 105(6): 975-991.e7, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-31926610

RESUMO

Alzheimer's disease (AD) displays a long asymptomatic stage before dementia. We characterize AD stage-associated molecular networks by profiling 14,513 proteins and 34,173 phosphosites in the human brain with mass spectrometry, highlighting 173 protein changes in 17 pathways. The altered proteins are validated in two independent cohorts, showing partial RNA dependency. Comparisons of brain tissue and cerebrospinal fluid proteomes reveal biomarker candidates. Combining with 5xFAD mouse analysis, we determine 15 Aß-correlated proteins (e.g., MDK, NTN1, SMOC1, SLIT2, and HTRA1). 5xFAD shows a proteomic signature similar to symptomatic AD but exhibits activation of autophagy and interferon response and lacks human-specific deleterious events, such as downregulation of neurotrophic factors and synaptic proteins. Multi-omics integration prioritizes AD-related molecules and pathways, including amyloid cascade, inflammation, complement, WNT signaling, TGF-ß and BMP signaling, lipid metabolism, iron homeostasis, and membrane transport. Some Aß-correlated proteins are colocalized with amyloid plaques. Thus, the multilayer omics approach identifies protein networks during AD progression.

19.
Chemosphere ; 244: 125471, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31809932

RESUMO

Biochar is a potential material for making slow-releasing phosphorus (P) fertilizers for the sake of increasing soil P use efficiency and mitigating P losses. However, the long-term effects of P-laden biochars on soil P availability remains unconcerned. In this study, a laboratory-scale 70-days soil incubation experiment was conducted to study the effects of original and P-laden biochars on soil P availability and fractions. Two original biochars were derived from maize stalks by pyrolyzing at 350 °C and 600 °C. P was laden on those biochars by immersing biochars in saturated KH2PO4 solution for 24 h. Eight treatments were set for the incubation experiment, which were soil, soil + triple-superphosphate (TSP), soil + 350 °C biochar, soil + 600 °C biochar, soil + TSP + 350 °C biochar, soil + TSP + 600 °C biochar, soil + 350 °C P-laden biochar, and soil + 600 °C P-laden biochar. Results showed that original biochars could decrease soil available P through P adsorption. And there were no significant differences of soil P fractions under the treatments of mineral P fertilizer and P-laden biochars. Whereas, compared to mineral P fertilizer, P-laden biochars, especially 600 °C P-laden biochar, could maintain soil available P in a significantly higher level across the incubation. It was mainly because of the slow-releasing pattern of P laden on biochar and a more homogeneous soil P source distribution under P-laden biochar treatments. These results indicated that P-laden biochar could work as P fertilizer to improve soil P use efficiency.

20.
Eur Radiol ; 30(3): 1470-1479, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31748853

RESUMO

OBJECTIVES: Antibodies to myelin oligodendrocyte glycoprotein (MOG-ab) and antibodies to aquaporin-4 (AQP4-ab) have been suggested to play roles in commonly separated subsets of patients with neuromyelitis optica spectrum disorder (NMOSD) phenotypes. The aim of this study is to quantitatively delineate and compare the brain lesion distributions of AQP4-ab-positive and MOG-ab-positive patients. METHODS: Fifty-seven and twenty-eight clinical MRI scans were collected from fifty-two AQP4-ab-positive and twenty-four MOG-ab-positive patients, respectively. T2 lesions were segmented manually on each axial FLAIR image. Probabilistic lesion distribution maps were created for each group after spatial normalization. Lobe-wise and voxel-wise quantitative comparisons of the two distributions were performed. A classification model based on the lesion distribution features was constructed to differentiate the two patient groups. RESULTS: Infratentorial and supratentorial brain lesions were found in both AQP4-ab-positive and MOG-ab-positive patients, with large inter-group overlap mainly in deep white matter (WM). In comparison with those in the AQP4 group, the brain lesions of the MOG-ab-positive patients had a larger size, dispersed distribution, and higher probabilities in the cerebellum, pons, midbrain, and GM and juxtacortical WM in temporal, sublobar, frontal, and parietal lobes. The area under the receiver operating characteristic curve of the lesion-distribution-based classification model was 0.951. CONCLUSIONS: MOG-ab-positive and AQP4-ab-positive groups showed similar but quantitatively different brain lesion distributions. These results may help clinicians in considering MOG versus AQP4 in initial diagnosis, and add rationale for sending corresponding serologic testing. KEY POINTS: • Brain lesion distributions of AQP-ab-positive and MOG-ab-positive NMOSD patients • Larger size, dispersed distribution, higher lesion probabilities in the cerebellum, pons, midbrain, and GM and juxtacortical WM in the MOG group • The lesion-distribution-based classification model differentiates the two groups with AUC = 0.951.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA