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1.
Ultrason Sonochem ; 59: 104734, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31479886

RESUMO

Currently near-infrared (NIR) luminescence of lanthanide ions has received great attention because of their unique emissions in the near-infrared region (800-1700 nm). These NIR luminescent materials behave excellent applications in many fields such as sensors and probes in optical amplification, laser systems, biological systems and organic light-emitting diodes. In this work, two new near-infrared (NIR) emission three-dimensional (3D) YbIII and NdIII cluster-based coordination materials, namely {[Yb2(L)2(DMF)(H2O)4]·(DMF)2 (H2O)}n (NIR-MOF 1) and [Nd(L)(DMF)2]n (NIR-MOF 2) (H3L = terphenyl-3,4″,5-tricarboxylic acid) have been synthesized through the facile sono-chemical preparation methods. Both the near-infrared materials 1 and 2 have been characterized by single crystal X-ray diffraction, powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). Further the mixed-lanthanide near-infrared emission material Nd0.35Yb0.65L (NIR-MOF 3) can also be prepared under the sono-chemical conditions. NIR-MOF 3 can be successfully applied as the ratiometric NIR-MOF-based thermometer, which should origin from the emission intensity ratio between Yb3+ (976 nm) and Nd3+ (1056 nm) in the temperature range of 308-348 K. Besides these, the micro-morphologies of NIR-MOF 1 can be deliberately tuned through different sono-chemical reaction factors (reaction time, reaction temperature and sono-chemical powers). These tuned nano-sized materials NIR-MOF 1 (100 W, 80 min) can be utilized as the fluorescent sensing material to distinguish furazolidone and sulfasalazine from other antibiotics. At the same time, NIR-MOF 2 can be applied as the first example of MOFs-based sensors for discriminating l-arginine from other amino acids through the "turn-on" mode in the near-infrared emission region.

2.
Pest Manag Sci ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31486576

RESUMO

BACKGROUND: The effects of exposing Apis mellifera larvae to common insecticides were tested in the laboratory. RESULTS: The acute toxicity values of the four insecticides that we tested ranged from high toxicity to low toxicity: deltamethrin > cypermethrin > carbaryl > acetamiprid. The NOAEC (no observed adverse effect concentration) values of the chronic toxicity tests for each compound are 5 mg/L for acetamiprid, 2 mg/L for carbaryl, 1 mg/L for cypermethrin, and 0.2 mg/L for deltamethrin. CONCLUSION: According to the risk quotient (RQ) values of acute and chronic toxicity that we obtained, the risk is acceptable at exposure rates that have been identified in the field. Overall, our results are valuable for evaluating the acute and chronic toxicities of these insecticides to developing honey bees. This article is protected by copyright. All rights reserved.

3.
Biochimie ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31491441

RESUMO

ArgR, a transcriptional regulator belonging to the AraC/XylS family, plays a key role in arginine metabolism regulation. ArgR has also been found to repress the transcription of a lipase gene, but its molecular mechanism is still unknown. In this study, we investigated the molecular mechanism acting on the expression of intracellular lipase gene lipA regulated by ArgR in Pseudomonas protegens Pf-5 through knockout and overexpression of argR, detection of DNA-protein interaction in vivo, determining whole-cell lipase activities of various strains derived from Pf-5, and examining ß-galactosidase activities of various lacZ fusions. The results demonstrated that ArgR inhibits lipA expression at the transcriptional level. Further results showed that the inhibition of lipA transcription by ArgR is mediated by binding to the ArgR binding site of lipA promoter to produce steric hindrance, in which the common sequence, TGTCGC is crucial for the ArgR binding. Besides, arginine inhibits lipA expression in both wild-type and argR mutant, and shows a synergistic inhibition on lipA expression when combined with ArgR. To the best of our knowledge, this is the first report on ArgR directly repressing the transcription of lipase gene.

