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1.
Contrast Media Mol Imaging ; 2020: 4764985, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32454803

RESUMO

Background and Aims: Magnetic resonance imaging (MRI) has taken an important role in the diagnosis of inflammatory bowel diseases (IBD). In the wake of current advances in nanotechnology, the drug delivery industry has seen a surge of nanoparticles advertising high specificity in target imaging. Given the rapid development of the field, this review has assembled related articles to explore whether molecular contrast agents can improve the diagnostic capability on gastrointestinal imaging, especially for IBD. Methods: Relevant articles published between 1998 and 2018 from a literature search of PubMed and EMBASE were reviewed. Data extraction was performed on the studies' characteristics, experimental animals, modelling methods, nanoparticles type, magnetic resonance methods, and means of quantitative analysis. Results: A total of 8 studies were identified wherein the subjects were animals, and all studies employed MR equipment. One group utilized a perfluorocarbon solution and the other 7 groups used either magnetic nanoparticles or gadolinium- (Gd-) related nanoparticles for molecular contrast. With ultrasmall superparamagnetic iron oxide (USPIO) particles and Gd-related nanoparticles, signal enhancements were found in the mucosa or with focal lesion of IBD-related model in T1-weighted images (T1WI), whereas superparamagnetic iron oxide (SPIO) particles showed a signal decrease in the intestinal wall of the model in T1WI or T2-weighted images. The signal-to-noise ratio (SNR) was employed to analyze bowel intensity in 3 studies. And the percentage of normalized enhancement was used in 1 study for assessing the severity of inflammation. Conclusion: Molecular MRI with contrast agents can improve the early diagnosis of IBD and quantitate the severity of inflammation in experimental studies.

2.
Phys Chem Chem Phys ; 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32453312

RESUMO

A straightforward strategy is developed to improve the injection efficiency of hot electrons in a Ag/TiO2 plasmonic photocatalyst by introducing Fe as a dopant. The Fe dopant energy level formed within the bandgap of TiO2 provides an extra electron transfer channel for transferring the hot electrons induced by plasmonic Ag nanoparticles.

3.
J Ethnopharmacol ; 257: 112858, 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32278030

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Renal fibrosis (RF) is a common outcome of various progressive chronic kidney diseases (CKDs) and, thus, seriously endangers human health. As the active ingredient of Amygdalus mongolica, amygdalin inhibits RF. Furthermore, our previous studies demonstrated that n-butanol extract (BUT) and petroleum ether extract (PET), which are effective components of A. mongolica, have an anti-renal fibrosis effect. However, their potential mechanisms of action are unclear and need further verification. AIMS OF THE STUDY: The aims of this study were to further investigate the effects and potential mechanisms of A. mongolica extracts in the treatment of RF. MATERIALS AND METHODS: The animals were divided into the control group, RF model group, PET group and BUT group. The RF rat model was established through unilateral ureteral obstruction (UUO). Biochemical indicators, including blood urea nitrogen (BUN), serum creatinine (Scr), and hydroxyproline (HYP, a routine marker of fibrosis), and the antioxidant index (including superoxide dismutase (SOD) and malondialdehyde (MDA)) were measured to evaluate the anti-RF effects of the extracts of A. mongolica. The histomorphology of renal tissue was observed and scored by HE and Masson staining. A serum metabonomic analysis based on UPLC-Q-TOF/MS was performed to assess the changes in the metabolic profile among the different groups. RESULTS: The results showed that PET and BUT significantly improved tubulointerstitial damage and fibrosis by reducing the levels of Scr, BUN, HYP, and MDA and increasing the level of SOD. Moreover, no significant differences in efficacy were observed between the BUT and PET groups. According to the metabolomics analysis, seventy-four potential biomarkers were identified, and eight crucial biomarkers were further selected. These key biomarkers significantly contributed to RF progression by participating in six metabolic pathways, including pathways involved in arginine and proline metabolism, histidine metabolism, nicotinamide metabolism, pentose and glucuronate interconversion, ascorbate and aldarate metabolism, and amino sugar and nucleotide sugar metabolism. In addition, eight key biomarkers and six crucial biomarkers were restored to levels similar to those observed in controls following the treatment with PET and BUT, respectively. CONCLUSIONS: The outcomes of these studies demonstrate the renoprotective effects of A. mongolica extracts in rats with RF and revealed the mechanism underlying these antifibrotic effects on metabolic activity for the first time.

