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1.
Sci Total Environ ; 716: 137017, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32036136

RESUMO

How to attenuate water surfactant pollution using carbon nanomaterials (CNMs) has been gaining increasing research attention in recent years. However, how the composition of cationic surfactants and physicochemical properties of CNMs may affect cationic surfactant maximum removal efficiency (Refficiency-max) with minimal cost from the aqueous phase and the associated mechanisms remain largely unclear. To address this knowledge gap, we compared removal efficiency of three cationic surfactants including dodecyl dimethyl benzyl ammonium chloride (DDBAC), tetradecyl dimethyl benzyl ammonium chloride (TDBAC) and hexadecyltrimethylammonium bromide (CTAB) by various carbon nanotubes (CNTs), including pristine and OH- or COOH-functionalized multiwalled- (MWCNTs) and single-walled (SWCNTs) CNTs. The results showed that Refficiency-max of CTAB by pristine MWCNTs with an outer diameter OD < 8 nm is 50.36 ± 0.56%, while that by OH-MWCNTs with OD < 8 nm is merely 22.72 ± 0.21%. Surface area and porosity of CNTs strongly affect Refficiency-max of cationic surfactants. The MWCNTs with a smaller OD have a higher Refficiency-max than that with a larger one especially for CTAB, due to their larger surface area and porosity. Among various CNTs, SWCNTs is an ideal choice for removing cationic surfactants, especially for non-aromatic CTAB. Interestingly, for most cases, cationic surfactant removal by CNTs decreased when the amount of CNTs added exceeded a certain level, attributable to their aggregation. This implies that it is impossible to completely remove some cationic surfactants even when excess CNTs were added. The π-π bonding dominates over hydrophobic interaction in regulating cationic surfactant removal especially for those with aromatic structure. Aromatic cationic surfactants such as DDBAC and TDBAC can be removed more readily by CNTs than those without a benzene ring due to their strong π-π interactions. TDBAC has a longer hydrophobic chain relative to DDBAC, leading to a better removal efficiency by CNTs, due to stronger hydrophobic interaction.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32022372

RESUMO

The capability to maintain a constant system temperature is vital in nature, since it endows the system with enhanced lifetime. This trait also works for zinc-based batteries, because their cycle-life is limited by notorious zinc dendrite/accumulation, which are highly affected by the inhomogeneous distribution of temperature on electrode and relatively low mechanical strength of membrane. Herein, boron nitride nanosheets (BNNSs) with high mechanical strength serving as heat-porter are introduced onto a porous substrate to enable uniform deposition of zinc and further a zinc-based flow battery with long cycle-life. The results indicate that BNNSs can effectively adjust the deposited zinc from needle-like to French fries-like morphology, thus affording the battery with a stable performance for nearly 500 cycles at 80 mA cm -2 . Most importantly, an energy efficiency of above 80% can be obtained even at 200 mA cm -2 , which is by far the highest value ever reported among zinc-based flow batteries.

3.
Hum Gene Ther ; 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32027183

RESUMO

The incidence of type 2 diabetes mellitus (T2DM) has been increasing annually, which is a serious threat to human health. Fibroblast growth factor 21 (FGF21) is one of the most popular targets for the treatment of diabetes because it effectively improves glycolipid metabolism. In our experiment, hFGF21 was injected and stably expressed in the liver tissues of a rat T2DM model with lentivirus system. Based on clinical and histopathological examinations, islet cells were protected, liver tissue lesions were repaired for more than four months. Glucose metabolism and the histopathology were controlled perfectly when hFGF21 was stable expressed in partial liver of T2DM rats. The results showed that the liver tissue cell apoptosis were reduced, the lipid droplet content were decreased, the oxidative stress indexes were improved, the glycogen content were increased, and the islet cells were increased too. Besides, insulin sensitivity and glycogen synthesis related genes expression were increased, but cell apoptosis related genes caspase3 and NFκB expression were decreased. The effectiveness of results suggested that the method of injecting hFGF21 to liver was an worth-considered method to cure T2DM rats.