4.
Chin Med J (Engl) ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31490264

RESUMO

BACKGROUND: MicroRNAs (miRNAs) have played important roles in the regulation of gene expression in many cancers, but their roles in esophageal squamous cell carcinoma (ESCC) are still unclear. The aim of this study was to determine the potential ESCC-specific key miRNAs from a large sample dataset in The Cancer Genome Atlas (TCGA). METHODS: Integrative bioinformatics analysis was used to identify key ESCC-specific miRNAs related to the ESCC patients' tumor histological grade and lymphatic metastasis from TCGA. Next, these key miRNA potential gene regulatory functions and relationships with ESCC patients' clinical characteristics and overall survival were analyzed. Finally, three key miRNAs were selected randomly and quantificational real-time polymerase chain reaction (qRT-PCR) was used to validate in 51 newly diagnosed ESCC patients' tissues samples (collected from Nov. 2017 to Feb. 2019, in Wuwei, China) whether the bioinformatics analyses results were reliable and valid. Two-tailed Student's t test, Pearson chi-squared test and Kaplan-Meier survival analysis were used in this study. RESULTS: Thirty-five ESCC-specific miRNAs from TCGA database were investigated (fold-change > 2.0, P < 0.05), and 28 participated in the miRNAs-mRNAs co-expression network construction, while 17 were related with ESCC patients' tumor histological grade, TNM stage, and lymphatic metastasis (P < 0.05). Meanwhile, there were six miRNAs (including miR-200b-3p, miR-31-5p, miR-15b-5p, miR-141-3p, miR-135b-5p, and miR-195-5p) those were correlated with overall survival of ESCC patient (log-rank, P < 0.05). MiR-135b-5p, miR-15b-5p, and miR-195-5p were selected for verification of the expression levels in 51 ESCC patients' tissue samples by using qRT-PCR. We found that the fold-changes between qRT-PCR and TCGA were completely consistent. The results also suggested that miR-135b-5p, miR-15b-5p, and miR-195-5p were significantly correlated with tumor differentiation degrees (P < 0.05), miR-195-5p was significantly correlated with tumor TNM stage (P < 0.05), and miR-135b-5p was significantly correlated with lymph-node metastasis (P < 0.05). MiR-135b-5p, miR-15b-5p, and miR-195-5p expression levels, ESCC patient clinical features association analysis results and the aforementioned TCGA bioinformatics analyses were similar. CONCLUSION: This study identified key ESCC-related miRNAs. The key miRNAs are worthy of further investigation as potential novel biomarkers for diagnosis, classification, and prognosis of ESCC.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31479802

RESUMO

OBJECTIVES: The clinical effect of 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) may be correlated with the degree of dysplasia of cancer tissues, but much is still unknown regarding the differences in its effectiveness, especially in oral cancer and precancerous lesions. The aim of this study is to compare the effects of ALA-PDT on a human oral precancerous cell line (DOK) and an oral squamous cell carcinoma cell line (CAL-27). METHODS: First, we explored the dose- and time-dependent responses of DOK and CAL-27 cells to ALA-PDT. DOK and CAL-27 cells were incubated with various concentrations of ALA (from 0.25 to 2 mM), followed by PDT using laser irradiation at 635 nm. The resulting photocytotoxicity was assessed in both cell lines using MTT assays. Further, apoptosis was assessed using flow cytometry, reactive oxygen species (ROS) generation was evaluated with 2,7-dichlorofluorescein diacetate (DCFH2-DA), and the response to treatment was examined via RT-qPCR and Western blotting to measure the mRNA and protein expression levels of matrix metallopeptidase 2 (MMP-2) and MMP-9. RESULTS: ALA-PDT inhibited the proliferation of DOK and CAL-27 cells in a dose- and time-dependent manner. Dose-effect and inhibition-time relationships were also found. The rates of DOK and CAL-27 cell apoptosis when the ALA dose was 1 mM were 30.66 ± 3.10 % and 75.40 ± 1.29 %, respectively (P < 0.01). Following PDT, compared with DOK cells, the ROS level in CAL-27 cells was significantly increased and was correlated with an increase in the ALA concentration. Mechanistically, both the mRNA and protein expression levels of MMP-2 and MMP-9 were found to be regulated in both cell types after ALA-PDT. CONCLUSION: ALA-PDT effectively killed DOK and CAL-27 cells in a dose- and time-dependent manner in vitro. However, under the same conditions, the susceptibilities of these cell lines to ALA-PDT were different. Further studies are necessary to confirm whether this difference is present in clinical oral cancer and precancerous lesions.

