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1.
Plant Physiol Biochem ; 150: 140-150, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32142987

RESUMO

Peptide: N-glycanase (PNGase; EC 3.5.1.52) is a deglycosylation enzyme that is responsible for deglycosylating misfolded glycoproteins in the endoplasmic reticulum. However, the role of PNGase in plants is largely unknown. Here, we cloned and characterized the function of peptide: N-glycanase (CsPNG1) from cucumber. The amino acid encoded by CsPNG1 gene contained a typical transglutaminase (TGase) catalytic triad domain and belonged to the "TGase superfamily". Subcellular localization showed that CsPNG1 was located in the cell membrane and nucleus. Promoter sequence analysis and qPCR tests showed that CsPNG1 could respond to a variety of abiotic stresses and hormone treatments. Yeast one-hybrid assays revealed the interaction between the transcription factor CsGT-3b and CsPNG1 promoter. Importantly, overexpression of CsPNG1 in tobacco increased the tolerance to salt stress of transgenic plants. In addition, CsPNG1 interacted with CsRAD23 family proteins and the C-terminal UBA domain of CsRAD23 protein was responsible for binding to CsPNG1, indicating that CsPNG1 was involved in the ER-associated degradation pathway (ERAD). Taken together, our study demonstrated that CsPNG1 plays a positive role in improving plant salt tolerance, and these findings might provide a basis for further functional analysis of CsPNG1 genes in abiotic stress and ERAD.

2.
Food Chem ; 318: 126449, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32146306

RESUMO

Mulberry and chokeberry are rich sources of anthocyanins. In this study, the effect of the anthocyanin composition on the anthocyanin profile changes during in vitro digestion (mimicking the physiological conditions) was investigated by UHPLC-(ESI)-qTOF and UHPLC-(ESI)-QqQ. The antioxidant activity before and after in vitro digestion was elucidated. Cyanidin-3-O-glucoside and cyanidin-3-O-galactoside were dominant in mulberry and chokeberry, respectively. Moreover, the loss of cyanidin-3-O-galactoside in the chokeberry extract after digestion was greater than that of cyanidin-3-O-glucoside in the mulberry extract. After digestion, phenolic acids including protocatechuic acid and various cyanidin conjugates were newly formed because of decomposition and changes in the cyanidin-glycosides. The phenolic acid and cyanidin conjugate levels varied depending on the cyanidin glycoside sources in the colonic fraction. Finally, antioxidant activity before and after digestion was higher in the chokeberry extract than in the mulberry extract. Moreover, this activity continuously decreased until intestinal digestion but increased in the colonic fraction.

3.
Dig Dis Sci ; 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32157497

RESUMO

BACKGROUND: The personality traits of endoscopists have been suggested to affect the adenoma detection rate (ADR). We thus evaluated the relationship between endoscopists' personality traits and the ADR during colonoscopy using the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). METHODS: In total, 1230 patients (asymptomatic and aged 50-80 years) who underwent screening or surveillance (≥ 5 years) colonoscopy were recruited from 13 university hospitals by 20 endoscopists between September 2015 and December 2017. We retrospectively measured the ADR, polyp detection rate (PDR), and number of adenomas per colonoscopy (APC). All 20 endoscopists completed all 567 true/false MMPI-2 items. RESULTS: The overall mean colonoscopy withdrawal time, PDR, ADR, and APC were 7.3 ± 2.8 min, 55%, 45.3%, and 0.97 ± 1.58, respectively. No significant difference was observed in the MMPI-2 clinical scales (e.g., hypochondriasis and psychasthenia), content scales (e.g., obsessiveness and type A character), or supplementary scales (e.g., dominance and social responsibility) between the high ADR group (ADR ≥45%, n = 10) and the low ADR group (ADR < 45%, n = 10). In multivariate logistic regression analysis, the ADR was associated significantly with patient age and sex. The ADR was related significantly to endoscopists' colonoscopy experience and the per-minute increase in the colonoscopy withdrawal time (OR 1.21, 95% CI 1.06-1.38, p = 0.005). In a logistic regression analysis adjusted for patient factors, the ADR was associated significantly with ego strength (OR 1.04, 95% CI 1.00-1.09, p = 0.044), as measured by the MMPI-2. CONCLUSIONS: With the exception of ego strength, the endoscopists' personality traits were not associated with adenoma or polyp detection.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32162743

