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1.
Nucleic Acids Res ; 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32239217

RESUMO

SIRT6 deacetylase activity improves stress resistance via gene silencing and genome maintenance. Here, we reveal a deacetylase-independent function of SIRT6, which promotes anti-apoptotic gene expression via the transcription factor GATA4. SIRT6 recruits TIP60 acetyltransferase to acetylate GATA4 at K328/330, thus enhancing its chromatin binding capacity. In turn, GATA4 inhibits the deacetylase activity of SIRT6, thus ensuring the local chromatin accessibility via TIP60-promoted H3K9 acetylation. Significantly, the treatment of doxorubicin (DOX), an anti-cancer chemotherapeutic, impairs the SIRT6-TIP60-GATA4 trimeric complex, blocking GATA4 acetylation and causing cardiomyocyte apoptosis. While GATA4 hyperacetylation-mimic retains the protective effect against DOX, the hypoacetylation-mimic loses such ability. Thus, the data reveal a novel SIRT6-TIP60-GATA4 axis, which promotes the anti-apoptotic pathway to prevent DOX toxicity. Targeting the trimeric complex constitutes a new strategy to improve the safety of DOX chemotherapy in clinical application.

2.
Mol Genet Genomics ; 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32239329

RESUMO

Basic helix-loop-helix (bHLH) gene family is a gene family of transcription factors that plays essential roles in plant growth and development, secondary metabolism and response to biotic and abiotic stresses. Therefore, a comprehensive knowledge of the bHLH gene family is paramount to understand the molecular mechanisms underlying these processes and develop advanced technologies to manipulate the processes efficiently. Ginseng, Panax ginseng C.A. Meyer, is a well-known medicinal herb; however, little is known  about the bHLH genes (PgbHLH) in the species. Here, we identified 137 PgbHLH genes from Jilin ginseng cultivar, Damaya, widely cultivated in Jilin, China, of which 50 are newly identified by pan-genome analysis. These 137 PgbHLH genes were phylogenetically classified into 26 subfamilies, suggesting their sequence diversification. They are alternatively spliced into 366 transcripts in a 4-year-old plant and involved in 11 functional subcategories of the gene ontology, indicating their functional differentiation in ginseng. The expressions of the PgbHLH genes dramatically vary spatio-temporally and across 42 genotypes, but they are still somehow functionally correlated. Moreover, the PgbHLH gene family, at least some of its genes, is shown to have roles in plant response to the abiotic stress of saline. These results provide a new insight into the evolution and functional differentiation of the bHLH gene family in plants, new bHLH genes to the PgbHLH gene family, and saline stress-responsive genes for genetic improvement in ginseng and other plant species.

3.
Adv Colloid Interface Sci ; 278: 102136, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32171897

RESUMO

Determining the equilibrium wetting states and exploring the conditions and mechanisms of the wetting state transition from the Cassie-Baxter (CB) state to the Wenzel (W) state (CB-W transition) have been a central topic in the study of superhydrophobic behavior on rough or textured surfaces. Although considerable progress has been made, some issues regarding this topic are still not completely understood. In this study, a systematic thermodynamic analysis has been performed to address several key issues related to this topic. Generalized theoretical expressions for determining the equilibrium wetting states (the threshold Young contact angle of the CB region) and evaluating the stability of the CB state (the energy barrier separating the CB and W states and the critical pressure for the CB-W transition) have been derived. Applying these expressions to four types of surfaces built with protrusions in paraboloid, truncated cone, inverted truncated cone and flat-top pillar shapes, the wetting equilibrium and resultant wetting states have been studied. The physical meanings of the threshold Young contact angle, the roles and mechanisms of the energy barrier and critical pressure in stabilizing the CB state have been discussed. Finally, a general guidance for achieving robust superhydrophobicity on the studied surfaces has been given.

