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1.
IEEE Trans Vis Comput Graph ; 26(1): 906-916, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31478860

RESUMO

Combining data content with visual embellishments, infographics can effectively deliver messages in an engaging and memorable manner. Various authoring tools have been proposed to facilitate the creation of infographics. However, creating a professional infographic with these authoring tools is still not an easy task, requiring much time and design expertise. Therefore, these tools are generally not attractive to casual users, who are either unwilling to take time to learn the tools or lacking in proper design expertise to create a professional infographic. In this paper, we explore an alternative approach: to automatically generate infographics from natural language statements. We first conducted a preliminary study to explore the design space of infographics. Based on the preliminary study, we built a proof-of-concept system that automatically converts statements about simple proportion-related statistics to a set of infographics with pre-designed styles. Finally, we demonstrated the usability and usefulness of the system through sample results, exhibits, and expert reviews.

2.
Ann Palliat Med ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31735045

RESUMO

BACKGROUND: The malnutrition-inflammation score (MIS) is a nutritional scoring system that has been validated in chronic kidney disease (CKD) stages III-V, especially in dialysis patients. We aimed to test whether the MIS changed in the early stages of CKD and whether it was associated with anthropometry and body composition measurements (BCMs) in patients with CKD. METHODS: This was a cross-sectional study conducted in the Nephrology Department. A total of 144 patients with CKD were included in the study between May 2017 and December 2017. The MIS was calculated without computing the dialysis vintage in the scoring. Body composition was measured using a portable whole-body bioimpedance spectroscopy device. Anthropometric, laboratory, and other body composition parameters were recorded. RESULTS: The MIS was increased in patients with CKD. It was negatively correlated with body mass index (BMI), mid-arm muscle circumference (MAMC), handgrip strength, lean tissue index (LTI), fat tissue index (FTI), phase angle (PA), and hemoglobin and albumin concentrations, and it was positively correlated with sex, overhydration, urinary protein excretion and IL-6. A high MIS was significantly correlated with a low LTI (r=-0.274; P=0.001), low FTI (r=-0.179; P=0.032), overhydration (r=0.457; P<0.001) and low PA (r=-0.475; P<0.001). A rather strong correlation was observed between the PA and the MIS. In the multivariate regressions, after adjusting for age, sex, presence of diabetes, handgrip strength, BMI, overhydration, glomerular filtration rate, albumin and IL-6 concentrations, these relationships did not diminish. CONCLUSIONS: The MIS was strongly linked with indicators of nutrition. As a simple and practical tool for assessing nutritional status, the MIS should be calculated in the early stages of CKD.

3.
Drug Deliv ; 26(1): 1125-1139, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31736389

RESUMO

Stability in systemic circulation, effective tumor accumulation, and the subsequent crucial subcellular targeting are significant elements that maximize the therapeutic efficacy of a drug. Accordingly, novel nanoparticles based on polysaccharides that simultaneously presented prolonged systemic circulation and mitochondrial-targeted drug release were synthesized. First, the mitochondrial-targeted polymer, 3,4-dihydroxyphenyl propionic acid-chitosan oligosaccharide-dithiodipropionic acid-berberine (DHPA-CDB), was synthesized, which was used to form self-assembled curcumin (Cur)-encapsulated cationic micelles (DHPA-CDB/Cur). Negatively charged oligomeric hyaluronic acid-3-carboxyphenylboronic acid (oHA-PBA), a ligand to sialic acid and CD44, was further added to the surface of the preformed DHPA-CDB/Cur core to shield the positive charges and to prolong blood persistence. oHA-PBA@DHPA-CDB/Cur formed a covalent polyplex of oHA-PBA and DHPA-CDB/Cur via the pH-responsive borate ester bond between PBA and DHPA. The mildly acidic tumor environment led to the degradation of borate ester bonds, thereby realizing the exposure of the cationic micelles and causing a charge reversal from -19.47 to +12.01 mV, to promote cell internalization and mitochondrial localization. Compared with micelles without the oHA-PBA modification, the prepared oHA-PBA@DHPA-CDB/Cur showed enhanced cytotoxicity to PANC-1 cells and greater cellular uptake via receptor-mediated endocytosis. oHA-PBA@DHPA-CDB/Cur was effectively targeted to the mitochondria, which triggered mitochondrial membrane depolarization. In mice xenografted with PANC-1 cells, compared with control mice, oHA-PBA@DHPA-CDB/Cur resulted in more effective tumor suppression and greater biosafety with preferential accumulation in the tumor tissue. Thus, the long-circulating oHA-PBA@DHPA-CDB/Cur, with mitochondrial targeting and tumor environment charge-reversal capabilities, was shown to be an excellent candidate for subcellular-specific drug delivery.