4.
Curr Biol ; 30(10): 1970-1977.e4, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32275878

RESUMO

The plant hormone auxin serves as central regulator of growth and development. Auxin transporters in the plasma membrane are assumed to define tissue-level patterns of auxin distribution [1, 2]. However, auxin is small enough to diffuse through the plasmodesmata that connect neighboring cells [3], presenting an alternative pathway, whose contribution to auxin transport remained largely unexplored [4]. Here, photoactivation microscopy [5, 6] was used to measure the capacity for small-molecule diffusion in the epidermis of Arabidopsis thaliana leaves. In the elongated epidermis cells covering the midrib and petiole, the plasmodesmata-mediated cell-wall permeability was found to be several times higher in the longitudinal than in the transverse direction. The physiological relevance of this asymmetry was tested through quantification of the shade-avoidance response, which depends on auxin transport from the leaf tip to the petiole in the abaxial side of the leaf [7], with the hypothesis that directionality of diffusion supplements transporter-mediated auxin movement [8]. Triggering the response by auxin application at the tip led to stronger leaf movement in wild-type plants than in gsl8 mutants [9], which lack the callose synthase necessary to establish directionality. The results match the predictions of a mathematical model of auxin transport based on the permeabilities measured in wild-type and mutant plants. It is concluded that plasmodesmata permeability can be selectively modulated within a plant cell and that the conferred directionality in diffusion can influence the tissue-specific distribution patterns of small molecules, like auxin. VIDEO ABSTRACT.

5.
J Environ Manage ; 263: 110407, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32174538

RESUMO

Land use change affected by wide ranges of human activities is a key driver of global climate change. In the last three decades, China has experienced unprecedented land use change accompanied by increasing environmental problems. There is a pressing need to project and analyze long-term land use scenarios that are critical for land use planning and policymaking. Using GlobeLand30 data, we examined China's land use change from 2000 to 2010, and developed a novel LandCA model for scenario projections from 2020 to 2050. The observed and projected land use change (2000-2050) was analyzed in terms of the interval, category, and transition levels. Our findings show that land Exchange intensity is more than 3 times greater than land Quantity intensity from 2000 to 2050, and the overall rate of land use change will decelerate from 2010 to 2050. During 2000-2010, the loss of built-up land to other categories was 12.7% while the gain was 32.5%, with a growth rate 3.4 times larger than that during 2010-2050. The total amount of cultivated land continuously decreases but will not violate the Chinese "Cultivated Land Red-Line Restriction" by 2050. We speculate that the government's goal of 26% forest cover by 2050 may not be achieved, as a result of strict land use policies preventing the transformation from cultivated land to forests. This study contributes to new evaluations of long-term land use change in China for the government to adjust policies and regulations for sustainable development.

6.
New Phytol ; 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32222083

RESUMO

MicroRNAs play important roles in the regulation of gene expression in plants and animals. However, little information is known about the action mechanism and function of fungal microRNA-like RNAs (milRNAs). In this study, combining deep sequencing, molecular and histological assays, milRNAs and their targets in the phytopathogenic fungus Valsa mali were isolated and identified. A critical milRNA, Vm-milR16, was identified to adaptively regulate the expression of virulence genes. Fourteen isolated milRNAs showed high expression abundance. Based on the assessment of a pathogenicity function of these milRNAs, Vm-milR16 was found to be a critical milRNA in V. mali by regulating sucrose non-fermenting 1 (VmSNF1), 4,5-DOPA dioxygenase extradiol (VmDODA), and a hypothetical protein (VmHy1). During V. mali infection, Vm-milR16 is downregulated, while its targets are upregulated. Overexpression of Vm-milR16, but not mutated Vm-milR16, significantly reduces the expression of targets and virulence of V. mali. Furthermore, deletion of VmSNF1, VmDODA and VmHy1 significantly reduce virulence of V. mali. All three targets seem to be essential for oxidative stress response and VmSNF1 is required for expression of pectinase genes during V. mali-host interaction. Our results demonstrate Vm-milRNAs contributing to the infection of V. mali on apple trees by adaptively regulating virulence genes.