RESUMO

AIMS: His-Purkinje system pacing has been demonstrated as a synchronized ventricular pacing strategy via pacing His-Purkinje system directly, which can decrease the incidence of adverse cardiac structure alteration compared with right ventricular pacing (RVP). The purpose of this meta-analysis was to compare the effects of His-Purkinje system pacing and RVP in patients with bradycardia and cardiac conduction dysfunction. METHODS: PubMed, Embase, Cochrane Library, and Web of Science were systematically searched from the establishment of databases up to 15 December 2019. Studies on long-term clinical outcomes of His-Purkinje system pacing and RVP were included. Chronic paced QRS duration (QRSd), chronic pacing threshold, left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), all-cause mortality, and heart failure hospitalization were collected for meta-analysis. RESULTS: A total of 13 studies comprising 2,348 patients were included in this meta-analysis. Compared with RVP group, patients receiving His-Purkinje system pacing showed improvement of LVEF (mean difference [MD], 5.65; 95% confidence interval [CI], 4.38 to 6.92), shorter chronic paced QRS duration (MD, -39.29; 95% CI, -41.90 to -36.68), higher pacing threshold (MD, 0.8; 95% CI, 0.71 to 0.89) and lower risk of heart failure hospitalization (odds ratio [OR], 0.65; 95% CI, 0.44-0.96) during the follow-up. However, no statistical difference existed in LVEDV, LVESV and all-cause mortality between two groups. CONCLUSION: Our meta-analysis suggests that His-bundle pacing is more suitable for the treatment of patients with bradycardia and cardiac conduction dysfunction. This article is protected by copyright. All rights reserved.

5.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 42(1): 1-6, 2020 Feb 28.
Artigo em Chinês | MEDLINE | ID: mdl-32131933

RESUMO

Objective To investigate the effect of α-asarone on the function and expression of P-glycoprotein(P-gp)in rat brain microvascular endothelial cells(rBMECs). Methods rBMECs were exposed to L-glutamate(100 µmol/L) for 30 mins to induce the overexpression of P-gp/multidrug resistance gene 1a(Mdr1a)on the cell membranes,which mimicked the overexpression of P-gp/Mdr1a in blood brain barrier(BBB) when drug-resistant epilepsy attacked.MTT assay was used to detect the safe range of α-asarone concentration.The model cells were intervened with different concentrations of α-asarone at 12.5,25.0,and 50.0 µg/µl for 24 hours.After the treatment of α-asarone,the expression and the function of P-gp/Mdr1 were measured by Western blotting,real-time PCR,and intracellular rhodamine 123 accumulation assays. Results The rBMECs,stimulated by glutamine,showed a high expression of P-gp(F=1.924,P=0.020)/Mdr1a(F=1.788,P=0.019) compared to the normal rBMECs.The treatment with 25.0(F=1.924,P=0.025;F=1.788,P=0.017) and 50.0 µg/µl(F=1.924,P=0.035;F=1.788,P=0.026) α-asarone significantly depressed the expression of P-gp/Mdr1a.The treatment with 25.0 and 50.0 µg/µl α-asarone significantly increased intracellular accumulation of Rhodamine 123 by 40% and 60% respectively. Conclusions α-asarone down-regulates the high expressions of P-gp and Mdr1a mRNA in rBMECs induced by L-glutamate.Moreover and increases intracellular accumulation of rhodamine-123.Thus,α-asarone may reverse drug resistance in P-gp-mediated drug-resistant epilepsy.

6.
Eur J Immunol ; 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32135578

RESUMO

Exposure to diesel exhaust particles (DEPs) is associated with acute inflammatory responses in the lung and exacerbation of respiratory diseases. However, the mechanism by which DEPs trigger the inflammatory responses remains unclear. Here, we demonstrated that the interferon response factors IRF3 and IRF7 played pivotal roles in DEP-induced pulmonary inflammation. DEPs could not directly induce inflammatory cytokine expression in mouse cells, whereas DEPs triggered autophagy both in vitro and in vivo. The DEP-induced autophagy was augmented in the absence of IRF3 and IRF7, but not in the absence of IFNAR. The expression of Raptor was induced by IRF3 and IRF7 in response to DEPs treatment. Furthermore, administration of the mechanistic target of rapamycin (mTOR) inhibitor alleviated the inflammatory responses in the lung during DEP exposure. Our findings define an IFNAR-independent role of increased autophagy in the absence of IRF3 and IRF7 during pulmonary DEP exposure, and provide the basis to develop new therapeutic approaches to counteract the adverse effects of DEPs and possibly other ambient particulate matters. This article is protected by copyright. All rights reserved.