6.
Artif Cells Nanomed Biotechnol ; 47(1): 3704-3710, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31514535

RESUMO

Cardiovascular disease is recognized as a leading cause of death worldwide, but the risk of death is 2-3 times higher for individuals with diabetes. NLRP3 inflammasome activation is a leading pathway of vascular damage, and new treatment methods are needed to reduce NLRP3 inflammasome expression, along with a detailed understanding of how those treatments work. In a series of assays on human vascular endothelial cells that were exposed to high concentrations of free fatty acids (FFA) to induce a diabetes-like environment, we found a significant impact of cilostazol, a vasodilator widely used to treat blood flow problems and well-tolerated medication. To our knowledge, this study is the first to demonstrate the effects of cilostazol in primary human aortic endothelial cells. We found that cilostazol significantly reduced NLRP3 inflammasome activation, as well as the activity of other related and harmful factors, including oxidative stress, expression of NADPH oxidase 4 (NOX-4), thioredoxin-interacting protein (TxNIP), high mobility group box 1 (HMGB-1), interleukin 1ß (IL-1ß) and IL-18. Cilostazol also protected the functionality of sirtuin 1 (SIRT1), which serves to restrict NLRP3 inflammasome activity, when exposure to FFAs would have otherwise impaired its function. Thus, it appears that cilostazol's mechanism of action in reducing NLRP3 inflammasome activation is an indirect one; it protects SIRT1, which then allows SIRT1 to perform its regulatory job. Cilostazol has potential as an already-available, well-tolerated preventive medication that may alleviate some of the adverse vascular effects of living with diabetes. The findings of the present study lay the groundwork for further research on the potential of cilostazol as a safe and effective treatment against diabetic endothelial dysfunction and vacular disease.

7.
Opt Express ; 27(16): 22138-22146, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31510507

RESUMO

Compressive sensing (CS) has been used in LiDAR systems utilizing one single-photon-counting avalanche diode. We demonstrate an unexpected grayscale inversed image of an object at an unchosen depth, which appears in the reconstruction of the infrared single-pixel LiDAR system due to the pile-up effect. A correction algorithm and the sparse measurement are proposed and experimentally verified to effectively reduce the photon pile-up influence, so that the negative images can be completely removed. The correction methods in this research can improve the accuracy and the flexibility of the single-pixel LiDAR systems employing detectors with a low maximum light count.

8.
J Infect Dis ; 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31504652

RESUMO

Staphylococcus aureus is a common pathogen causing infections in humans with various degrees of severity, with pneumonia being one of the most severe infections. In as much as staphylococcal pneumonia is a disease driven in large part by alpha-hemolysin (Hla) and Panton-Valentine leukocidin (PVL), we evaluated whether active immunization with attenuated forms of Hla (HlaH35L/H48L) alone, PVL components (LukS-PVT28F/K97A/S209A and LukF-PVK102A) alone, or combination of all three toxoids could prevent lethal challenge in a rabbit model of necrotizing pneumonia caused by the USA300 community-associated methicillin-resistant S. aureus. Rabbits vaccinated with Hla toxoid alone or PVL components alone were only partially protected against lethal pneumonia, whereas those vaccinated with all three toxoids had 100% protection against lethality. Vaccine-mediated protection correlated with induction of polyclonal antibody response that neutralized not only alpha-hemolysin and PVL, but also other related toxins, produced by USA300 and other epidemic MRSA clones.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31505732