7.
Proc Natl Acad Sci U S A ; 117(11): 6223-6230, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32123097

RESUMO

All multicellular organisms keep a balance between sink and source activities by controlling nutrient transport at strategic positions. In most plants, photosynthetically produced sucrose is the predominant carbon and energy source, whose transport from leaves to carbon sink organs depends on sucrose transporters. In the model plant Arabidopsis thaliana, transport of sucrose into the phloem vascular tissue by SUCROSE TRANSPORTER 2 (SUC2) sets the rate of carbon export from source leaves, just like the SUC2 homologs of most crop plants. Despite their importance, little is known about the proteins that regulate these sucrose transporters. Here, identification and characterization of SUC2-interaction partners revealed that SUC2 activity is regulated via its protein turnover rate and phosphorylation state. UBIQUITIN-CONJUGATING ENZYME 34 (UBC34) was found to trigger turnover of SUC2 in a light-dependent manner. The E2 enzyme UBC34 could ubiquitinate SUC2 in vitro, a function generally associated with E3 ubiquitin ligases. ubc34 mutants showed increased phloem loading, as well as increased biomass and yield. In contrast, mutants of another SUC2-interaction partner, WALL-ASSOCIATED KINASE LIKE 8 (WAKL8), showed decreased phloem loading and growth. An in vivo assay based on a fluorescent sucrose analog confirmed that SUC2 phosphorylation by WAKL8 can increase transport activity. Both proteins are required for the up-regulation of phloem loading in response to increased light intensity. The molecular mechanism of SUC2 regulation elucidated here provides promising targets for the biotechnological enhancement of source strength.

9.
BMC Cancer ; 20(1): 100, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32024483

RESUMO

BACKGROUND: The purpose of this study was to investigate the value of wavelet-transformed radiomic MRI in predicting the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) for patients with locally advanced breast cancer (LABC). METHODS: Fifty-five female patients with LABC who underwent contrast-enhanced MRI (CE-MRI) examination prior to NAC were collected for the retrospective study. According to the pathological assessment after NAC, patient responses to NAC were categorized into pCR and non-pCR. Three groups of radiomic textures were calculated in the segmented lesions, including (1) volumetric textures, (2) peripheral textures, and (3) wavelet-transformed textures. Six models for the prediction of pCR were Model I: group (1), Model II: group (1) + (2), Model III: group (3), Model IV: group (1) + (3), Model V: group (2) + (3), and Model VI: group (1) + (2) + (3). The performance of predicting models was compared using the area under the receiver operating characteristic (ROC) curves (AUC). RESULTS: The AUCs of the six models for the prediction of pCR were 0.816 ± 0.033 (Model I), 0.823 ± 0.020 (Model II), 0.888 ± 0.025 (Model III), 0.876 ± 0.015 (Model IV), 0.885 ± 0.030 (Model V), and 0.874 ± 0.019 (Model VI). The performance of four models with wavelet-transformed textures (Models III, IV, V, and VI) was significantly better than those without wavelet-transformed textures (Model I and II). In addition, the inclusion of volumetric textures or peripheral textures or both did not result in any improvements in performance. CONCLUSIONS: Wavelet-transformed textures outperformed volumetric and/or peripheral textures in the radiomic MRI prediction of pCR to NAC for patients with LABC, which can potentially serve as a surrogate biomarker for the prediction of the response of LABC to NAC.