4.
J Hazard Mater ; 392: 122496, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32193121

RESUMO

Poly(ionic liquid)s (PILs) are attractive for their various applications, but the use of porous PILs have rarely been reported in anionic pollutants removal via ion-exchange by column. Herein, we report a serial of crosslinked imidazolium-based mesoporous PILs with Cl- and Br- as anions for hexavalent chromium (Cr(VI)) and methyl orange (MO) removal. Among them, PDVIm-Cl-SCD, from the free-radical polymerization of a dicationic monomer (N,N'-methylene-bis(1-(3-vinylimidazolium)) chloride, DVIm-Cl) and further supercritical carbon dioxide drying (SCD), displayed a very high sorption capacity (328.2 mg g-1 at 25 °C) and excellent utilization of adsorption sites (UOA, 86.2%) towards Cr(VI), and an unprecedentedly high sorption capacity (1615.0 mg g-1 at 25 °C) with a UOA of 67.4% to MO. Moreover, PDVIm-Cl-SCD also exhibited a broad pH range, excellent regeneration and remarkable reusability. Regarding to Cr(VI) removal, the volume of saturated KCl aqueous used for regenerating the Cr(VI) saturated PDVIm-Cl-SCD column (7.5-9.5 mL) was much less than the volume of treated Cr(VI) solution (160-200 mL). For MO removal, the volume of saturated NaCl solution used for regenerating the MO saturated PDVIm-Cl-SCD column (10.5-13.5 mL) was also much less than the volume of treated MO solution (220-235 mL), implying the great potential of PDVIm-Cl-SCD in sustainable wastewater treatment.

5.
Anim Biotechnol ; : 1-10, 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32167419

RESUMO

Goat milk in some cases is less allergenic than cow milk, therefore, more people drink goat milk in the world, so it is necessary for us to improve the yield and quality of goat milk. Previous studies have shown that some genes are closely related to lactation. Ovarian cancer G protein-coupled 1 (OGR1) is a G protein-coupled receptor discovered recently. OGR1 is widely found in various tissues of organisms and is involved in cell skeleton reorganization, carcinogenesis, cell proliferation, and apoptosis by regulating multiple signaling pathways in cells. However, the modulating effect of OGR1 in lactation is still unknown. Therefore, the objective of this study is to investigate the function of OGR1 in goat mammary epithelial cells (GMECs). Flow cytometry, CCK8, EDU, enzyme-linked immunosorbent assay, and triglyceride test kit assays were performed and we found that OGR1 regulated Bcl-2/Bax ratio, Fas protein expression as well as the phosphorylation of AKT and mammalian target of rapamycin (mTOR). si-OGR1 could enhance the proliferation of GMECs by promoting G1/S phase progression and the synthesis of ß-casein and triglyceride. By contrast, OGR1 repressed GMECs proliferation and down-regulated the synthesis of ß-casein and triglyceride by blocking the PI3K/AKT/mTOR signaling pathway in GMECs.

6.
Small ; : e1907690, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32191389

RESUMO

Nano-photocatalysts are known for their ability to degrade pollutants or perform water splitting catalyzed by light. Being the key functional ingredients of current and future products, the potential of nano-photocatalysts releasing into the environment and causing unintended harm to living organisms warrants investigation. Risk assessment of these materials serves as an important step to allow safe implementation and to avoid irrational fear. Using TiO2 and g-C3 N4 as representative nano-photocatalysts, this study evaluates their hazard potential in zebrafish. Under simulated solar light, nano-photocatalysts up to 100 mg L-1 show no acute toxicity to zebrafish embryos due to the protection of chorions. The short-lived reactive oxygen species generated by nano-photocatalysts only exert injury to the hatched larvae at and above 50 mg L-1 . The input of solar energy, determined by the depth of water, irradiation time, and light intensity, greatly influences the toxicity outcome. Increasing concentrations of natural organic matters contribute positively to the hazard potential at 0-10 mg L-1 while gradually diminishing the hazardous effect above 10 mg L-1 . This study demonstrates the importance of nano-bio interactions and environmental exposure conditions in determining the safety profile of nano-photocatalysts.

