The combination of UCN-01 and ATRA triggers differentiation in ATRA resistant acute promyelocytic leukemia cell lines via RAF-1 independent activation of MEK/ERK.
Apr,
2019
With the introduction of arsenic trioxide and all-trans retinoic acid, the prognosis of acute promyelocytic leukemia has greatly improved. However, all-trans retinoic acid resistance is still unresolved in acute promyelocytic leukemia relapsed patients. In this study, the clinical achievable concentration of 7-hydroxystaurosporine synergized with all-trans retinoic acid to induce terminal differentiation in all-trans retinoic acid resistant acute promyelocytic leukemia cell lines. Though 7-hydroxystaurosporine is a PKC inhibitor, PKC might not be involved in the combination-induced differentiation since other PKC selective inhibitors, Gö 6976 and rottlerin failed to cooperate with all-trans retinoic acid to trigger differentiation. The combination significantly enhanced the protein level of CCAAT/enhancer binding protein β and/or PU.1 as well as activated MEK/ERK. U0126 (MEK specific inhibitor) not only suppressed the combination-induced differentiation but also restored the protein level of CCAAT/enhancer binding protein β and/or PU.1. However, RAF-1 inhibitor had no inhibitory effect on MEK activation and the combination-induced differentiation. Therefore, the combination overcame differentiation block via RAF-1 independent MEK/ERK modulation of the protein level of CCAAT/enhancer binding protein β and/or PU.1. These findings may provide a preclinical rationale for the potential role of this combination in the treatment of all-trans retinoic acid resistant acute promyelocytic leukemia patients. Подробнее
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
Core-shell nanomaterials: Applications in energy storage and conversion.
May,
2019
Materials with core-shell structures have attracted increasing attention in recent years due to their unique properties and wide applications in energy storage and conversion systems. Through reasonable adjustments of their shells and cores, various types of core-shell structured materials can be fabricated with favorable properties that play significant roles in energy storage and conversion processes. The core-shell material can provide an effective solution to the current energy crisis. Various synthetic strategies used to fabricate core-shell materials, including the atomic layer deposition, chemical vapor deposition and solvothermal method, are briefly mentioned here. A state-of-the -art review of their applications in energy storage and conversion is summarized. The involved energy storage includes supercapacitors, li-ions batteries and hydrogen storage, and the corresponding energy conversion technologies contain quantum dot solar cells, dye-sensitized solar cells, silicon/organic solar cells and fuel cells. In addition, the correlation between the core-shell structures and their performance in energy storage and conversion is introduced, and this finding can provide guidance in designing original core-shell structures with advanced properties. Подробнее
Advances in colloid and interface science
Upregulated KPNA2 promotes hepatocellular carcinoma progression and indicates prognostic significance across human cancer types.
Mar,
2019
Hepatocellular carcinoma (HCC) is one of the most aggressive cancers worldwide. Identification of the molecular mechanisms underlying the development and progression of HCC is particularly important. Here, we demonstrated the expression pattern, clinical significance, and function of Karyopherin α2 (KPNA2) in HCC. The expression of KPNA2 was upregulated in tumor tissue and negatively associated with the survival time, and a significant correlation between KPNA2 expression and aggressive clinical characteristics was established. Both in vitro and in vivo experiments demonstrated that knockdown of KPNA2 reduced migration and proliferation capacities of HCC cells, while over-expression of KPNA2 increased these malignant characteristics. The analysis of the Cancer Genome Atlas cohorts also reveals that high-KPNA2 expression is associated with poor outcome in multiple cancer types. In addition, gene sets enrichment analysis exhibited cell cycle and DNA replication as the top altered pathways in the high-KPNA2 expression group in HCC and other two cancer types. Overall, this study identified KPNA2 as a potential diagnostic and prognostic biomarker in HCC and other neoplasms, probably by regulating cell cycle and DNA replication. Подробнее
Acta biochimica et biophysica Sinica
Mechanical Performance of Warm-Mixed Porous Asphalt Mixture with Steel Slag and Crumb-Rubber⁻SBS Modified Bitumen for Seasonal Frozen Regions.