10.
Sci Total Environ ; 712: 136509, 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-31931202

RESUMO

Driven by increasing urban demand, spatially-varying urban expansion has led to significant ecosystem degradation in China and elsewhere. Spatial nonstationarity affects the relationship between urban expansion and ecosystem service value (ESV) loss, but its significance has been under-emphasized. To study the spatially-heterogeneous ESV loss, we integrated cellular automata (CA) with geographically weighted regression (GWR) in a model that considers the relationships between urban expansion and its driving factors. We used ten GWR bandwidths to construct the CAGWR models for reproducing rapid urban expansion at Chongqing from 2005 to 2010. We then used the CAGWR model with the best bandwidth to predict future urban scenarios out to 2030. Our modeling shows that CAGWR is strongly sensitive to bandwidth, and that the overall accuracy and Figure-of-Merit are maximized with a ~2 km2 bandwidth (about 150 samples). We examined ESV losses in eleven ecosystem classes and found that climate regulation and water flow regulation are the dominant drivers of ESV loss. From 2010 to 2030, Chongqing's urban area will increase by about 87%, resulting in substantial encroachment on agricultural land, dryland and shrubs, causing significant ESV losses of about 38%. Our results constitute an early warning of ecosystem degradation caused by massive urban development. This study improves our understanding of spatially-varying urban expansion and related ESV losses in rapidly developing areas and should help improve urban planning regulation and regional policy for sustainable development to maintain environmentally-friendly cities.

11.
Physiol Rev ; 100(2): 673-694, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31751167

RESUMO

The central dogma of molecular biology illustrates the importance of mRNAs as critical mediators between genetic information encoded at the DNA level and proteomes/metabolomes that determine the diverse functional outcome at the cellular and organ levels. Although the total number of protein-producing (coding) genes in the mammalian genome is ~20,000, it is evident that the intricate processes of cardiac development and the highly regulated physiological regulation in the normal heart, as well as the complex manifestation of pathological remodeling in a diseased heart, would require a much higher degree of complexity at the transcriptome level and beyond. Indeed, in addition to an extensive regulatory scheme implemented at the level of transcription, the complexity of transcript processing following transcription is dramatically increased. RNA processing includes post-transcriptional modification, alternative splicing, editing and transportation, ribosomal loading, and degradation. While transcriptional control of cardiac genes has been a major focus of investigation in recent decades, a great deal of progress has recently been made in our understanding of how post-transcriptional regulation of mRNA contributes to transcriptome complexity. In this review, we highlight some of the key molecular processes and major players in RNA maturation and post-transcriptional regulation. In addition, we provide an update to the recent progress made in the discovery of RNA processing regulators implicated in cardiac development and disease. While post-transcriptional modulation is a complex and challenging problem to study, recent technological advancements are paving the way for a new era of exciting discoveries and potential clinical translation in the context of cardiac biology and heart disease.

12.
Neurosci Lett ; 721: 134631, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-31734291

RESUMO

BACKGROUND: Remifentanil induces hyperalgesia, but the underlying mechanisms are not fully understood. Acid-sensing ion channel 3 (ASIC3) plays a regulatory role in the pain pathway. This study aimed to explore the effect of remifentanil administration on postoperative pain and on ASIC3 expression at the prespinal and supraspinal levels in a rat model. METHODS: Rats were randomly allocated to the control, incision, remifentanil, and remifentanil + incision groups. Remifentanil was given by a 1-h intravenous infusion prior to plantar incision. Paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured at different time points before and after incision to evaluate mechanical and thermal hyperalgesia, respectively. The dorsal root ganglion (DRG), hippocampus, and hypothalamus were obtained after sacrifice at 48 h post-incision for determination of the protein expression of ASIC3 using western blot. RESULTS: Remifentanil administration significantly induced mechanical and thermal hyperalgesia from 2 to 48 h after incision. In addition, remifentanil exposure remarkably stimulated ASIC3 protein expression in DRG, hippocampus, and hypothalamus of rats at 48 h after incision. CONCLUSION: Remifentanil-induced hyperalgesia is accompanied by increased ASIC3 expression at the DRG and supraspinal levels, implying a possible involvement of ASIC3 in remifentanil-induced hyperalgesia.