7.
Oral Dis ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32125746

RESUMO

OBJECTIVES: To determine the prognostic significance of preoperative prognostic nutritional index (PNI) in patients with primary oral squamous cell carcinoma (OSCC) after ablative surgery. MATERIALS AND METHODS: A total of 333 patients from two tertiary referral centers were enrolled as training and validation cohorts. The PNI was calculated as 10× serum albumin (g/dL) + 0.005 × total lymphocyte number (per mm3 ), and its optimal cutoff value for patient stratification was identified by X-tile software. Cox's proportional regression analyses and receiver operating characteristic (ROC) curves were employed to identify prognostic factors and their predictive performance. RESULTS: The optimal cutoff value of PNI was 47.4. Patients with low PNI had significantly shorter overall (OS) and disease-free survival than those with high PNI. Moreover, multivariate regression analyses indicated that PNI was an independent prognostic factor for OS in the training (hazard ratio [HR], 2.267; 95% confidence interval [CI]:1.335-3.849; p = .002) and validation (HR, 2.247; 95% CI: 1.352-3.735; p = .002) cohorts. ROC analyses revealed similar or superior predictive performance of PNI as compared to other prognostic parameters. CONCLUSIONS: Our findings reveal that decreased preoperative PNI significantly associates with worse prognosis for patients with OSCC, which serves as a novel prognostic biomarker for OSCC.

8.
Int J Biol Macromol ; 153: 17-25, 2020 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-32119948

RESUMO

Poly-mannuronic acids (PMs) have been considered as great biodegradable polymers as a green carrier for the potential pesticide deliver. In this work, the response surface design and microwave-assisted degradation were employed to obtain the optimum extraction conditions (i.e., 81 °C, 4.1 h, acid concentration 17.65 g/L). Meanwhile, the Ugi multi-component reaction makes the PM to be amphiphilic, called Ugi-PM, which induces the aggregation in aqueous solution at the concentration of 0.0895 g/L. The corresponding chemical structure and thermal stability of PM and Ugi-PM were determined by the FTIR, 1H NMR and thermogravimetric analysis (TG). Furthermore, the construction of novel emulsion-based delivery system using synthetic Ugi-PM was explored to prepare the pesticide of λ-Cyhalothrin. Interestingly, with the Ugi-PM concentration at 0.5 wt%, the stability of the Ugi-PM emulsion and the sustainable release of λ-Cyhalothrin are better than other concentrations and our previous system without degradation (Ugi-Alg emulsion). It is possible that electrostatic repulsion and steric hindrance derived from the hydrophobic Ugi-PM can promote the stability and flexible structure may be the reason for excellent sustained release of Ugi-PM emulsions in the pesticide deliver. The above-mentioned preparation progress is an efficient way to provide a valuable pesticide formulation.

9.
Int J Mol Med ; 45(4): 1250-1260, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32124944

RESUMO

The problems caused by diabetes mellitus (DM) and its related complications are gaining increasing attention. In our previous study, the abnormal proliferation of small intestinal epithelial cells (IECs) were observed in diabetic mice. However, little is known regarding the potential underlying mechanism. In the present study, the abnormal proliferation of IECs in DM and the marked upregulation of metastasis associated lung adenocarcinoma transcript 1 (MALAT1) was observed. Additionally, knockdown of MALAT1 significantly reduced abnormal IESC proliferation in DM mice. Bioinformatics analysis and luciferase reporter assays revealed that microRNA (miR)­129­5p was directly targeted by MALAT1. Moreover, the results of the bioinformatics prediction and luciferase assays demonstrated that MALAT1 directly interacted with SRY­box 9 (SOX9). Furthermore, MALAT1 silencing was observed to attenuate the abnormal proliferation of IESCs through the SOX9­mediated WNT/ß­catenin signaling pathway. Knockdown of MALAT1 downregulated SOX9 expression by binding to miR­129­5p, thereby inhibiting the abnormal proliferation of IESCs via the WNT/ß­catenin signaling pathway.