4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 350-353, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027302

RESUMO

Abstract  Chronic myelogenous leukemia (CML) is a hematological malignancy that seriously threatens the lives of patients. It was found that there are abnormal classic Wnt pathway, that is, Wnt/ß-catenin signaling pathways in CML cells, moreover, Wnt/ß-catenin signaling pathway is involved in the growth and proliferation of CML cells, and closely relates with the self-renewal ability of CML leukemic stem cells. This review summarizes the recent studies on the relationship between Wnt/ß-catenin signaling pathway and CML, and the researches on the targeting inhibition of Wnt/ß-catenin signaling pathway in CML treatment, thus to provide new ideas for the treatment of CML.

5.
Exp Ther Med ; 19(2): 1448, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32010321

RESUMO

[This corrects the article DOI: 10.3892/etm.2019.7995.].

6.
Sci Rep ; 10(1): 1616, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005948

RESUMO

Flowering is important for plant propagation and survival, and it is also closely related to human life. Identifying the molecular mechanisms underlying flower development is essential for plant improvement and breeding. Flower development is a complex physiological process that is regulated by multiple genes. LFY genes play important roles in the floral meristem transition and act as crucial integrators in regulating the floral gene network. Argyranthemum frutescens is an ornamental species cultivated for floral displays, yet little is known about molecular mechanisms driving its flower development. In this study, the LEAFY gene homologue, AfLFY, was identified and cloned from A. frutescens, and its role and expression patterns were characterized. Two distinct copies of AfLFY were found in the A. frutescens genome and both sequences contained a 1248 bp open reading frame that encoded 415 amino acids. The putative protein sequences have a typical LFY family domain. In addition, AfLFY was expressed at the highest levels in young leaves of the vegetative stage and in the shoot apical bud meristem of the reproductive stage. Phylogenetic analysis showed that AfLFY was most closely related to DFL from Chrysanthemum lavandulifolium. Subcellular localization studies revealed that AfLFY localized to the nucleus. Heterologous expression of AfLFY in transgenic tobacco plants shortened its period of vegetative growth, converted the lateral meristems into terminal flowers and promoted precocious flowering. In addition, transgenic plants exhibited obvious morphological changes in leaf shape. qRT-PCR analysis indicated that the expression levels genes related to flowering, FT, SOC1, and AP1 were significantly upregulated in AfLFY transgenic plants. Our findings suggested that the AfLFY gene plays a vital role in promoting flowering and leaf development in A. frutescens. These results laid a foundation for us to understand the mechanism of AfLFY in regulation flowering, and the results will be helpful in improving A. frutescens through molecular breeding.

7.
Pharmacogenomics J ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32042095

RESUMO

Diffuse Large B-cell Lymphoma (DLBCL), a heterogeneous disease, is influenced by complex network of gene interactions. Most previous studies focused on individual genes, but ignored the importance of intergenic correlations. In current study, we aimed to explore the association between gene networks and overall survival (OS) of DLBCL patients treated with CHOP-based chemotherapy (cyclophosphamide combination with doxorubicin, vincristine and prednisone). Weighted gene co-expression network analysis was conducted to obtain insights into the molecular characteristics of DLBCL. Ten co-expression gene networks (modules) were identified in training dataset (n = 470), and their associations with patients' OS after chemotherapy were tested. The results were validated in four independent datasets (n = 802). Gene ontology (GO) biological function enrichment analysis was conducted with Metascape. Three modules (purple, brown and red), which were enriched in T-cell immune, cell-cell adhesion and extracellular matrix (ECM), respectively, were found to be related to longer OS. Higher expression of several hub genes within these three co-expression modules, for example, LCP2 (HR = 0.77, p = 5.40 × 10-2), CD2 (HR = 0.87, p = 6.31 × 10-2), CD3D (HR = 0.83, p = 6.94 × 10-3), FYB (HR = 0.82, p = 1.40 × 10-2), GZMK (HR = 0.92, p = 1.19 × 10-1), FN1 (HR = 0.88, p = 7.06 × 10-2), SPARC (HR = 0.82, p = 2.06 × 10-2), were found to be associated with favourable survival. Moreover, the associations of the modules and hub genes with OS in different molecular subtypes and different chemotherapy groups were also revealed. In general, our research revealed the key gene modules and several hub genes were upregulated correlated with good survival of DLBCL patients, which might provide potential therapeutic targets for future clinical research.