4.
J Food Biochem ; : e13055, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31591749

RESUMO

The aim of this study was to evaluate the hypoglycemic effects of Pea oligopeptide on the glycemic and lipidemic status of mice with type 2 diabetes (T2D) induced by a high-fat diet and streptozotocin (STZ). Using HPLC-MS/MS spectra processing, 70 significant peptide (2-3 amino acids) sequences were identified, noting four peptides from Pea oligopeptide with a proline residue at the C-terminus, which might have dipeptidase-IV (DPP-IV) inhibitory activity for the treatment of T2D. After a 4-week administration of Pea oligopeptide and metformin, various blood biochemical indexes and organic histopathologies were detected to aid the discussion regarding potential mechanisms. The results showed a significant reduction in the levels of blood glucose, lipid profiles, and liver fat deposition in diabetic mice. Furthermore, Pea oligopeptide and metformin improved glucose tolerance, promoted glycogen synthesis, and protected the liver and kidney structures in diabetic mice. The results indicated that Pea oligopeptide played an essential role in the hypoglycemic effect in the T2D mice model. Practical applications This paper examined the preliminary hypoglycemic activities of Pea oligopeptide in a high-fat diet and STZ-induced T2D mice. Furthermore, four kinds of dipeptides and tripeptides that might exhibit antidiabetic functions were detected using HPLC-MS/MS. The results provided practical knowledge regarding the hypoglycemic effects of Pea oligopeptide and established the foundation of its structure-function relationships.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31623945

RESUMO

INTRODUCTION AND OBJECTIVES: The production and consumption of oysters is increasing annually because it can provide essential nutrients and benefit for human health, leading to frequent occurrence of severe allergic reactions observed in sensitized individuals. The aim of the present study was to investigate the effects of acid and protease treatment on the conformation and IgE-binding capacity of recombinant Crassostrea gigas tropomyosin (Cra g 1). RESULTS: Under acidic conditions, Cra g 1 did not undergo degradation, however, the changes obvious in the intensity of CD signal and ANS-binding fluorescence were observed, which was associated with a decrease in antibody reactivity. In simulated gastrointestinal fluid (SGF) and simulated intestinal fluid (SIF) digestion system, acid-treated Cra g 1 was relatively resistant to digestion, but the degradative patterns were very different. Moreover, owing to alterations of secondary structure and hydrophobic surface of the protein during digestive processing, antigenicity of acid-induced Cra g 1 reduced in SGF while it increased significantly in SIF. CONCLUSION: To our knowledge, this is the first study reporting that antigenicity of acid-treated oyster tropomyosin increased after SIF digestion. These results revealed that treatment with acid and pepsin, rather than trypsin, was an effective way of reducing IgE-binding capacity of tropomyosin from oyster.