10.
Adv Mater ; : e1907747, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32128925

RESUMO

Actively collecting the mechanical energy by efficient conversion to other forms of energy such as light opens a new possibility of energy-saving, which is of pivotal significance for supplying potential solutions for the present energy crisis. Such energy conversion has shown promising applications in modern sensors, actuators, and energy harvesting. However, the implementation of such technologies is being hindered because most luminescent materials show weak and non-recoverable emissions under mechanical excitation. Herein, a new class of heterojunctioned ZnS/CaZnOS piezophotonic systems is presented, which displays highly reproducible mechanoluminescence (ML) with an unprecedented intensity of over two times higher than that of the widely used commercial ZnS (the state-of-the-art ML material). Density functional theory calculations reveal that the high-performance ML originates from efficient charge transfer and recombination through offset of the valence and conduction bands in the heterojunction interface region. By controlling the ZnS-to-CaZnOS ratio in conjunction with manganese (Mn2+ ) and lanthanide (Ln3+ ) doping, tunable ML across the full spectrum is activated by a small mechanical stimulus of 1 N (10 kPa). The findings demonstrate a novel strategy for constructing efficient ML materials by leveraging interface effects and ultimately promoting practical applications for ML.

11.
PeerJ ; 8: e8837, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32219040

RESUMO

Trypophobia is a strong emotion of disgust evoked by clusters of holes or round objects (e.g., lotus seed pod). It has become increasingly popular and been studied since 2010s, mainly in the West and Japan. Considering this, trypophobia might be a modern emotion, and hence urbanization possibly plays key roles in trypophobia. To address this issue, we compared the degree of trypophobia between urban and less urban people in China. In an experiment, we asked participants about their degree of discomfort from trypophobic images. The results showed that trypophobia occurred in both groups, although the effect size was larger in urban than less urban people. Moreover, post-experimental interviews and post-hoc analyses revealed that older people in less urban area did not experience as much trypophobia. Our findings suggest that trypophobia links to urbanization and age-related properties.

12.
Plants (Basel) ; 9(3)2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32168804

RESUMO

: SPL (SQUAMOSA promoter binding protein-like) gene family is specific transcription factor in the plant that have an important function for plant growth and development. Although the SPL gene family has been widely studied and reported in many various plant species from gymnosperm to angiosperm, there are no systematic studies and reports about the SPL gene family in Panax ginseng C. A. Meyer. In this study, we conducted transcriptome-wide identification, evolutionary analysis, structure analysis, and expression characteristics analysis of SPL gene family in Panax ginseng by bioinformatics. We annotated the PgSPL gene family and found that they might involve in multiple functions including encoding structural proteins, but the main function were still focused on the binding function. The result showed that 106 PgSPL transcripts were classified into two clades - A and B, both of which respectively consisted of three groups. Besides, we profiled PgSPL transcripts' genotypic, temporal, and spatial expression characteristics. Furthermore, we calculated the correlation of PgSPL transcripts in the 14 tissues of a 4 years old ginseng and 42 farmers' cultivars farmers' cultivars of 4 years old ginsengs' roots with both results showing that SPL transcripts formed a single network, which indicated that PgSPLs inter-coordinated when performing their functions. What's more, we found that most PgSPL transcripts tended to express in older ginseng instead of younger ginseng, which was not only reflected in the expression of more types of SPL transcripts in older ginseng, but also in the higher expression of SPL transcripts in older ginseng. Additionally, we found that four PgSPL transcripts were only massively expressed in roots. According to PgSPL transcripts' expression characteristics, we found that PgSPL23-35 and PgSPL24-09 were most proper two transcripts to further study as ginseng age's molecular marker. These results provide the basis for further elucidation of the PgSPL transcripts' biological function in ginseng and ginseng genetics improvement and gene breeding in the future.