8.
Neuroscience ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32062019

RESUMO

Studies have shown that obesity-induced hyperglycemia and hyperlipidemia could cause increased hippocampal endoplasmic reticulum (ER) stress and impaired cognition-related proteins expression, resulting in learning and memory impairment. Meanwhile, aerobic exercise could activate hippocampal nuclear factor erythroid 2-related factor 2 (Nrf2) reducing ER stress. This study investigated the underlying molecular mechanisms of this effect. In order to clarify the relationship among ER stress, Nrf2 signaling and cognition-related proteins expression in vitro, we respectively treated hippocampal cells with high glucose and palmitic acid (PA), ER stress inhibitor 4-phenylbutyrate (4-PBA), and Nrf2 activator Tert-Butylhydroquinone (TBHQ). Results showed that the expression levels of glucose transporter 3 (GLUT3), fatty acid transport protein 1 (FATP1), ER stress biomarkers (GRP78, p-PERK, p-IRE1α and p-eIF2α), ER stress-mediated apoptosis biomarkers (caspase-12, CHOP and Bax/Bcl-2), and the activity of NLRP3-IL-1ß inflammatory pathway were significantly increased under high glucose and PA conditions, accompanied with depressed p38/ERK-CREB pathway and decreased levels of BDNF and SYN. On the other hand, both 4-PBA and TBHQ reduced ER stress and reversed the expression of the above-mentioned proteins. Our findings suggest that high glucose and PA could induce excessive ER stress and apoptosis via promoting the overexpression of GLUT3 and FATP1, and ER stress could suppress BDNF and SYN expression through negatively regulating p38/ERK-CREB pathway and positively regulating NLRP3-IL-1ß pathway, which could be reversed by activated Nrf2-HO-1 pathway.

9.
Bioorg Chem ; 96: 103638, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32062448

RESUMO

The dried fruits of Amomum tsao-ko are well-known dietary spices and traditional Chinese medicines. The random screen revealed that 50% ethanol-water extract of A. tsao-ko demonstrated significant α-glucosidase inhibitory activity with an IC50 value of 38.6 µg/mL. Bioactivity-guided isolation on the active fraction afforded 13 new 2,6-epoxy diarylheptanoids, tsaokopyranols A-M (1-13), and four known ones (14-17). Their structures featuring a 2,6-epoxy pyran ring were established by extensively spectroscopic analyses (HRESIMS, IR, UV, 1D and 2D NMR) and ECD calculations. Seven new (4-6, 8-11) and one known (16) compounds showed obvious α-glucosidase inhibitory activity with IC50 values ranging from 59.4 to 116.5 µM, higher than acarbose (IC50: 219.0 µM). An enzyme kinetic analysis indicated that compounds 12 and 13 were noncompetitive-type inhibitors of α-glucosidase with Ki values of 539.6 and 385.2 µM. This result provided new insights for the usage of A. tsao-ko, and 2,6-epoxydiarylheptanoids as new anti-diabetic candidates.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32062776