13.
Inorg Chem ; 59(1): 717-729, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31829583

RESUMO

Single-ion magnets based on lanthanide ions in pseudo-D5h symmetry have gained much attention in recent years as they are reported to possess a large blocking temperature and a large barrier for magnetization reversal. Magneto-structural correlations reveal that the axial O-Ln-O angle is an important parameter to control the barrier, and while it can be fine-tuned by chemical modification, an alternative would be to utilize hydrostatic pressure. Herein, we report the crystal structures and static magnetic properties of two air-stable isostructural lanthanide SIMs under applied pressures. The complexes exhibit pseudo-D5h symmetry around the Ln(III)-ion (Ln = Dy or Ho), which coordinates to five equatorial water molecules and two large neutral phosphonic diamide ligands along the axial direction. High-pressure single-crystal X-ray diffraction experiments revealed two phase-transitions and an increasing deviation from D5h-symmetry between ambient pressure and 3.6 GPa. High-pressure direct-current magnetic measurements of the Dy(III) compound showed large steps in the hysteresis loops near zero field, indicative of quantum tunneling of magnetization (QTM). These steps grow in size with increasing pressure, suggesting that QTM becomes progressively more active, which correlates well with the pressure-induced increased overall deviation from pseudo-D5h symmetry and decreasing axial O-Dy-O angle. A strong temperature dependence of the step size is seen at 0.3 GPa, which shows that the SMM character persists even at this pressure. To understand the origin of significant variation in the tunneling probability upon pressure, we performed a range of ab initio calculations based on the CASSCF/RASSI-SO/SINGLE_ANISO method on both Dy and Ho complexes. From the energies and magnetic anisotropy of the mJ sublevels, we find a complex variation of the energy barrier with pressure, and using a constructed geometrical parameter, R, taking into account changes in both bond angles and distances, we link the magnetic properties to the first coordination sphere of the molecules.

14.
Biomacromolecules ; 21(2): 613-620, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31841316

RESUMO

Herein we report the synthesis of a cellulose-grafted bottlebrush copolymer with nucleobases as hydrophobic moieties. Well-defined spherical micelles from this bottlebrush copolymer were fabricated via a solvent switch method. A morphological transition from spheres to worms was only observed to occur when a diblock copolymer with a complementary nucleobase functionality was introduced. Hydrophobic interaction is not capable of triggering the morphological transformation, and the diblock copolymer with the heterogeneous acrylamide nucleobase monomer can induce the morphological transition at higher A:T molar ratios, which might be caused by the weak H-bonding interaction. This supramolecular "grafting to" method enables the preparation of a series of nanoparticles with similar shapes and dimensions but distinct surface properties such as zeta potentials. Moreover, reversible morphological transitions between worm-like micelles and spheres can be achieved using a reversible collapsing and swelling of a thermoresponsive polymer. This work highlights that a supramolecular "grafting to" approach between complementary nucleobases can be utilized to tune morphologies and surface properties of nanoparticles.

15.
Nat Chem ; 12(2): 213-219, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31844195

RESUMO

The distribution of electrons in the 4f orbitals of lanthanide ions is often assigned a crucial role in the design of single-molecule magnets, which maintain magnetization in zero external field. Optimal spatial complementarity between the 4f-electron density and the ligand field is key to maximizing magnetic anisotropy, which is an important factor in the ability of lanthanide complexes to display single-molecule magnet behaviour. Here we have experimentally determined the electron density distribution in two dysprosium molecular complexes by interpreting high-resolution synchrotron X-ray diffraction with a multipole model. The ground-state 4f-electron density is found to be an oblate ellipsoid, as is often deduced from a simplified Sievers model that assumes a pure |±15/2> ground-state doublet for the lanthanide ion. The large equatorial asymmetry-determined by a model wavefunction-was found to contain considerable MJ mixing of |±11/2> and only 81% of |±15/2>. The experimental molecular magnetic easy axes were recovered, and found to deviate by 13.1° and 8.7° from those obtained by ab initio calculations.