7.
Biomaterials ; 242: 119932, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32169772

RESUMO

Breast cancer contributes to high mortality rates as a result of metastasis. Tumor-derived exosomes facilitate the development of the premetastatic environment, interacting and inhibiting the normal function of immune cells, thereby forming an immunosuppressive microenvironment for tumor metastasis. Herein, the platelet and neutrophil hybrid cell membrane (PNM) was embellished on a gold nanocage (AuNC) surface called nanosponges and nanokillers (NSKs). NSKs can simultaneously capture and clear the circulating tumor cells (CTCs) and tumor-derived exosomes via high-affinity membrane adhesion receptors, effectively cutting off the connection between exosomes and immune cells. Bionic NSK is loaded with doxorubicin (DOX) and indocyanine green (ICG) for synergic chemo-photothermal therapy. NSKs show greater cellular uptake, deeper tumor penetration, and higher cytotoxicity to tumor cells in comparison to non-coated AuNCs or single-coated AuNCs in vitro. In vivo, the multipurpose NSKs could not only completely ablate the primary tumor but also inhibit breast cancer metastasis with high efficiency in xenograft and orthotopic breast tumor-bearing models. Thus, NSKs could be a promising nanomedicine for the future clinical intervention of breast cancer metastasis.

9.
Ann Rheum Dis ; 79(4): 518-524, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32114510

RESUMO

BACKGROUND: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterised by aberrant B cell hyperactivation, whose mechanism is partially understood. METHODS: We performed whole transcriptome sequencing of B cells from three pSS patients and three matched healthy controls (HC). Differentially expression genes (DEGs) were confirmed with B cells from 40 pSS patients and 40 HC by quantitative PCR and western blot. We measured the proliferation potential and immunoglobulins production of siRNA-transfected or plasmid-transfected B cells stimulated with cytosine-phosphate-guanine (CpG) or anti-IgM. We also explored Toll-like receptor 9 (TLR9) signalling to reveal the potential mechanism of B cell hyperactivation in pSS. RESULTS: We identified 77 upregulated and 32 downregulated DEGs in pSS B cells. We confirmed that epithelial stromal interaction (EPST1) expression in pSS B cells was significantly higher than that from HCs. EPSTI1-silencing B cells stimulated with CpG were less proliferated and produced lower level of IgG and IgM comparing with control B cells. EPSTI1-silencing B cells expressed lower level of p-p65 and higher level of IκBα, and B cells with overexpressed EPSTI1 showed higher level of p-p65 and lower level of IκBα. Finally, IκBα degradation inhibitor Dehydrocostus Lactone treatment attenuated p65 phosphorylation promoted by EPSTI1. CONCLUSION: Elevated EPSTI1 expression in pSS B cells promoted TLR9 signalling activation and contributed to the abnormal B cell activation, which was promoted by facilitating p65 phosphorylation and activation of NF-κB signalling via promoting IκBα degradation. EPSTI1 might be implicated in pSS pathogenesis and was a potential therapeutic target of pSS.

10.
Cell Signal ; : 109604, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32201331

RESUMO

Cardiovascular diseases (CVDs) have imposed a massive health and financial burden worldwide with high mortality and morbidity. However, the diagnostic value of current biomarkers might be impaired by a wide variety of noncardiac causes. Moreover, cardiovascular outcomes, survival, and prognosis of patients with CVDs remain poor despite advances in treatment. Therefore, novel diagnostic and therapeutic strategies are urgently required for timely identification of possible heart diseases in the early stage, which might effectively contribute to reducing the CVDs-caused morbidity and mortality. Circular RNA (circRNA) was initially identified as aberrant byproducts or abnormally spliced transcripts. However, with advances in bioinformatics and high-throughput sequencing technology, circRNAs has become an essential topic on a wide range of biological functions and emerged as novel players in diagnostic and therapeutic strategies for CVDs. In this article, we briefly introduce the biogenesis and functions of circRNAs. Moreover, we describe the roles of circRNAs in multiple CVDs, including atherosclerosis, coronary artery disease, myocardial infarction, as well as cardiomyopathy. In addition, we provide an overview on the current challenges and directions for further application.