RESUMO

The consumption of rice contaminated with soil cadmium (Cd) threatens human health. It is essential to ensure the production of rice that meets food quality standards. Therefore, a large-scale field survey was conducted in Zhejiang province, southeastern China, to investigate the relationship between Cd accumulation in rice grains and Cd bioavailability in soil, and thus to establish a model to predict Cd contents in rice grains based on soil properties. For this purpose, a total of 156 paired rice and soil samples were collected. Pearson's correlation analysis revealed that Cd measurements obtained by diffusive gradient in thin films (DGT) had a higher correlation (r = 0.818, p < 0.001) with the Cd in rice grains as compared to the Cd measured by the DTPA, CaCl2, EDTA, and HCl extraction methods, which indicated that the DGT technique was a reliable method for the assessment of Cd bioavailability in soils. In addition, among the four extraction methods, the DTPA-extractable Cd showed the highest correlation with the Cd contents in rice grains. Therefore, we developed two predictive models (modelDGT and modelDTPA) to predict Cd levels in rice grains via Cubist multivariate mixed linear regression, using "soil DGT-measured Cd, pH, and oxide contents of Ca, Si, and Fe" or "soil DTPA-extractable Cd, pH, OM, and oxide contents of Ca and Fe" as explanatory variables, respectively. The overall modelDGT and modelDTPA had R2 values of 0.95 and 0.93, respectively, and relative error values of 0.30 and 0.33, respectively. Simple correlation analysis showed direct and close relationships between the measured Cd in rice grains and the Cd concentrations predicted by the Cubist modelDGT and modelDTPA, with R2 values of 0.979 and 0.922, respectively. Therefore, Cd levels in rice grains could be predicted very well based on the two prediction models, and thus, the two models derived in this study are effective in identifying soils in which the Cd in rice grains will exceed food safety standards, thereby helping to ensure safe rice production.

11.
Perit Dial Int ; 40(1): 84-92, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32063147

RESUMO

BACKGROUND: International Society for Peritoneal Dialysis guidelines recommend to routinely monitor the total measured clearance (mCl) of small solutes such as creatinine; however, collection of 24-h urine and peritoneal dialysis (PD) fluid is burdensome to patients and prone to errors. We hypothesized that equations could be developed to estimate mCl (estimated clearance (eCl)) using endogenous filtration markers. METHODS: In the Guangzhou PD Study (n = 980), we developed eCl equations using linear regression in two-third and validated them in the remaining one-third. Reference tests were mCl for urea nitrogen (UN) (mClUN, ml/min) and average mCl for UN and creatinine (mClUN-cr, ml/min/1.73 m2). Index tests were various eCl equations using UN, creatinine, low-molecular-weight proteins (LMWPs) (beta-trace protein (BTP), beta-2 microglobulin (B2M), and cystatin C), demographic variables, and body size. After reexpression of the equations in the combined data set, we analyzed accuracy (eCl within ± 2.0 units of mCl) and the predictive value of eCl to detect a weekly total standard Kt/V (weekly mClUN indexed for total body water) > 1.7 using receiver operating characteristic curve. RESULTS: Mean age of the cohort was 50 ± 15 years, 53% were male; mClUN was 6.9 ± 1.8 and mClUN-cr was 7.5 ± 2.8. Creatinine but not UN contributed to eCl for both mCl. LMWP did not improve accuracy for mClUN (range 88-89%). BTP and B2M improved the accuracy for mClUN-cr (82% vs. 80%); however, differences were small. The area under the curve for predicting a weekly Kt/V > 1.7 was similar for all equations (range 0.79-0.80). CONCLUSIONS: Total small solute clearance can be estimated moderately well in continuous ambulatory PD patients using serum creatinine and demographic variables without urine and dialysate collection.

12.
Artigo em Inglês | MEDLINE | ID: mdl-32005617

RESUMO

BACKGROUND: Candida auris can form long-lasting colonies in the hospital environment and on human skin. There is limited evidence regarding the efficacy of different methods and products for disinfecting hospitals and colonized patients to prevent the spread of C. auris. METHODS: The minimum inhibitory concentration of three disinfectant products ("84" disinfectant, IodineTincture disinfectant, and quaternary ammonium) and 75% ethanol against C. auris and other Candida species were measured. A pig skin model was used to evaluate the efficacy of three hand hygiene products in killing pathogens. The killing effect of ultraviolet-C (253.7 nm) and the LK/CXD bed unit ozone disinfection machine on C. auris was also evaluated. RESULTS: Thirty seconds of pig skin washing with bacteriostatic hand sanitizer followed by drying and 15 s of ethanol-based gel can completely eradicate the colonization of C. auris (3.00 log10 CFU). The antifungal activity of ultraviolet-C to C. auris inoculated on bed sheets was significantly reduced (P < 0.01) at a distance of 1 m. Candida glabrata and C. auris showed greater resistance to ozone than other Candida species. The ozone could completely eradicate C. auris (3.60 log10 CFU) on bed sheets at dosage of 300 mg/m3 for 40 min of exposure. CONCLUSIONS: We recommend extending the disinfection times of ultraviolet-C and ozone and emphasizing the effectiveness of washing skin with soap, drying skin, and then applying an ethanol-based gel to remove C. auris from skin.