6.
Genes Genomics ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31612375

RESUMO

INTRODUCTION: AMP-activated protein kinases (AMPK) are heterotrimeric complexes. The main upstream phosphorylase has AMP-dependent LKB1 and Ca2+-dependent CaMKK beta. AMPK also includes an auto-inhibitory domain and a region associated with beta and gamma subunits, which regulate a variety of cellular activities and energy metabolism. The increase in the ratio of AMP/ATP can stimulate the activation of AMPK. Once AMPK is activated, pathways to ATP consumption (e.g., fat, cholesterol, and protein synthesis) will be shut down. The pathway to ATP generation (e.g., oxidation of fat and glycolysis pathway) will be activated. AMPK genes have not been systematically characterized in marine invertebrates. METHODS: In this study, we identified and characterized three AMPK genes, AMPK-α, AMPK-ß, and AMPK-γ, in the Manila clam (Ruditapes philippinarum). To gain insight into the role of AMPK genes during clam energy metabolism, quantitative real-time PCR was used to investigate the expression profiles in the different stages of clam development, in healthy adult tissues, and after air exposure at two different temperatures. RESULTS: Phylogenetic and protein structural analyses were conducted to determine the identity and evolutionary relationships of these genes. The structural features of the genes were relatively well-conserved, relative to the AMPK genes of other vertebrates. The expression of genes was significantly induced 3-48 h after air exposure. CONCLUSINON: AMPK-α, AMPK-ß and AMPK-γ are involved in clam energy metabolism. Increased expression levels of AMPK genes in the gill and intestine of Manila clam in response to air exposure implied a strong adaptability to the coastal environment.

7.
Chem Commun (Camb) ; 55(94): 14099-14102, 2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31641718

RESUMO

A bean-shaped and dual-functionalized organic-inorganic hybrid supramolecular system with a GSH-dependent turn-on fluorescence enhancement property and stimuli-responsive drug delivery function endowed with leaning towerarene-based switches has been constructed for simultaneous tumor inhibition and imaging.

8.
Bioconjug Chem ; 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31661952

RESUMO

It is very popular to fuse a protein drug or drug candidate to the Fc domain of immunoglobulin G (IgG) in order to prolong the in vivo half-life. In this study, we have designed, prepared, and tested an Fc-fused thermostable cocaine esterase (CocE) mutant (known as E196-301, with the T172R/G173Q/L196C/I301C substitutions on CocE) expressed in E. coli. As expected, Fc-fusion does not affect the in vitro enzyme activity and thermal stability of the enzyme and that Fc-E196-301 can favorably bind FcRn with Kd = 386 ± 35 nM. However, Fc-fusion does not prolong the in vivo half-life of E196-301 at all; Fc-E196-301 and E196-301 have essentially the same PK profile (t1/2 = 0.4 ± 0.1 h) in rats. This is the first time demonstrating that Fc-fusion does not prolong in vivo half-life of a protein. This finding is consistent with the mechanistic understanding that E196-301 and Fc-E196-301 are all degraded primarily through rapid proteolysis in the body. The Fc fusion cannot protect E196-301 from the proteolysis in the body. Nevertheless, it has been demonstrated that PEGylation can effectively protect E196-301, as the PEGylated E196-301, i.e., PEG-E196-301, has a significantly prolonged in vivo half-life. It has also been demonstrated that both E196-301 and PEG-E196-301 have dose-dependent in vivo half-lives (e.g., 19.9 ± 6.4 h for the elimination t1/2 of 30 mg/kg PEG-E196-301), as the endogenous proteolytic enzymes responsible for proteolysis of E196-301 (PEGylated or not) are nearly saturated by the high plasma concentration produced by a high dose of E196-301 or PEG-E196-301.