14.
Fitoterapia ; 142: 104499, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32058049

RESUMO

3-O-[(E)-4-(4-cyanophenyl)-2-oxobut-3-en-1-yl] kaempferol is a novel lead compound to discover anti-diabetic and anti-obesity drugs. The present study reported the scaffold hopping of the lead compound to obtain a new isoxazole derivative, C45, which has improved glucose consumption at the nanomolar level (EC50 = 0.8 nM) in insulin resistant (IR) HepG2 cells. Western blotting showed that C45 markedly enhanced the phosphorylation of AMPK (AMP-activated protein kinase) and reduced the levels of the gluconeogenesis key enzymes PEPCK (phosphoenolpyruvate carboxykinase) and G6Pase (glucose 6-phosphatase) in HepG2 cells. The potential molecular mechanism of C45 may be activation of the AMPK/PEPCK/G6Pase pathways. We concluded that C45 might be a valuable candidate to discover anti-diabetic drugs.

15.
Chemosphere ; 249: 126141, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32062211

RESUMO

Crude oil pollution can cause severe and long-term ecological damage and oil cleanup has become a worldwide challenge. Conventional treatment strategies like in-situ burning, manual skimmer and bioremediation were labor-intensive and time-consuming. The high viscosity of crude oil also posed difficulty for traditional absorbents. Herein, to address these limitations, we designed and fabricated a floating absorbent that was comprised of reduced graphene oxide (RGO), melamine sponge (MS), and a 3D-printed mounting platform. Through a facile one-pot hydrothermal method, graphene oxide (GO) was simultaneously reduced to RGO and loaded in MS (RGO-MS). The resulted RGO-MS composites possess desirable hydrophobicity/oleophilicity for oil absorption with a water contact angle of 122°. The effective light-to-heat conversion allowed the RGO-MS composite to absorb approximately 95 times its own weight of crude oil within 12 min under light irradiation. A 3D-printed mounting platform for RGO-MS composites was further fabricated to improve its applicability and allow easy retrieval. Taking advantages of the RGO's hydrophobicity/oleophilicity and photothermal property, the floating ability of MS, this study demonstrated the real-life applicability of RGO-MS composites for in-situ crude oil cleanup.

16.
Biomed Pharmacother ; 125: 109885, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32007917

RESUMO

BACKGROUND AND PURPOSE: Multidrug resistance (MDR) is a great challenge and obstacle in cancer treatment. It is a common problem in the treatment of acute myeloid leukemia (AML). Whether grape seed proanthocyanidin extract (GSPE) could reverse MDR in patients with AML is still unknown. The aim of this study was to investigate the MDR reverse ability of GSPE and its possible mechanism in vitro. MATERIALS AND METHODS: Human leukemia cell line HL-60 cells and HL-ADR cells were used. MTT assay were employed to identify the cytotoxic effects of different chemotherapeutic drugs and reverse ability of GSPE. Flow cytometry assays were used to verify the cell apoptosis induced by GSPE. MDR-related genes expression was tested by real-time polymerase chain reaction (Q-PCR). MDR-related protein expression was assessed by Western blotting assays. The genes and their related protein expression of multidrug resistance-associated protein 1 (MRP1), multidrug resistance protein 1 (MDR1) and lung resistance-related protein (LRP) were tested in this study. KEY RESULTS: We found that HL-60/ADR cells were resistant to a variety of chemotherapeutic drugs, including cytarabine (Ara-C), adriamycin (ADR), vincristine (VCR), daunorubicin (DNR), mitoxantrone (MTZ), pirarubicin (THP), homoharringtonine (HHT) and etoposide (VP16). Co-treatment with GSPE could significant lower the IC50 of Ara-C and ADR in HL-60/ADR cells (P < 0.01). MDR related mRNA and their protein expression of MRP1 and MDR1 were significant highly expressed in HL-60/ADR cells than HL-60 cells (P < 0.01). But only protein expression of LRP was higher in HL-60/ADR cells than HL-60 cells (P < 0.05). GSPE could induce a higher intracellular level of ADR in HL-60/ADR cells. It could also inhibit Akt phosphorylation resulted in the down regulation of MRP1, MDR1 and LRP and induce cell apoptosis. 25.0 µg/mL GSPE significant inhibited the Akt phosphorylation (P < 0.05). CONCLUSION AND IMPLICATIONS: GSPE-reversed MDR of HL-60/ADR cells might be associated with the inhibition of the PI3K/Akt signaling pathway, which resulted in the down-regulation the expression of MRP1, MDR1 and LRP. These results provide that GSPE may serve as a combination therapy in AML chemotherapy for future study.