13.
BMC Med Res Methodol ; 20(1): 18, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000690

RESUMO

BACKGROUND: With the increased empirical interest in the positive significance of improving nurses' sense of professional benefits, there is a requirement for measures of nurses' perceived professional benefit (NPPB). Our objective was to develop and psychometrically test a brief Nurses' Perceived Professional Benefit Questionnaire (NPPBQ). METHODS: After expert consultation and nurse interviews, a primary questionnaire was developed for an exploratory factor analysis (EFA). The seventeen items of the NPPBQ were used for verification of the theorized factor structure and content validity using a confirmatory factor analysis (CFA). The NPPBQ's concurrent validity was evaluated. Three samples of nurses were collected in Shanghai, Hangzhou and Nanjing between November 2017 and August 2018. RESULTS: The results of the EFA and CFA verified the five dimensions of nurses' occupational benefit discovery. The results demonstrated that the NPPBQ has adequate internal consistency and is fully consistent with the theorized factor structure. This 5-factor solution explained an adequate percentage of the total variance. The Cronbach's alpha of each dimension of the NPPBQ was good. The concurrent validity was significantly correlated with all aspects of the Maslach Burnout Inventory (MBI). CONCLUSION: The results suggest that the NPPBQ is a psychometrically sound measure for evaluating perceived professional benefits among a wide range of nurses.

14.
Nat Med ; 26(2): 259-269, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32042191

RESUMO

Developmental processes underlying normal tissue regeneration have been implicated in cancer, but the degree of their enactment during tumor progression and under the selective pressures of immune surveillance, remain unknown. Here we show that human primary lung adenocarcinomas are characterized by the emergence of regenerative cell types, typically seen in response to lung injury, and by striking infidelity among transcription factors specifying most alveolar and bronchial epithelial lineages. In contrast, metastases are enriched for key endoderm and lung-specifying transcription factors, SOX2 and SOX9, and recapitulate more primitive transcriptional programs spanning stem-like to regenerative pulmonary epithelial progenitor states. This developmental continuum mirrors the progressive stages of spontaneous outbreak from metastatic dormancy in a mouse model and exhibits SOX9-dependent resistance to natural killer cells. Loss of developmental stage-specific constraint in macrometastases triggered by natural killer cell depletion suggests a dynamic interplay between developmental plasticity and immune-mediated pruning during metastasis.

15.
J Hazard Mater ; 390: 122144, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-32006845

RESUMO

Many studies have examined changes in soil microbial community structure and composition by carbon nanomaterials (CNMs). Few, however, have investigated their impact on microbial community functions. This study explored how fullerene (C60) and multi-walled carbon nanotubes (M50) altered functionality of an agricultural soil microbial community (Archaea, Bacteria and Eukarya), using microcosm experiments combined with GeoChip microarray. M50 had a stronger effect than C60 on alpha diversity of microbial functional genes; both CNMs increased beta diversity, resulting in functional profiles distinct from the control. M50 exerted a broader, severer impact on microbially mediated nutrient cycles. Together, these two CNMs affected CO2 fixation pathways, microbial degradation of diverse carbohydrates, secondary plant metabolites, lipids and phospholipids, proteins, as well as methanogenesis and methane oxidation. They also suppressed nitrogen fixation, nitrification, dissimilatory nitrogen reduction, eukaryotic assimilatory nitrogen reduction, and anaerobic ammonium oxidation (anammox). Phosphorus and sulfur cycles were less vulnerable; only phytic acid hydrolysis and sulfite reduction were inhibited by M50 but not C60. Network analysis suggested decoupling of nutrient cycles by CNMs, manifesting closer and more hierarchical gene networks. This work reinforces profound impact of CNMs on soil microbial community functions and ecosystem services, laying a path for future investigation in this direction.