9.
Integr Zool ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31631517

RESUMO

Twenty Far East Greylag Geese Anser anser rubrirostris were captured and fitted with GPS/GSM loggers to identify breeding and wintering areas, migration routes and stopover sites. Telemetry data for the first time showed linkages between their Yangtze River wintering areas, stopover sites in northeastern China and breeding/molting grounds in eastern Mongolia and northeast China. Ten of the twenty tagged individuals that provided sufficient data stopped on migration at the Yellow River Estuary, Beidagang Reservoir and Xar Moron River confirming these areas as being important stopover sites for this population. The median spring migration duration was 33.7 days (individuals started between 25 February and 16 March and completed 1-9 April) compared to 52.7 days in autumn (26 September-13 October until 4 November-11 December). Median stopover duration was 31.1 and 51.3 days and median speed of travel was 62.6 and 47.9 km/day for spring and autumn migration, respectively. The significant differences between spring and autumn migration on the migration duration, stopover duration and the migration speed confirmed that tagged adult Greylag Geese travelled faster in spring than autumn, supporting the hypothesis that they should be more time-limited during spring migration. This article is protected by copyright. All rights reserved.

10.
Dev Cell ; 50(6): 683-689.e6, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31550462

RESUMO

CENP-A is a centromere-specific histone H3 variant that epigenetically determines centromere identity, but how CENP-A is deposited at the centromere remains obscure. We previously reported that CENP-A K124 ubiquitylation, mediated by the CUL4A-RBX1-COPS8 complex, is essential for CENP-A deposition at the centromere. However, a recent report stated that CENP-A K124R mutants show no defects in centromere localization and cell viability. In the present study, we found that EYFP tagging induces additional ubiquitylation of EYFP-CENP-A K124R, which allows the mutant protein to bind to HJURP. Using a previously developed conditional CENP-A knockout system and our CENP-A K124R knockin mutant created by the CRISPR-Cas9 system, we show that the Flag-tagged or untagged CENP-A K124R mutant is lethal. This lethality is rescued by monoubiquitin fusion, indicating that CENP-A ubiquitylation is essential for viability.

11.
Cell Mol Immunol ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511643

RESUMO

Interleukin-17A (IL-17A)-producing helper T (Th17) cells are a subset of CD4+ T cells that play important pathological roles in autoimmune diseases. Although the intrinsic pathways of Th17 cell differentiation have been well described, how instructive signals derived from the innate immune system trigger the Th17 response and inflammation remains poorly understood. Here, we report that mice deficient in REGγ, a proteasome activator belonging to the 11S family, exhibit significantly deteriorated autoimmune neuroinflammation in an experimental autoimmune encephalomyelitis (EAE) model with augmented Th17 cell polarization in vivo. The results of the adoptive transfer of CD4+ T cells or dendritic cells (DCs) suggest that this phenotype is driven by DCs rather than T cells. Furthermore, REGγ deficiency promotes the expression of integrin αvß8 on DCs, which activates the maturation of TGF-ß1 to enhance Th17 cell development. Mechanistically, this process is mediated by the REGγ-proteasome-dependent degradation of IRF8, a transcription factor for αvß8. Collectively, our findings delineate a previously unknown mechanism by which REGγ-mediated protein degradation in DCs controls the differentiation of Th17 cells and the onset of an experimental autoimmune disease.

12.
Molecules ; 24(19)2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547535

RESUMO

The aerial parts of Salvia miltiorrhiza Bunge, as the non-medicinal parts, are always discarded during harvesting, resulting in a huge waste of resources and environmental pressure. Due to the high flavonoid content and their antioxidant activities characteristics, the aerial parts of S. miltiorrhiza can be developed into natural antioxidants and used in foods. A high-speed counter-current chromatography (HSCCC) method, using a two-phase solvent system composed of tert-butyl methyl ether/n-butanol/acetonitrile/water (3:1:1:20, v/v), was the first to successfully isolate five flavonoids from the aerial parts of S. miltiorrhiza in one attempt, and separately categorized as rutin (1), isoquercitrin (2), kaempferol-3-O-α-l-rhamnopyranosyl-(1→6)-ß-d-glucopyranoside (3), kaempferol-3-O-ß-d-glucopyranoside (4) and apigenin-7-O-ß-d-glucopyranoside (5) after identification. The purities of these plant isolates were 97.3%, 99.5%, 92.8%, 98.1% and 98.7%, respectively. All the flavonoids were identified by HR-ESI-MS, 1D and 2D NMR. Compounds 3 and 5 were firstly isolated from the plant of S. miltiorrhiza. Results from antioxidant assays showed that rutin (1) and isoquercitrin (2) had higher antioxidant capacities compared to L-ascorbic acid as the positive control.