16.
Animals (Basel) ; 9(12)2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31795068

RESUMO

The aims of this study were to assess the effects of increasing levels of DFRB as a replacement for corns on intestinal physical barrier function and bacteria of finishing pigs. A total of 35 castrated finishing pigs (age: 158.5 ± 2.0 d, initial body weight: 62.9 ± 0.8 kg) were randomly divided into five dietary treatments (seven replicates/treatment) for a 28-day experimental period, i.e., a control diet with basal diet, and four experimental diets in which maize was replaced by 7%, 14%, 21%, and 28% DFRB, respectively. The results showed that serum endotoxins concentration and diamine oxidase (DAO) activity were both increased (linear, p = 0.0004, 0.001, respectively) with DFRB level. However, compared with control group, serum endotoxins concentration and DAO activity were not different in pigs fed with 7% DFRB in the diet. There was a quadratic response in serum D-lactate concentration to the increased DFRB (quadratic, p = 0.021). In the cecum, thickness of the intestinal wall significantly increased with increasing levels of DFRB in the diets (linear, p = 0.033), while crypt depth/thickness of the intestinal wall ratio significantly decreased with increasing level of DFRB in the diets (linear, p = 0.043). In the jejunum, total bacteria, Escherichia coli, and Bifidobacterium all responded quadratically to increasing levels of DFRB in the diets (quadratic, p = 0.003, 0.001, 0.006, respectively). Additionally, there was no difference in Escherichia coli in pigs fed 0%, 7%, and 14% DFRB diets. In the colon, there were quadratic responses in C. perfringens to the increased DFRB (quadratic, p = 0.023). C. perfringens reduced as the DFRB concentration increased from 0% to 14% and then increased. When D-lactate, total bacteria, Escherichia coli, Bifidobacterium, and C. perfringens were considered, the optimal substitution level of DFRB were 12.00%, 11.84%, 7.50%, 8.92%, and 15.92%, respectively. In conclusion, 7% DFRB had a beneficial effect on intestinal wall thickness, Bifidobacterium and C. perfringens, and had no adverse effect on intestinal permeability and Escherichia coli.

17.
Anim Biotechnol ; : 1-9, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31809636

RESUMO

Carnitine palmitoyltransferase 1a (CPT1a) is a rate-limited enzyme in the mitochondrial fatty acid ß-oxidation pathway. It acts as a bridge between PPARα and the fatty acid oxidation pathways and is closely related to ruminant growth and development. In this study, one 12 bp InDel polymorphism of the CPT1a gene was identified in 700 goats, and we designated these three genotypes II, ID, and DD. Association analysis showed that the InDel polymorphism was closely associated with trunk index (p = 0.008) and body length index (p = 0.034) in Hainan black goats, and body length (p = 0.010), chest circumference (p = 0.004), chest depth (p = 0.029), and huckle bone width (p = 0.002) in Nubian goats, as well as the chest circumference (p = 0.016) in the Fuqing goat breed. In both kids and adult goats, qRT-PCR results showed that the CPT1a gene was expressed in all tissues, showing the highest mRNA levels in the liver, lung, spleen, and kidney, followed by the adipose tissue and brain. This indicates an association between the InDel of the CPT1a gene and growth traits in selected goat breeds, which may facilitate marker-assisted selection in goat genetics and breeding.