Mar,
2019
In this paper, the performance of a warm-mixed porous asphalt mixture (PAM) with steel slag as aggregate and crumb-rubber⁻SBS (styrene-butadiene-styrene) modified bitumen as a binder was studied. Two kinds of warming additives were used, namely ethylene bis stearic acid amide (EBS) and stearic acid amide (SA). The mixtures were investigated for their permeability, Marshall stability, low-temperature crack resistance, and underwent a rutting test, water sensitivity evaluation and Cantabro particle loss test. Then, the viscoelastic and dynamic characteristics of the mixtures were also analyzed. The results showed that the addition of the warming additives allowed the decrease of the manufacturing temperature by 10 °C. Thus, the addition of warming additives significantly improves the low-temperature crack resistance and slightly reduces the water sensitivity, weakly increases the permeability, and has little effect on the resilient modulus. Since the addition of SA significantly improves the low-temperature crack resistance and rutting resistance of the PAM, SA is therefore recommended for pavement engineering in seasonal frozen regions. Подробнее
Materials (Basel, Switzerland)
A Multi-Module Electrodynamic Exciter with a Variable Pole-Arc Ratio Disk Halbach Array for a High-Bandwidth Dynamic Torsional Stiffness Test.
Mar,
2019
In this paper, a multi-module electrodynamic exciter based on moving-magnet disk voice coil motor is presented to meet the demands of high torque and high bandwidth in a dynamic torsional stiffness test. A variable pole-arc ratio disk Halbach array (VPAR-DHA) is proposed, so that both high torque density and low rotor inertia can be obtained through enhancing the magnetic field in the working range. The analytical quasi-3-D model of VPAR-DHA was set up by using the harmonic function method, with the consideration of end-effects by a correction function. Electromagnetic structure optimization was carried out with the analytical model, and verified by 3-D finite-element (FEM) results. The proposed design was experimentally tested and verified with a prototype that achieved a peak dynamic torque output of 40 Nm at a frequency of 120 Hz, and a stroke of ±1°. The proposed method can also be easily extended to satisfy various demands of dynamic torsional stiffness test. Подробнее
Sensors (Basel, Switzerland)
Synthesis and Characterization of Flower-like Carbon-encapsulated Fe-C Nanoparticles for Application as Adsorbing Material.
Mar,
2019
Carbon-encapsulated Fe-C (Fe-C@C) nanoparticles with a divergently flower-like morphology were successfully synthesized for application as an adsorbing material by using freeze-drying and chemical vapor deposition (CVD) methods. The Fe metallic source was first loaded onto a sodium chloride (NaCl) supporter via freeze-drying to obtain the Fe/NaCl composite powder. Then, Fe-C@C nanoparticles were synthesized in the temperature range of 300⁻450 °C via CVD of acetylene in the Fe/NaCl composite powder using Fe nanoparticles as catalysts and NaCl as supporters. Because the NaCl supporter is water-soluble, the synthesized Fe-C@C nanoparticles were easy to purify, and a high purity was obtained by simple washing and centrifugation. The optimal Fe-C@C nanoparticles, synthesized at 400 °C, possessed a unique divergently flower-like structure and a high specific surface area of 169.4 m²/g that can provide more adsorption sites for contaminants. Adsorption experiments showed that the flower-like Fe-C@C adsorbent exhibited high adsorption capacity (90.14 mg/g) and fast removal of methylene blue (MB). Moreover, the magnetic properties of the nanoparticles, with saturation magnetization of 36.544 emu/g, facilitated their magnetic separation from wastewater. Therefore, the novel flower-like Fe-C@C nanoparticles with integrated adsorptive and magnetic properties have the potential to be an effective adsorbent in dye wastewater treatment. Подробнее
Materials (Basel, Switzerland)
Relevance Proof of Safety Culture in Coal Mine Industry.