13.
J Food Prot ; 82(10): 1650-1654, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31524538

RESUMO

Bongkrekic acid (BKA) is a tricarboxylic fatty acid that inhibits adenine nucleotide translocase as a kind of mitochondrial toxins. BKA is produced by the bacterium Burkholderia gladioli pathovar cocovenenans. An investigation was performed to determine the source of possible BKA poisoning of a family in H City, Guangdong Province, People's Republic of China, who consumed a commercially produced rice noodle product that was not fermented or noticeably spoiled. Clinical and food samples were tested. BKA concentration was detected by liquid chromatography-tandem mass spectrometry. We isolated and identified the suspicious strains from the rice noodles and performed toxicity determination through an animal experiment. BKA detected in the cases and the dead dog was 2.15 to about 343 µg/kg. The cases and dead dog shared a unique history of food exposure. The BKA in the factory's food samples was 150 and 160 µg/kg. All mice given the BKA extract by gavage died within 24 h. In conclusion, the food poisoning was caused by the high BKA concentration of expired (4 days over the 24-h shelf life) wet rice noodle products, with corn and wheat starch contaminated by B. gladioli cocovenenans. Different from traditional BKA poisoning caused by fermented and spoiled corn or coconut products, there was no noticeable spoilage because of the nonfermentation process and overused sodium dehydroacetate. The risk of BKA in wet rice noodle products and application of antiseptics, such as sodium dehydroacetate, in such food should be quantitatively evaluated to prevent the recurrence of similar events.

15.
Carcinogenesis ; 2019 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-31400758

RESUMO

Hepatocellular carcinoma (HCC) is reported to associate with abnormal expression of SCF E3 ubiquitin ligases. FBXW10, an F-box protein of the E3 ubiquitin ligases, was abnormally regulated in HCC patients. However, whether FBXW10 is associated with HCC has not yet been evaluated. Here, we analyzed the associations between overall survival and various risk factors in 191 HCC tissues. Univariate and multivariate analyses demonstrated that FBXW10 was an independent risk factor related to HCC prognosis. The results showed that FBXW10, gender and tumor state were strongly associated with overall survival in HCC patients. Furthermore, high expression of FBXW10 was associated with poor survival among male HCC patients but not female HCC patients. FBXW10 was more highly expressed in male HCC tissues and more strongly related to vascular invasion in male HCC patients. Consistent with these findings, the male FBXW10-Tg(+) mice were more susceptible to tumorigenesis, changes in regenerative capacity, and liver injury and inflammation but not changes in liver function than FBXW10-Tg(-) mice. FBXW10 promoted cell proliferation and migration in HCC cell lines. Our findings reveal that FBXW10, an independent risk factor for HCC, promotes hepatocarcinogenesis in male patients, and is also a potential prognostic marker in male patients with HCC.