17.
eNeuro ; 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32015097

RESUMO

A fundamental challenge in studying principles of organization used by the olfactory system to encode odor concentration information has been identifying comprehensive sets of activated odorant receptors (ORs) across a broad concentration range inside freely behaving animals. In mammals, this has recently become feasible with high-throughput sequencing-based methods that identify populations of activated ORs in vivo In this study, we characterized the mouse OR repertoires activated by the two odorants, acetophenone and 2,5-dihydro-2,4,5-trimethylthiazoline, from 0.01% to 100% (v/v) as starting concentrations using phosphorylated ribosomal protein S6 capture followed by RNA-Seq. We found Olfr923 to be one of the most sensitive ORs that is enriched by acetophenone. Using a mouse line that genetically labels Olfr923-positive axons, we provided evidence that acetophenone activates the Olfr923 glomeruli in the olfactory bulb. Through molecular dynamics stimulations, we identified amino acid residues in the Olfr923 binding cavity that facilitate acetophenone binding. This study sheds light on the active process by which unique OR repertoires may collectively facilitate the discrimination of odorant concentrations.Significance Statement The ability of animals to discriminate odors over a range of odor concentrations while recognizing concentration-invariant odor identity presents an encoding challenge for the olfactory system. To further our understanding on how animals sense odors at different concentrations, it is important to describe how odor concentration information is represented at the receptor level. Here, we establish a sensitive in vivo approach to screen populations of odorant receptors enriched in the odor-activated sensory neurons in mice. We identified comprehensive lists of enriched odorant receptors against a 10,000-fold concentration range for two odorants. Describing the concentration-dependent activation for unique populations of odorant receptors is fundamental for future studies in determining how individual odorant receptors contribute to olfactory sensitivity and odor intensity coding.

18.
Int Angiol ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32052947

RESUMO

BACKGROUND: Insomnia may affect vascular factors and promote arteriosclerosis. Microparticles (MPs) are a heterogeneous group of bioactive small vesicles that can be found in blood and body fluids following activation, necrosis or apoptosis of virtually any eukaryotic cells. MPs are believed to participate in the pathogenesis of atherosclerosis. Few studies have been concerned with the microparticle level in patients with sleep disorder. The purpose of the present study is to measure the levels of endothelial microparticles (EMPs), platelet microparticles (PMPs) and leukocyte-derived microparticles (LMPs) in middle-aged and elderly patients with or without insomnia. METHODS: Patients with insomnia (n=30) and without insomnia (n=18) were enrolled. The insomnia group covered patients with chronic insomnia (n=16) and acute insomnia (n=14). Levels of EMPs (CD31 +, CD62E +) and PMPs (CD41a +, CD42a +) and granulocyte-derived (CD11a +) MPs were measured. Flow cytometry was performed on the Beckman Coulter analyzer. Reference gate was defined for the level of MPs using 0.22-0.45-0.88µm microspheres, and the size gate for MPs was 0.5-1.0µm. RESULTS: Of all types of MPs detected, the levels of CD31 +MPs, CD62E +MPs and CD11a +MPs were significantly higher in the insomnia group than in the non-insomnia group (P<0.05). Besides, compared with acute insomnia, the levels of CD31 + MPs and CD11a +MPs were significantly higher in chronic insomnia (P<0.001). CONCLUSIONS: In insomnia patients, atherosclerosis progression may be increased by the CD31+ EMPs-mediated apoptosis and endothelial injury. The level of CD11a+ LMPs kept increasing as insomnia persisted, which may indicate atherosclerosis progression.