03,
2019
This paper intends to use data to verify the correlation between safety culture, safety management system and safety knowledge, safety awareness, and safety habits, which is the correlation between the various parts of the behavior safety "2-4" model. Due to data limitations, the results are limited to the study of safety culture related relationships in coal mining enterprises. This paper first designed a questionnaire containing 30 questions, of which 1⁻5 questions represent safety culture, 6⁻22 questions represent safety management system, and 23⁻30 questions represent safety knowledge, safety awareness and safety habits. Employees of 27 coal mining enterprises in Shandong, Henan, Hunan and other places in China were surveyed and sampled by stratified random sampling, and 1514 valid questionnaires were obtained. After item analysis and correlation analysis, and it was found that, within the data of 1514 questionnaires, the item total correlation coefficients of questions 6, 9, 19 and 28 were all less than 0.2, indicating that the identification degree of these four items was poor, which was deleted. Using the data analysis of the remaining 26 questions in the questionnaire, it was found that the relationship between safety culture and the safety management system, the safety management system and safety knowledge, and safety awareness and safety habits is moderately related; safety culture and safety knowledge, safety awareness and safety habits are weakly related. The conclusion shows that the safety culture directly affects the safety management system; the safety management system directly affects the safety knowledge, safety awareness and safety habits; the safety culture indirectly affects safety knowledge, safety awareness and safety habits. However, why the expected strong correlation is not achieved, and whether the same conclusion can be obtained if the data scale is expanded or other types of enterprises are added for questionnaire measurement, these are questions worthy of further study, which is also the author's next research content. Подробнее
International journal of environmental research and public health
Constructing magnetic and high-efficiency AgI/CuFeO photocatalysts for inactivation of Escherichia coli and Staphylococcus aureus under visible light: Inactivation performance and mechanism analysis.
Jun,
2019
Magnetic materials usually exhibit advanced performance in many areas for their easy separating and recycle ability. In this study, silver iodide/copper ferrite (AgI/CuFeO) catalysts with excellent magnetic property were successfully synthesized and characterized by a series of techniques. Two typical bacteria Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were applied to estimate the photocatalytic inactivation performance of obtained AgI/CuFeO catalysts. Results revealed that the AgI/CuFeO (12.5% AgI) composite could absolutely inactivate 3 × 10 CFU/mL E. coli and 2.7 × 10 CFU/mL S. aureus cells severally in 50 min and 40 min under visible light irradiation, which showed a much higher photo-disinfection activity than monomers. Transmission electron microscopy was used to study the biocidal action of this nanocatalyst, the results confirmed that the treated E. coli cells were damaged, the nanocatalyst permeated into cells and resulting in death of cells. Besides, it was found that the destruction of bacterial membrane together with substantial leaked potassium ion (K) which caused by the photo-generated reactive species superoxide radical (O) and holes (h) could be the direct disinfection principles. For a deep insight into practical applications, the influences of different catalyst concentrations and reaction pH were also taken into discussion in details. The overall results indicated the novel photocatalyst with strong redox capacity and outstanding reusability can be widely employed in bacteria elimination. Подробнее
The Science of the total environment
Potential role of the IL17RC gene in the thoracic ossification of the posterior longitudinal ligament.
May,
2019
The thoracic ossification of the posterior longitudinal ligament (T‑OPLL) can cause thoracic spinal stenosis, which results in intractable myelopathy and radiculopathy. Our previous whole‑genome sequencing study first reported rs199772854 in the interleukin 17 receptor C (IL17RC) gene as a potentially pathogenic loci for T‑OPLL. The aim of the present study was to examine the effects of the IL17RC gene rs199772854A site mutation on osteogenesis by establishing a model of osteogenic differentiation. IL17RC gene mutation site and wild‑type site mouse embryonic osteoblast (3T3‑E1) models were constructed in order to induce the differentiation of the cells into osteoblasts. Whether the mutation site causes the abnormal expression of the IL17RC gene and osteogenic markers was analyzed by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blot analysis. The IL17RC gene rs199772854A site mutation was demonstrated to play a biological role through the overexpression of its own gene, and also to significantly increase the expression levels of osteogenic markers. Furthermore, the mutation upregulated the expression of the key proteins, tumor necrosis factor receptor (TNFR)‑associated factor 6 (TRAF6) and nuclear factor (NF)‑κB, in the interleukin (IL)‑17 signaling axis. On the whole, the findings of this study suggest that the IL17RC gene rs199772854A loci mutation propels mouse embryonic osteoblasts towards osteogenic differentiation and may play an important role in the pathogenesis of T‑OPLL. The IL17RC gene may promote osteogenesis through the IL‑17 signaling pathway and may thus be involved in the process of ectopic osteogenesis in T‑OPLL. Подробнее
International journal of molecular medicine
Immunosuppressive effect of artemisinin and hydroxychloroquine combination therapy on IgA nephropathy via regulating the differentiation of CD4+ T cell subsets in rats.