16.
J Biol Chem ; 294(42): 15293-15303, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31434741

RESUMO

The CD38 molecule (CD38) catalyzes biogenesis of the calcium-mobilizing messenger cyclic ADP-ribose (cADPR). CD38 has dual membrane orientations, and type III CD38, with its catalytic domain facing the cytosol, has low abundance but is efficient in cyclizing cytosolic NAD to produce cADPR. The role of cell surface type II CD38 in cellular cADPR production is unknown. Here we modulated type II CD38 expression and assessed the effects of this modulation on cADPR levels. We developed a photoactivatable cross-linking probe based on a CD38 nanobody, and, combining it with MS analysis, we discovered that cell surface CD38 interacts with CD71. CD71 knockdown increased CD38 levels, and CD38 knockout reciprocally increased CD71, and both could be cocapped and coimmunoprecipitated. We constructed a chimera comprising the N-terminal segment of CD71 and a CD38 nanobody to mimic CD71's ligand property. Overexpression of this chimera induced a dramatically large decrease in CD38 via lysosomes. Remarkably, cellular cADPR levels did not decrease correspondingly. Bafilomycin-mediated blockade of lysosomal degradation greatly elevated active type II CD38 by trapping it in the lysosomes but also did not increase cADPR levels. Retention of type II CD38 in the endoplasmic reticulum (ER) by expressing an ER construct that prevented its transport to the cell surface likewise did not change cADPR levels. These results provide first and direct evidence that cADPR biogenesis occurs in the cytosol and is catalyzed mainly by type III CD38 and that type II CD38, compartmentalized in the ER or lysosomes or on the cell surface, contributes only minimally to cADPR biogenesis.

17.
Oncogene ; 38(35): 6241-6255, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31312026

RESUMO

Early growth response-1 (EGR1) is a transcription factor correlated with prostate cancer (PC) progression in a variety of contexts. For example, EGR1 levels increase in response to suppressed androgen receptor signaling or loss of the tumor suppressor, PTEN. EGR1 has been shown to regulate genes influencing proliferation, apoptosis, immune cell activation, and matrix degradation, among others. Despite this, the impact of EGR1 on PC metastatic colonization is unclear. We demonstrate using a PC model (DU145/RasB1) of bone and brain metastasis that EGR1 expression regulates angiogenic and osteoclastogenic properties of metastases. We have shown previously that FN14 (TNFRSF12A) and downstream NF-κB signaling is required for metastasis in this model. Here we demonstrate that FN14 ligation also leads to NF-κB-independent, MEK-dependent EGR1 expression. EGR1-depletion in DU145/RasB1 cells reduced both the number and size of metastases but did not affect primary tumor growth. Decreased EGR1 expression led to reduced blood vessel density in brain and bone metastases as well as decreased osteolytic bone lesion area and reduced numbers of osteoclasts at the bone-tumor interface. TWEAK (TNFSF12) induced several EGR1-dependent angiogenic and osteoclastogenic factors (e.g., PDGFA, TGFB1, SPP1, IL6, IL8, and TGFA, among others). Consistent with this, in clinical samples of PC, the level of several genes encoding angiogenic/osteoclastogenic pathway effectors correlated with EGR1 levels. Thus, we show here that EGR1 has a direct effect on prostate cancer metastases. EGR1 regulates angiogenic and osteoclastogenic factors, informing the underlying signaling networks that impact autonomous and microenvironmental mechanisms of cancer metastases.

18.
J Exp Bot ; 70(19): 5145-5156, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31270546

RESUMO

Hybrid lethality forms a reproductive barrier that has been found in many eukaryotes. Most cases follow the Bateson-Dobzhansky-Muller genetic incompatibility model and involve two or more loci. In this study, we demonstrate that a coiled-coil nucleotide-binding site leucine-rich repeat (CC-NBS-LRR) gene is the causal gene underlying the Le4 locus for interspecific hybrid lethality between Gossypium barbadense and G. hirsutum (cotton). Silencing this CC-NBS-LRR gene can restore F1 plants from a lethal to a normal phenotype. A total of 11 099 genes were differentially expressed between the leaves of normal and lethal F1 plants, of which genes related to autoimmune responses were highly enriched. Genes related to ATP-binding and ATPase were up-regulated before the lethal syndrome appeared; this may result in the conversion of Le4 into an active state and hence trigger immune signals in the absence of biotic/abiotic stress. We discuss our results in relation to the evolution and domestication of Sea Island cottons and the molecular mechanisms of hybrid lethality associated with autoimmune responses. Our findings provide new insights into reproductive isolation and may benefit cotton breeding.