12.
Artigo em Inglês | MEDLINE | ID: mdl-32043247

RESUMO

This study was performed to determine the effects of in vitro human digestion on the concentrations of five insecticides, namely 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (DDD), 2,2-bis(p-chlorophenyl)-1,1-dichloroethylene (DDE), bifenthrin, and fipronil. In vitro models included all the steps of human digestion, i.e., passage through the mouth, stomach, small intestine, and large intestine (with enteric bacteria). The concentrations of DDT and fipronil did not change (P > 0.05) until small intestinal digestion, whereas those of DDD, DDE, and bifenthrin decreased (P < 0.05) at each digestion step. The concentrations of all the insecticides decreased (P < 0.05) during the large intestinal digestion step with enteric bacteria, Lactobacillus sakei and Escherichia coli. In conclusion, the concentrations of all the tested insecticides decreased during all the steps of in vitro human digestion and were especially reduced by enteric bacteria during the large intestinal digestion step.

13.
Molecules ; 25(3)2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32019168

RESUMO

Baicalein, a widely-distributed natural flavonoid, exhibits antioxidative activity in mice with type-2 diabetes. However, the underlying mechanisms remain partially elucidated. In this study, we investigated the effect of baicalein on protein kinase R-like ER kinase (PERK)/nuclear factor erythroid-2-related factor 2 (Nrf2) pathway for the alleviation of oxidative stress and apoptosis. Human liver HL-7702 cells were stimulated with 60.5 mM of glucose to induce oxidative stress and treated with baicalein. The apoptosis was determined by fluorescence microscopy and flow cytometry. The regulation of the PERK/Nrf2 pathway by baicalein was determined by immunoblotting in both HL-7702 cells and liver tissues from diabetic mice. We found that baicalein significantly alleviated the oxidative stress and apoptosis in HL-7702 cells stimulated with glucose. Mechanistic studies showed that baicalein downregulated PERK and upregulated Nrf2, two key proteins involved in endoplasmic reticulum stress, in both HL-7702 cells and liver tissues from diabetic mice receiving baicalein treatment. Furthermore, the subcellular localization of Nrf2 and the regulation of downstream proteins including heme oxygenase-1 and CCAAT-enhancer-binding protein homologous protein (CHOP) by baicalein were also investigated. Our results suggest that the regulation of the PERK/Nrf2 pathway is one of the mechanisms contributing to the bioactivities of baicalein to improve diabetes-associated complications.

14.
Genetics ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32071193

RESUMO

The Transgenic RNAi Project (TRiP), a Drosophila melanogaster functional genomics platform at Harvard Medical School, was initiated in 2008 to generate and distribute a genome-scale collection of RNAi fly stocks. To date, the TRiP has generated >15,000 RNAi fly stocks. As this covers most Drosophila genes, we have largely transitioned to development of new resources based on CRISPR technology. Here, we present an update on our libraries of publicly available RNAi and CRISPR fly stocks, and focus on the TRiP-CRISPR overexpression (TRiP-OE) and TRiP-CRISPR knockout (TRiP-KO) collections. TRiP-OE stocks express sgRNAs targeting upstream of a gene transcription start site. Gene activation is triggered by co-expression of catalytically dead Cas9 (dCas9) fused to an activator domain, either VP64-p65-Rta (VPR) or Synergistic Activation Mediator (SAM). TRiP-KO stocks express one or two sgRNAs targeting the coding sequence of a gene or genes. Cutting is triggered by co-expression of Cas9, allowing for generation of indels in both germline and somatic tissue. To date, we have generated more than 5,000 CRISPR-OE or -KO stocks for the community. These resources provide versatile, transformative tools for gene activation, gene repression, and genome engineering.

15.
Eur J Med Chem ; 190: 112131, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32078861

RESUMO

Cryptic pockets, which are not apparent in crystallographic structures, provide promising alternatives to traditional binding sites for drug development. However, identifying cryptic pockets is extremely challenging and the therapeutic potential of cryptic pockets remains unclear. Here, we reported the discovery of novel inhibitors for striatal-enriched protein tyrosine phosphatase (STEP), a potential drug target for multiple neuropsychiatric disorders, based on cryptic pocket detection. By combining the use of molecular dynamics simulations and fragment-centric topographical mapping, we identified transiently open cryptic pockets and identified 12 new STEP inhibition scaffolds through structure-based virtual screening. Site-directed mutagenesis verified the binding of ST3 with the predicted cryptic pockets. Moreover, the most potent and selective inhibitors could modulate the phosphorylation of both ERK1/2 and Pyk2 in PC12 cells.