May,
2019
Immunoglobulin A nephropathy (IgAN) is an autoimmune kidney disease with complex pathogenesis leading to end-stage renal damage. The crucial pathological characteristic in IgAN is IgA immune complexes deposition accompany with mesangial cell proliferation and mesangial matrix expansion. Artemisinin (ART) is isolated from traditional Chinese medicine Artemisia annua L. Hydroxychloroquine (HCQ) is a classical antimalarial drug used to treat autoimmune diseases. Both of them possess immunosuppressive, immunomodulatory and anti-inflammatory features. The aim of this study was to investigate the pharmacological effects of ART combined with HCQ (AH) and explore the underlying mechanisms in IgAN. In vivo, our results showed that AH could significantly improve kidney dysfunction, decrease mesangial matrix expansion as well as immune complexes in mesangial area visualized by H&E and PAS staining. The depositions of IgA immune complexes and complement 3 (C3) were obviously reduced after AH treatment by immunofluorescence. Interestingly, the morphology of kidney and spleen was significantly swelled but reverted by AH in IgAN rats. Further mechanistic study showed that the higher proportions of the Th2 and Th17 cells were reduced but the lower differentiation of Th1 and Treg cells subsets were promoted by AH. Taken together, this study demonstrated that there was an immunosuppressive effect of AH therapy on IgAN rats via regulating the differentiation of CD4+ T cell subsets, which provided an alternative approach for IgAN treatment. Подробнее
International immunopharmacology
Dietary carbohydrate intake, glycaemic index, glycaemic load and digestive system cancers: an updated dose-response meta-analysis.
05,
2019
Several studies analysed the associations between dietary carbohydrate intake, glycaemic index (GI) and glycaemic load (GL) and digestive system cancers; however, the results remain controversial. This study was to perform a meta-analysis evaluating the quantitative and dose-response associations between carbohydrate intake, GI and GL, and risk of digestive system cancers. We searched medical and biological databases up to June 2018 and identified twenty-six cohort studies and eighteen case-control studies. Meta-analytic fixed or random effects models were applied to process data. We also performed dose-response analysis, meta-regression and subgroup analyses. We found that high levels of GI were significantly associated with the risk of digestive system cancers at the highest compared with the lowest categories from cohort studies (summary relative risk (RR)=1·10, 95 % CI 1·05, 1·15). Similar effects were observed from case-control studies of the comparison between the extreme categories, but the difference did not reach statistical significance (summary OR=1·28, 95 % CI 0·97, 1·69). We also observed significant dose-response association between GI and digestive system cancers, with every 10-unit increase in GI (summary RR=1·003; 95 % CI 1·000, 1·012 for cohort studies; summary OR=1·09; 95 % CI 1·06, 1·11 for case-control studies). In addition, both cohort studies and case-control studies indicated that neither dietary carbohydrate intake nor GL bore any statistical relationship to digestive system cancers from the results of the highest compared with the lowest categories analyses and dose-response analyses. The results suggest a moderate association between high-GI diets and the risk of digestive system cancers. Подробнее
The British journal of nutrition
A cyanide-sensing detector in aqueous solution based on anion-π interaction-driven electron transfer.
Mar,
2019
A "turn on" fluorescent and colorimetric sensor, HAT(CN)6, was developed for the light-up detection of cyanide. It was implemented through its strong anion-π interaction, inducing thermal CN- → HAT(CN)6 electron transfer, to give the dianion product [HAT(CN)6]2-, which exhibits unexpected fluorescence. The sensor shows high selectivity, rapid response and a low detection limit towards CN- in aqueous solution, hence indicating its enormous potential in practical applications. Подробнее
The Analyst
Bridging the Gap between Advancements in the Evolution of Diagnosis and Treatment towards Better Outcomes in Achalasia.