16.
Autophagy ; : 1-24, 2020 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-32019420

RESUMO

The precise mechanism through which macroautophagy/autophagy affects psoriasis is poorly understood. Here, we found that keratinocyte (KC) autophagy, which was positively correlated with psoriatic severity in patients and mouse models and could be inhibited by mitogen-activated protein kinase (MAPK) family inactivation. The impairment of autophagic flux alleviated psoriasisform inflammation. We also found that an autophagy-based unconventional secretory pathway (autosecretion) dependent on ATG5 (autophagy related 5) and GORASP2 (golgi reassembly stacking protein 2) promoted psoriasiform KC inflammation. Moreover, the alarmin HMGB1 (high mobility group box 1) was more effective than other autosecretory proteins in regulating psoriasiform cutaneous inflammation. HMGB1 neutralization in autophagy-efficient KCs eliminated the differences in psoriasiform inflammation between Krt14+/+-Atg5f/f KCs and Krt14Cre/+-atg5f/f KCs, and conversely, recombinant HMGB1 almost completely restored psoriasiform inflammation in Krt14Cre/+-atg5f/f KCs in vivo. These results suggest that HMGB1-associated autosecretion plays a pivotal role in cutaneous inflammation. Finally, we demonstrated that Krt14Cre/+-hmgb1f/f mice displayed attenuated psoriatic inflammation due to the essential crosstalk between KC-specific HMGB1-associated autosecretion and γδT cells. Thus, this study uncovered a novel autophagy mechanism in psoriasis pathogenesis, and the findings imply the clinical significance of investigating and treating psoriasis.Abbreviations: 3-MA: 3-methyladenine; ACTB: actin beta; AGER: advanced glycosylation end-product specific receptor; Anti-HMGB1: anti-HMGB1 neutralizing antibody; Anti-IL18: anti-IL18 neutralizing antibody; Anti-IL1B: anti-IL1B neutralizing antibody; ATG5: autophagy related 5; BAF: bafilomycin A1; BECN1: beclin 1; CASP1: caspase 1; CCL: C-C motif chemokine ligand; CsA: cyclosporine A; ctrl shRNA: lentivirus harboring shRNA against control; CXCL: C-X-C motif chemokine ligand; DCs: dendritic cells; DMEM: dulbecco's modified Eagle's medium; ELISA: enzyme-linked immunosorbent assay; EM: electron microscopy; FBS: fetal bovine serum; GORASP2 shRNA: lentivirus harboring shRNA against GORASP2; GORASP2/GRASP55: golgi reassembly stacking protein 2; GR1: a composite epitope between LY6 (lymphocyte antigen 6 complex) locus C1 and LY6 locus G6D antigens; H&E: hematoxylin and eosin; HMGB1: high mobility group box 1; HMGB1 shRNA: lentivirus harboring shRNA against HMGB1; IFNG/IFN-γ: interferon gamma; IL17A: interleukin 17A; IL18: interleukin 18; IL1A/IL-1α: interleukin 1 alpha; IL1B/IL-1ß: interleukin 1 beta; IL22/IL-22: interleukin 22; IL23A: interleukin 23 subunit alpha; IL23R: interleukin 23 receptor; IMQ: imiquimod; ITGAM/CD11B: integrin subunit alpha M; ITGAX/CD11C: integrin subunit alpha X; IVL: involucrin; KC: keratinocyte; KD: knockdown; KO: knockout; Krt14+/+-Atg5f/f mice: mice bearing an Atg5 flox allele, in which exon 3 of the Atg5 gene is flanked by two loxP sites; Krt14+/+-Hmgb1f/f: mice bearing an Hmgb1 flox allele, in which exon 2 to 4 of the Hmgb1 gene is flanked by two loxP sites; Krt14Cre/+-atg5f/f mice: keratinocyte-specific atg5 knockout mice generated by mating Atg5-floxed mice with mice expressing Cre recombinase under the control of the promoter of Krt4; Krt14Cre/+-hmgb1f/f mice: keratinocyte-specific hmgb1 knockout mice generated by mating Hmgb1-floxed mice with mice expressing Cre recombinase under the control of the promoter of Krt14; Krt14-Vegfa mice: mice expressing 164-amino acid Vegfa splice variant recombinase under the control of promoter of Krt14; LAMP1: lysosomal associated membrane protein 1; LDH: lactate dehydrogenase; LORICRIN: loricrin cornified envelope precursor protein; M5: TNF, IL1A, IL17A, IL22 and OSM in combination; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MKI67: marker of proliferation Ki-67; MTT: thiazolyl blue tetrazolium bromide; NFKB/NF-κB: nuclear factor kappa B; NHEKs: primary normal human epidermal keratinocytes; NS: not significant; OSM: oncostatin M; PASI: psoriasis area and severity index; PtdIns3K: class III phosphatidylinositol 3-kinase; qRT-PCR: quantitative RT-PCR; RELA/p65: RELA proto-oncogene, NF-kB subunit; rHMGB1: recombinant HMGB1; rIL18: recombinant interleukin 18; rIL1B: recombinant interleukin 1 beta; S100A: S100 calcium binding protein A; SQSTM1/p62: sequestosome 1; T17: IL17A-producing T; TCR: T-cell receptor; tcrd KO mice: tcrd (T cell receptor delta chain) knockout mice, which show deficient receptor expression in all adult lymphoid and epithelial organs; TLR: toll-like receptor; TNF/TNF-α: tumor necrosis factor; WOR: wortmannin; WT: wild-type; γδT17 cells: IL17A-producing γδ T cells.