16.
Environ Pollut ; 261: 114162, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32078881

RESUMO

Di-(2-ethylhexyl) phthalate (DEHP), a plasticizer that is mainly used in the production of polyvinyl alcohol-containing chloride products, has attracted attention due to potential threats to human health and the environment. Nevertheless, knowledge of DEHP-induced nephrotoxicity is still limited. To explore the mechanism of DEHP-induced nephrotoxicity, quail were treated with 0, 250, 500 and 1000 mg/kg DEHP by oral gavage for 45 days. Based on the results of histopathological analysis, DEHP exposure induced a disorganized renal structure, a partially dilated glomerulus and an atrophied Bowman's space. Renal tubular epithelial cells were unclear, and swelling of columnar epithelial cells was observed, suggesting that DEHP exposure caused renal disease and renal injury. Notably, DEHP interfered with the homeostasis of cytochrome P450 systems (CYP450s) by increasing the activities or contents of CYP450s (total CYP450, Cyt b5, ERND, APND, AH and NCR). The expression levels of certain CYP450 isoforms (CYP1A, CYP1B, CYP2C, CYP2D, CYP2J and CYP3A) were significantly downregulated in the kidney in DEHP-treated quail. Furthermore, DEHP induced the expression of nuclear receptors (AHR, CAR and PXR) in a dose-dependent manner. The results of this study suggested that DEHP-induced nephrotoxicity in quail was associated with the induction of nuclear xenobiotic receptor (NXR) responses and interference with CYP450 homeostasis. In conclusion, all data indicated that DEHP induced nephrotoxicity by triggering NXRs and modulating the cytochrome P450 system. The results of this study provide a new basis for understanding the nephrotoxicity of DEHP.

17.
Pituitary ; 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32062801

RESUMO

PURPOSE: This study was designed to develop a computer-aided diagnosis (CAD) system based on a convolutional neural network (CNN) to diagnose patients with pituitary tumors. METHODS: We included adult patients clinically diagnosed with pituitary adenoma (pituitary adenoma group), or adult individuals without pituitary adenoma (control group). After pre-processing, all the MRI data were randomly divided into training or testing datasets in a ratio of 8:2 to create or evaluate the CNN model. Multiple CNNs with the same structure were applied for different types of MR images respectively, and a comprehensive diagnosis was performed based on the classification results of different types of MR images using an equal-weighted majority voting strategy. Finally, we assessed the diagnostic performance of the CAD system by accuracy, sensitivity, specificity, positive predictive value, and F1 score. RESULTS: We enrolled 149 participants with 796 MR images and adopted the data augmentation technology to create 7960 new images. The proposed CAD method showed remarkable diagnostic performance with an overall accuracy of 91.02%, sensitivity of 92.27%, specificity of 75.70%, positive predictive value of 93.45%, and F1-score of 92.67% in separate MRI type. In the comprehensive diagnosis, the CAD achieved better performance with accuracy, sensitivity, and specificity of 96.97%, 94.44%, and 100%, respectively. CONCLUSION: The CAD system could accurately diagnose patients with pituitary tumors based on MR images. Further, we will improve this CAD system by augmenting the amount of dataset and evaluate its performance by external dataset.