18.
Prion ; 13(1): 173-184, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-31814527

RESUMO

Aquaporins (AQPs) are widely expressed in various types of tissues, among them AQP1, AQP4 and AQP9 are expressed predominately with relatively special distributing features in various brain regions. The aberrant changes of AQP1 and AQP4 have been observed in the brains of Alzheimer disease (AD). To evaluate the underlying alteration of brain AQPs in prion diseases, scrapie strains of 139A, ME7 and S15 infected mice were tested in this study. Western blots revealed markedly increased levels of AQP1, AQP4 and AQP9 in the brain tissues of all tested scrapie-infected mice collected at terminal stage. Analyses of the AQPs levels in the brain tissues collected at different time-points during incubation period showed time-dependent increased in 139A and ME7-infected mice, especially at the middle-late stage. The AQP1 levels also increased in the cortex regions of some human prion diseases, including the patients with sporadic Creutzfeldt-Jakob disease (CJD), fatal familial insomnia (FFI) and G114V genetic CJD (gCJD). Immunohistochemistry (IHC) assays verified that the AQPs-positive cells were astrocyte-like morphologically; meanwhile, numerous various sizes of AQPs-positive particles and dots were also observable in the brain sections of scrapie-infected mice. Immunofluorescent assays (IFAs) illustrated that the signals of AQPs colocalized with those of the GFAP positive proliferative astrocytes, and more interestingly, appeared to overlap also with the signals of PrP in the brains of scrapie-infected mice. Moreover, IHC assays with a commercial doublestain system revealed that distributing areas of AQPs overlapped not only with that of the activated large astrocytes, but also with that of abundantly deposited PrPSc in the brain tissues of scrapie murine models. Our data here propose the solid evidences that the expressions of brain AQP1, AQP4 and AQP9 are all aberrantly enhanced in various murine models of scrapie infection. The closely anatomical association between the accumulated AQPs and deposited PrPSc in the brain tissues indicates that the abnormally increased water channel proteins participate in the pathogenesis of prion diseases.

19.
Invest New Drugs ; 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31823159

RESUMO

The PI3K pathway is aberrantly activated in many cancers and plays a critical role in tumour cell proliferation and survival, making it a rational therapeutic target. In the present study, the effects and the underlying mechanism of a new PI3K inhibitor, W941, were investigated in non-small-cell lung cancer (NSCLC). The results of this study showed that W941 inhibited the growth of A549 and Hcc827 cells with IC50 values of 0.12 and 0.23 µM, respectively, and that W941 markedly inhibited the growth of A549 xenograft tumours in a nude mouse model without decreasing body weight. Western blotting assays showed that W941 inhibited the phosphorylation of downstream proteins in the PI3K pathway (AKT, mTOR, p70S6K and 4EBP1) in both A549 and Hcc827 cells. In addition, after W941 treatment, a dose-dependent increase in the ratio of the LC3-II/I ratio was observed. When cells were pre-treated with chloroquine or bafilomycin A1, W941 increased the LC3-II/I ratio, suggesting that W941 acted as an autophagy inducer. Moreover, autophagy blockers enhanced apoptosis after W941 treatment, indicating that W941-induced autophagy actually protected the cells against its cytotoxicity. Our findings suggest that the combination of a PI3K inhibitor with an autophagy inhibitor might be a novel option for NSCLC treatment.

20.
Animals (Basel) ; 9(11)2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31652864

RESUMO

The present study aimed to identify the molecular markers for genes that influence intramuscular fat content (IFC), but not average backfat thickness (ABT). A total of 330 Suhuai pigs were slaughtered, and measurements of IFC and ABT were obtained. Phenotypic and genetic correlations between IFC and ABT were calculated. Thirteen single nucleotide polymorphisms (SNPs) among 12 candidate genes for IFC were analyzed, including FABP3, LIPE, IGF1, IGF2, LEP, LEPR, MC4R, PHKG1, RETN, RYR1, SCD, and UBE3C. Associations of the evaluated SNPs with IFCIFC and ABT were performed. Our results showed that the means of IFC and ABT were 1.99 ± 0.03 % and 26.68 ± 0.28 mm, respectively. The coefficients of variation (CVs) of IFC and ABT were 31.21% and 19.36%, respectively. The phenotypic and genetic correlations between IFC and ABT were moderate. Only the FABP3 (rs1110770079) was associated with IFC (p < 0.05) but not with ABT. Besides, there was a tendency for associations of RYR1 (rs344435545) and SCD (rs80912566) with IFC (p < 0.1). Our results indicated that the FABP3 (rs1110770079) SNP could be used as a marker to improve IFC without changing ABT in the Suhuai pig breeding system.

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