19.
Food Funct ; 11(2): 1881-1890, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32068754

RESUMO

ß-Sitosterol is a natural compound widely found in many vegetable oils, nuts, and plant medicines; it lowers the cholesterol levels, enhances the production of plasminogen activators, and exhibits anticancer and antiatherogenic effects. However, the direct endothelial protection of ß-sitosterol against an oxidized low-density lipoprotein (ox-LDL) is not well understood. In the present study, ß-sitosterol significantly inhibited cell apoptosis (P < 0.01), increased cell migration (P < 0.01), improved energy metabolism (P < 0.05) and improved morphology after ox-LDL (50 µg ml-1) exposure following ß-sitosterol (2 µg mL-1) treatment in human aortic endothelial cells (HAECs ). A total of 691 differentially expressed (DE) mRNAs were identified (579 were upregulated and 112 were downregulated, fold change ≥2.0, P < 0.05) after 24 h of ß-sitosterol administration in transcriptome sequencing (ß-sitosterol vs. ox-LDL), which suggested that ß-sitosterol reversed 62.32% change in mRNAs induced by ox-LDL. DE mRNAs are enriched mainly in focal adhesion, ribosomes, eukaryotic translation elongation, etc. Considering that one of the enrichment is 3'-UTR-mediated translational regulation, we explored DE microRNA (miRNA). The miRNA-seq data proposed 87 up-regulated and 58 down-regulated miRNAs (fold change ≥2.0, P < 0.05) in miRNA-seq (ß-sitosterol vs. ox-LDL), suggesting that ß-sitosterol reversed 76.67% change in miRNAs induced by ox-LDL. The DE miRNA-DE mRNA coexpression network focused on ribosomes, cell cycle, oxidative phosphorylation, PI3K-Akt signaling pathway, TNF signaling pathway, ErbB signaling pathway, and mTOR signaling pathway. Consequently, miRNAs might be the targets of ß-sitosterol and play vital roles in transcriptional regulation in endothelial protective and antiatherogenic effects against ox-LDL.

20.
PLoS One ; 15(2): e0229497, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32101574

RESUMO

BACKGROUND: Previous studies have demonstrated that opioids are often prescribed and associated with complications in outpatients with cirrhosis. Less is known about opioids among hospitalized patients with cirrhosis. We aimed to describe the patterns and complications of opioid use among inpatients with cirrhosis. METHODS: This retrospective cohort study included adult patients with cirrhosis admitted to a single hospital system from 4/4/2014 to 9/30/2015. We excluded hospitalizations with a surgery, invasive procedure, or palliative care/hospice consult in order to understand opioid use that may be avoidable. We determined the frequency, dosage, and type of opioids given during hospitalization. Using bivariable and multivariable analyses, we assessed length of stay, intensive care unit transfer, and in-hospital mortality by opioid use. RESULTS: Of 217 inpatients with cirrhosis, 118 (54.4%) received opioids during hospitalization, including 41.7% of patients without prior outpatient opioid prescriptions. Benzodiazepines or hypnotic sleep aids were given to 28.8% of opioid recipients. In the multivariable model, younger age and outpatient opioid prescription were associated with inpatient opioids. Hospitalization was longer among opioid recipients (median 3.9 vs 3.0 days, p = 0.002) and this difference remained after adjusting for age, cirrhosis severity, and medical comorbidities. There was no difference in intensive care unit transfers and no deaths occurred. At discharge, 22 patients were newly started on opioids of whom 10 (45.5%) had opioid prescriptions at 90 days post-discharge. CONCLUSION: In non-surgical inpatients with cirrhosis, opioid prescribing was common and associated with prolonged length of stay. A high proportion of patients newly discharged with opioid prescriptions had ongoing prescriptions at 90 days post-discharge.

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