17.
Biomed Pharmacother ; 125: 109870, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32032891

RESUMO

The increasing incidence rate and decreasing patients' five-year survival rate for endometrial cancer (EC) in recent decades highlight the necessity for further investigation of the molecular characteristics involved in cancer initiation and progression. In this study, we found that the pathways associated with mitotic cell cycle were enriched in primary EC samples versus normal endometrial samples through analyzing RNA-seq data of The Cancer Genome Atlas (TCGA). The messenger RNA (mRNA) expression of three activator E2Fs (E2F1, E2F2, and E2F3) and their target genes increased significantly in EC samples. Additionally, the high transcriptional activity of activator E2Fs was associated with poor survival, advanced clinical stage, high histologic grade, and aggressive histological type. We further demonstrated that E2Fs hyperactivation correlated with DNA hypomethylation and high cyclin-dependent kinase 4 (CDK4) expression. Moreover, abemaciclib, a selective CDK4 inhibitor, significantly inhibited the proliferation rates of human EC cell lines in vitro. And, abemaciclib also obviously inhibited EC cell growth in nude mice model. Collectively, our data suggest that the misregulation of CDK4/RB/E2Fs axis is associated with EC oncogenesis, and abemaciclib is a potential targeted drug for EC.

18.
Leuk Res ; 90: 106299, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-32035354

RESUMO

AIM: Large granular lymphocyte leukemia (LGLL) is a rare lymphoproliferative disorder associated with failure of hematopoiesis and autoimmune diseases. This study describes the clinical features and treatment responses of 108 patients with T-cell large granular lymphocyte leukemia (T-LGLL). METHODS: Clinical data were collected from T-LGLL patients treated at an anemia treatment center within the hematology and blood diseases unit of a single hospital from January 2009 to April 2019. RESULTS: The majority of patients (78 %) were symptomatic at the time of presentation. Splenomegaly was observed in 41 % of cases, while hepatomegaly and lymphadenopathy were rare (6 % and 7 %, respectively). Cyclosporine (CsA) monotherapy was used as first-line therapy for 16 patients, with an overall response rate (ORR) of 56 %. CsA in combination with steroids was administered in 83 patients, with an ORR of 48 %. Among patients experiencing relapse or resistance to first-line therapy, 10 received antithymocyte globulin (ATG) therapy, with an ORR of 50 %; an additional 9 patients received a modified regimen of high-dose cyclophosphamide (CTX) therapy, yielding an ORR of 78 %. CONCLUSIONS: This study provides new information regarding the clinical features and therapeutic strategies for T-LGLL, which can be used to improve clinical decision making for T-LGLL patients. The data presented here indicate the CsA is an effective option for the treatment of T-LGLL, while modified regimens of high-dose CTX or ATG are safe and effective choices for patients with CsA refractory disease.