18.
Environ Res ; 182: 109105, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32069759

RESUMO

PURPOSE: The risk and protective factors of Internet gaming disorder (IGD) could vary by individual. The identification of more homogeneous subgroups may lead to better understanding of gaming behaviors and their consequences in adolescents. The purpose of this study was to investigate the prevalence of IGD among the subgroups defined by cluster analysis in adolescents. METHODS: A total of 2319 adolescents were enrolled in the Internet User Cohort for Unbiased Recognition of Gaming Disorder in Early Adolescence (iCURE) study at baseline. Self-reported IGD was assessed with a DMS-5 adapted measurement. Smartphone addiction, musculoskeletal discomfort, and dry eye symptoms were evaluated by self-administered questionnaires. Cluster analysis was performed using risk and protective factors of IGD after considering multicollinearity. RESULTS: Three different clusters were identified. Cluster 1 (19.2%) was users with combined potential psychological and social issues. Cluster 2 (32.3%) was users with potential social but no psychological issues. Cluster 3 (45.6%) was users with no potential issues of either a social or psychological nature. Adolescents from both clusters 1 and 2 showed higher degrees of IGD, smartphone addiction, musculoskeletal discomfort, and dry eye symptoms than did those from cluster 3. Also compared with adolescents in cluster 3, those in cluster 1 showed statistically higher risks of IGD (aOR:11.9, 95%CI:7.5-19.9), smartphone addiction (aOR:5.4, 95%CI:4.0-7.2), musculoskeletal discomfort (aOR:2.6, 95%CI:2.1-7.4), and dry eye symptoms (aOR:3.8, 95%CI:3.0-4.9). Those in cluster 2 also showed statistically higher risk of IGD, smartphone addiction, musculoskeletal discomfort, and dry eye symptoms compared with cluster 3 (aOR:4.5, 95%CI:2.8-7.6; aOR:2.8, 95%CI:2.1-3.7; aOR:1.6, 95%CI:1.3-1.9; and aOR:1.9, 95%CI:1.6-2.4, respectively). CONCLUSIONS: Clustering based on the risk and preventive factors of IGD may be suitable for determination of high risk of IGD in adolescents. However, we need to confirm the usefulness and clinical application of the classifications by observing their longitudinal changes.

19.
PLoS One ; 15(1): e0227587, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31923275

RESUMO

Diffusing fluid at a deep-sea hydrothermal vent creates rapid, acute physico-chemical gradients that correlate strongly with the distribution of the vent fauna. Two alvinocaridid shrimps, Alvinocaris longirostris and Shinkaicaris leurokolos occupy distinct microhabitats around these vents and exhibit different thermal preferences. S. leurokolos inhabits the central area closer to the active chimney, while A. longirostris inhabits the peripheral area. In this study, we screened candidate genes that might be involved in niche separation and microhabitat adaptation through comparative transcriptomics. The results showed that among the top 20% of overexpressed genes, gene families related to protein synthesis and structural components were much more abundant in S. leurokolos compared to A. longirostris. Moreover, 15 out of 25 genes involved in cellular carbohydrate metabolism were related to trehalose biosynthesis, versus 1 out of 5 in A. longirostris. Trehalose, a non-reducing disaccharide, is a multifunctional molecule and has been proven to act as a protectant responsible for thermotolerance in Saccharomyces cerevisiae. Putative positively selected genes involved in chitin metabolism and the immune system (lectin, serine protease and antimicrobial peptide) were enriched in S. leurokolos. In particular, one collagen and two serine proteases were found to have experienced strong positive selection. In addition, sulfotransferase-related genes were both overexpressed and positively selected in S. leurokolos. Finally, genes related to structural proteins, immune proteins and protectants were overexpressed or positively selected. These characteristics could represent adaptations of S. leurokolos to its microhabitat, which need to be confirmed by more evidence, such as data from large samples and different development stages of these alvinocaridid shrimps.

20.
Drug Deliv ; 27(1): 170-179, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31913724

RESUMO

Targeted nanocarriers have shown great promise in drug delivery because of optimized drug behavior and improved therapeutic efficacy. How to improve the targeting efficiency of nanocarriers for the maximum possible drug delivery is a critical issue. Here we developed L-carnitine-conjugated nanoparticles targeting the carnitine transporter OCTN2 on enterocytes for improved oral absorption. As a variable, we introduced various lengths of the polyethylene glycol linker (0, 500, 1000, and 2000) between the nanoparticle surface and the ligand (CNP, C5NP, C10NP and C20NP) to improve the ligand flexibility, and consequently for more efficient interaction with the transporter, to enhance the oral delivery of the cargo load into cells. An increased absorption was observed in cellular uptake in vitro and in intestinal perfusion assay in situ when the polyethylene glycol was introduced to link L-carnitine to the nanoparticles; the highest absorption was achieved with C10NP. In contrast, the linker decreased the absorption efficiency in vivo. As the presence or absence of the mucus layer was the primary difference between in vitro/in situ versus in vivo, the presence of this layer was the likely reason for this differential effect. In summary, the size of the polyethylene glycol linker improved the absorption in vitro and in situ, but interfered with the absorption in vivo. Even though this strategy of increasing the ligand flexibility with the variable size of the polyethylene glycol failed to increase oral absorption in vivo, this approach is likely to be useful for enhanced cellular uptake following intravenous administration of the nanocarriers.

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