2019
Over the past few decades, there was an encouraging breakthrough in bridging the gap between advancements in the evolution of diagnosis and treatment towards a better outcome in achalasia. The purpose of this review is to provide updated knowledge on how the current evidence has bridged the gap between advancements in the evolution of diagnosis and treatment of esophageal achalasia. The advent of high-resolution manometry and standardization based on the Chicago classification has increased early recognition of the disease. These 3 clinical subtypes of achalasia can predict the outcomes of patients, and the introduction of POEM has revolutionized the choice of treatment. Previous evidence has shown that laparoscopic Heller myotomy (LHM) and anterior fundoplication were considered the most durable treatments for achalasia. Based on the current evidence, POEM has been evolving as a promising strategy and is effective against all 3 types of achalasia, but the efficacy of POEM is based on short- and medium-term outcome studies from a limited number of centers. Types I and II achalasia respond well to POEM, LHM, and PD, while most studies have shown that type III achalasia responds better to POEM than to LHM and PD. In general, among the 3 subtypes of achalasia, type II achalasia has the most favorable outcomes after medical or surgical therapies. The long-term efficacy of POEM is still unknown. The novel ENDOFLIP measures the changes in intraoperative esophagogastric junction dispensability, which enables a quantitative assessment of luminal patency and sphincter distension; however, this technology is in its infancy with little data to date supporting its intraoperative use. In the future, identifying immunomodulatory drugs and the advent of stem cell therapeutic treatments, including theoretically transplanting neuronal stem cells, may achieve a functional cure. In summary, it is important to identify the clinical subtype of achalasia to initiate target therapy for these patients. Подробнее
BioMed research international
CD8+CD122+PD-1+ Tregs Synergize With Costimulatory Blockade of CD40/CD154, but Not B7/CD28, to Prolong Murine Allograft Survival.
2019
A transplanted organ is always rejected in the absence of any immunosuppressive treatment due to vigorous alloimmunity. However, continuously global immunosuppression with a conventional immunosuppressant may result in severe side effects, including nephrotoxicity, tumors and infections. Tregs have been widely used to inhibit allograft rejection, especially in animal models. However, it's well accepted that administration of Tregs alone is not satisfactory in immune-competent wild-type animals. Therefore, it's imperative to promote Treg therapies under the cover of other approaches, including costimulatory blockade. In the present study, we demonstrated that administration of -expanded CD8CD122PD-1 Tregs synergized with costimulatory blockade of CD40/CD154, but not B7/CD28, to prolong skin allograft survival in wild-type mice and to reduce cellular infiltration in skin allografts as well. Treg treatment and blockade of CD40/CD154, but not B7/CD28, also exhibited an additive effect on suppression of T cell proliferation and pro-inflammatory cytokine expression in skin allografts. Importantly, blocking B7/CD28, but not CD40/CD154, costimulation decreased the number of transferred CD8CD122PD-1 Tregs and their expression of IL-10 in recipient mice. Furthermore, it's B7/CD28, but not CD40/CD154, costimulatory blockade that dramatically reduced IL-10 production by CD8CD122PD-1 Tregs , suggesting that B7/CD28, but not CD40/CD154, costimulation is critical for their production of IL-10. Indeed, infusion of IL-10-deficient CD8CD122PD-1 Tregs failed to synergize with anti-CD154 Ab treatment to further prolong allograft survival. Our data may explain why blocking B7/CD28 costimulatory pathway does not boost IL-10-dependent Treg suppression of alloimmunity. Thus, these findings could be implicated in clinical organ transplantation. Подробнее
Frontiers in immunology
Antitumor activity of histone deacetylase inhibitor chidamide alone or in combination with epidermal growth factor receptor tyrosine kinase inhibitor icotinib in NSCLC.