19.
Trials ; 21(1): 77, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937335

RESUMO

BACKGROUND: Acupoint selection is a key factor in the treatment of diseases and has not been well studied. The aim of this trial is to explore the differences in efficacy between compatible acupoints and a single acupoint for patients with functional dyspepsia (FD). METHODS: This randomized controlled trial will be conducted in the First Affiliated Hospital of Changchun University of Chinese Medicine in China. Two hundred and sixteen FD patients will be randomly assigned to the compatible acupoints group, single acupoint group, or sham acupuncture group. This trial will include a 1-week baseline period, a 4-week treatment period, and a 4-week follow-up period. During the 4-week treatment period, patients will receive 20 sessions of acupuncture (weekly cycles of one session per day for 5 consecutive days followed by a 2-day break). The primary outcome will be a change in the Nepean Dyspepsia Life Quality Index from baseline to after the 4-week treatment period. Secondary outcome measures will include the dyspeptic symptom sum score, Overall Treatment Effect questionnaire, and 36-item Short Form survey. Adverse events also will be recorded. Ultraweak photon emission and metabolomics tests will be performed at baseline and at the end of treatment to explore the mechanisms of the differences between compatible acupoints and a single acupoint. DISCUSSION: The results of this trial will allow us to compare the difference in efficacy between compatible acupoints and a single acupoint. The findings from this trial will be published in peer-reviewed journals. TRIAL REGISTRATION: Acupuncture-Moxibustion Clinical Trial Registry, AMCTR-IPC-18000176, registered on 4 March 2019; Chinese Clinical Trial Registry, ChiCTR1900023983, registered on 23 June 2019.

20.
J Clin Pharm Ther ; 2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31954070

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Corticosteroids are recommended by almost all international guidelines for the management of exacerbations of chronic obstructive pulmonary disease (COPD). Nevertheless, due to their side effects, there are still concerns regarding the use of systemic corticosteroids (SCs). The Global Initiative for Chronic Obstructive Lung Disease guideline states nebulized budesonide (NB) may be a suitable alternative to SCs for treating COPD exacerbations. We conducted this study to systematically compare the efficacies of NB and SCs by using a meta-analysis. METHODS: PubMed, EMBASE and Cochrane Library databases were searched from database inception to 10 October 2019. Our main end points were change in pulmonary function and blood gas analysis. Secondary end points were numbers of exacerbations and hyperglycaemia. RESULTS AND DISCUSSION: Of 645 identified studies, 6 were eligible and were included in our analysis (N = 867 participants). Compared with SCs, NB was non-inferior on the change in FEV1 %predicted at 24 hours, 48-72 hours and 5-7 days; FEV1 at 5-7 days; FEV1 /FVC at 7 days. For blood gas analysis, our meta-analysis indicated that PaO2 , PaCO2 at 24 hours, 48-72 hours and 7-10 days and SaO2 at 24 hours and 7-10 days showed a non-significant difference in both groups, whereas the SaO2 was significant higher in NB group at 48-72 hours after treatment. Hyperglycaemia was less frequent with NB (odds ratio, 0.1; 95% CI, 0.01-0.85; P = .04). WHAT IS NEW AND CONCLUSION: Based on our meta-analysis, NB was not inferior to SCs when used in the treatment of COPD exacerbations. However, additional well-designed prospective studies are needed to identify the optimal dose of nebulized budesonide and the effects of nebulized budesonide in outpatients, or patients in ICU settings.

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