19.
Clin Interv Aging ; 14: 905-913, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190776

RESUMO

Purpose: The prevalence of depression and the relationship between depression and kidney function and health-related quality of life (HRQOL) are not well understood in elderly patients with predialysis chronic kidney disease (CKD). This study aimed to evaluate the prevalence of depression and the association between depression and kidney function and HRQOL. Patients and methods: In this cross-sectional study, 1079 elderly participants with CKD were recruited at 32 clinical centers located within 26 cities throughout 24 provinces in China. Demographic information and laboratory analyses were collected. Symptoms of depression were assessed using the 15-item Geriatric Depression Scale (GDS-15). HRQOL was evaluated using the Kidney Disease Quality of Life-36 (KDQOL-36) instrument. Results: The prevalence of depression was 23.0%. The estimated glomerular filtration rate (eGFR) was negatively correlated with the GDS score whether it was treated as a categorical variable (r=-0.097, P=0.001) or as a continuous variable (r=-0.100, P=0.001). Marital status, education level, history of CVD and diabetes, CKD stage and proteinuria confirmed to be independent and significant predictors of depression in patients with CKD. Compared with CKD 1-2 patients, we observed an increase of 0.541 and 4.171 in the odds for developing depression in patients CKD 4 (odds ratio [OR] =1.541; P=0.031) and CKD 5 (odds ratio [OR] =5.171; P<0.001), respectively. We observed negative and significant correlations with the GDS score for the following components: PCS (r=-0.370, P<0.001), MCS (r=-0.412, P<0.001), burden of kidney disease (r=-0.403, P<0.001), symptoms and problems of kidney disease (r=-0.360, P<0.001) and effects of kidney disease (r=-0.355, P<0.001). Depression was an independent and significant predictor of all the subcomponents of the HRQOL. Conclusions: The prevalence of depression in elderly patients with CKD was high and was negatively correlated with kidney function. Depression had a major negative impact on HRQOL.


Assuntos
Depressão/epidemiologia , Qualidade de Vida , Insuficiência Renal Crônica/epidemiologia , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos Transversais , Diabetes Mellitus/epidemiologia , Feminino , Taxa de Filtração Glomerular , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Estudos Prospectivos , Fatores Socioeconômicos
20.
Mol Pharm ; 16(7): 2845-2857, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31244219

RESUMO

To achieve efficient drug delivery to the posterior segment of the eye via topical instillation, novel multifunctional nanocomposites were prepared by hybridizing dexamethasone disodium phosphate (DEXP)-loaded liposome (LP) glycylsarcosine (GS)-anchored layered double hydroxides (named DEXP-HSPC@LDH-GS) and then fully characterized. The nanocomposites exhibited sustained-release performance as well as prolonged precorneal retention ability. MTT assays showed that the nanocomposites were not cytotoxic to both human corneal epithelial cells (HCEpiC) and human conjunctival epithelial cells (HConEpiC) at an LDH concentration of 100 µg/mL. The DEXP-HSPC@LDH-GS nanocomposites showed superior in vitro permeability on the HConEpiC-cell-based model. In the case of HConEpiC cells, both clathrin-mediated endocytosis and active transport by the peptide transporter-1 (PepT-1) were involved in the internalization of the nanocomposites. Fluorescent images of frozen sections of ocular tissues suggested that the possible route for the delivery of doxorubicin hydrochloride (DOX)-labeled nanocomposites from the ocular surface to the back of the eye was a non-corneal pathway. Furthermore, in rabbit eyes, the hybrid nanocomposites displayed markedly higher drug concentration in choroid-retina tissue than other single nanocarriers, such as LPs and LDH. Besides, the results of the eye irritancy test showed that nanocomposite eye drops can be classified as nonirritant, which are suitable to be used as eye drops. In a word, multifunctional nanocomposites based on LPs and LDH could be used as promising vehicles for efficient noninvasive drug delivery to the posterior segment of the eye.

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