2019
The study was performed to investigate the antitumor efficacy of histone deacetylase inhibitor (HDACi) chidamide alone or with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) icotinib in non-small cell lung cancer (NSCLC). The cell viability, cell cycle, apoptosis, protein expression, and the molecular mechanisms were explored among ten NSCLC cell lines with chidamide and icotinib alone or in combination, and further validated in xenograft models of nude mice. Chidamide significantly reduced the viability of A549, HCC827, HCC827IR (icotinib resistant) cells, increased the sensitivity of icotinib synergistically in EGFR-TKI resistant cell line, especially in H1975 cells. Chidamide alone or combined with icotinib induced cell cycle arrest by inhibiting the activation of RAS/MAPK, PI3K/AKT and/or JAK/STAT pathways, and caused apoptosis by activating caspase 3 and PARP. Chidamide alone or with icotinib suppressed β-catenin expression in HCC827, HCC827IR, and H1975 cells. The sensitivity of H1975 cells to icotinib was increased by chidamide through restoring E-cadherin expression. Furthermore, chidamide alone or in combination with icotinib inhibited HCC827IR and H1975 xenograft growth in athymic nude mice, respectively, with no appreciable side effects. Chidamide or combinating with icotinib exhibits antitumor activity in NSCLC cells, and has potential clinical implication for the treatment of NSCLC. Подробнее
Journal of Cancer
The Role of Polymorphisms in Genes of PI3K/Akt Signaling Pathway on Prostate.
2019
: Increasing evidence suggested that polymorphisms in genes of PI3K/Akt pathway were closely related to prostate cancer (PCa) risk. Nevertheless, these results are controversial and inconclusive. Here, we conducted a comprehensive updated meta-analysis and systematic review to precisely illustrate the association between polymorphisms in genes of PI3K/Akt signaling pathway and PCa risk. : The gene set of PI3K/Akt pathway was referenced from the Kyoto Encyclopedia of Genes and Genomes (KEGG) website. Relevant studies were identified by the systematically researching on PubMed, Web of Science and Google Scholar databases up to October 1, 2017. The odds ratios (ORs) with a corresponding 95% confidential intervals (95%CIs) were applied to test their associations. All the analyses were conducted by using Stata 12.0 (Stata Corporation, USA). : Finally, 38 articles comprising 62 case-control studies were enrolled for 13 polymorphisms in genes of PI3K/Akt pathway. However, overall results failed to present a positive association between polymorphisms in genes of PI3K/Akt pathway and PCa risk. Nevertheless, in the subgroup analysis by ethnicity, we identified that -rs1800795 polymorphism was associated with an increased risk of PCa for Caucasian individuals in dominant model (MM + MW vs. WW: OR = 1.245, 95%CI = 1.176-1.318, < 0.001). : Our work suggests that polymorphisms in genes of PI3K/Akt Signaling Pathway are not risk factor for PCa. Further well-designed studies with larger samples and precise designs are demanded to corroborate our findings. Подробнее
Journal of Cancer
Group A Streptococcus Subcutaneous Infection-Induced Central Nervous System Inflammation Is Attenuated by Blocking Peripheral TNF.
2019
Group A streptococcus (GAS) infection causes a strong inflammatory response associated with cytokine storms, leading to multiorgan failure, which is characterized as streptococcal toxic shock syndrome. However, little is known about GAS subcutaneous infection-mediated brain inflammation. Therefore, we used a bioluminescent GAS strain and reporter mice carrying firefly luciferase under transcriptional control of the nuclear factor-kappa B (NF-κB) promoter to concurrently monitor the host immune response and bacterial burden in a single mouse. Notably, in addition to the subcutaneous inoculation locus at the back of mice, we detected strong luminescence signals from NF-κB activation and increased inflammatory cytokine production in the brain, implying the existence of central nervous system inflammation after GAS subcutaneous infection. The inflamed brain exhibited an increased expression of glial fibrillary acidic protein and nicotinamide adenine dinucleotide phosphate oxidase components and greater microglial activation and blood-brain barrier (BBB) disruption. Furthermore, Fluoro-Jade C positive cells increased in the brain, indicating that neurons underwent degeneration. Peripheral tumor necrosis factor (TNF), which contributes to pathology in brain injury, was elevated in the circulation, and the expression of its receptor was also increased in the inflamed brain. Blockage of peripheral TNF effectively reduced brain inflammation and injury, thereby preventing BBB disruption and improving survival. Our study provides new insights into GAS-induced central nervous system inflammation, such as encephalopathy, which can be attenuated by circulating TNF blockage. Подробнее
Frontiers in microbiology