RESUMO

OBJECTIVE: Our aim was to assess the changes in induced abortion in different migrant groups in China between 2007 and 2014 and the contraceptive methods used prior to induced abortion. METHODS: The studies of two population-based cross sections were conducted in urban China, involving 9146 sexually active migrant women. Within the selected sociodemographic subgroups, the changes in the percentage of women who had induced abortions, the proportion of pregnancies ending in induced abortions, the causes of induced abortions, and the methods of contraception were identified. A chi-squared test was used to calculate the differences in induced abortion in the subgroups. RESULTS: Between 2007 and 2014, in the study groups from the major cities of China, the percentage of sexually active migrant women who had induced abortions increased 10.1%, from 21.8% to 24.0%. The proportion of pregnancies ending in induced abortions increased 23.7%, from 21.5% to 26.6%. Both of the aforementioned statistics increased significantly within most of the selected sociodemographic subgroups, especially in the 18-19 and 45-49 age groups. Over 50% of pregnancies were aborted in the cohabiting group, although this figure declined by 12.3% over the course of the seven-year study period. Contraceptive failure was the primary cause of induced abortion, although its contribution to induced abortion declined from 51.3% to 42.4%. The proportion of women not using contraception prior to induced abortion increased from 30.9% to 41.2%. CONCLUSION: The prevalence of induced abortion is high and continues to increase among sexually active migrant women in China. An increasing trend is forecasted over the next few decades. Special attention should be paid to the younger cohort of migrant women, especially 18-19-year-olds, and unmarried cohabitants, who are increasingly seeking induced abortions.

10.
Mater Sci Eng C Mater Biol Appl ; 104: 110002, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31499949

RESUMO

Although PVA-chitosan composite hydrogel has excellent biocompatibility and antibacterial ability, its poor mechanical strength limits its application for wound dressings. Furthermore, PVA-chitosan composite hydrogel cannot satisfy the requirements of wound dressing as an environmental conditioner to accelerate wound healing. In this work, a novel lignin-chitosan-PVA composite hydrogel was prepared as wound dressing. The introduction of lignin effectively improved the mechanical strength (tensile stress is up to 46.87 MPa), protein adsorption capacity, and wound environmental regulation ability of the hydrogel. In a murine wound model, the lignin-chitosan-PVA composite hydrogel significantly accelerated wound healing. The developed hydrogel provides new opportunities for highly efficient skin wound care and management.

11.
Int J Mol Sci ; 20(18)2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31500178

RESUMO

All living things have pyrophosphatases that hydrolyze pyrophosphate and release energy. This energetically favorable reaction drives many energetically unfavorable reactions. An accepted catalytic model of pyrophosphatase shows that a water molecule activated by two divalent cations (M1 and M2) within the catalytic center can attack pyrophosphate in an SN2 mechanism and thus hydrolyze the molecule. However, our co-crystal structure of Acinetobacter baumannii pyrophosphatase with pyrophosphate shows that a water molecule from the solvent may, in fact, be the actual catalytic water. In the co-crystal structure of the wild-type pyrophosphatase with pyrophosphate, the electron density of the catalytic centers of each monomer are different from one another. This indicates that pyrophosphates in the catalytic center are dynamic. Our mass spectroscopy results have identified a highly conserved lysine residue (Lys30) in the catalytic center that is phosphorylated, indicating that the enzyme could form a phosphoryl enzyme intermediate during hydrolysis. Mutation of Lys30 to Arg abolished the activity of the enzyme. In the structure of the apo wild type enzyme, we observed that a Na+ ion is coordinated by residues within a loop proximal to the catalytic center. Therefore, we mutated three key residues within the loop (K143R, P147G, and K149R) and determined Na+ and K+-induced inhibition on their activities. Compared to the wild type enzyme, P147G is most sensitive to these cations, whereas K143R was inactive and K149R showed no change in activity. These data indicate that monovalent cations could play a role in down-regulating pyrophosphatase activity in vivo. Overall, our results reveal new aspects of pyrophosphatase catalysis and could assist in the design of specific inhibitors of Acinetobacter baumannii growth.

12.
Eur J Clin Nutr ; 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477797

RESUMO

BACKGROUND/OBJECTIVES: Many studies have suggested that probiotics may be applied as a therapeutic agent for non-alcoholic fatty liver disease (NAFLD). However, the effects of frequent yogurt consumption (as a natural probiotic source) on NAFLD remain poorly understood. This study was to examine the association of habitual yogurt consumption with newly diagnosed NAFLD in the general adult population. SUBJECT/METHODS: Overall, 24,389 adults were included in this cross-sectional study. Yogurt consumption was estimated by using a validated self-administered food frequency questionnaire. NAFLD was diagnosed by abdominal ultrasonography. We used logistic regression models to assess the association between yogurt consumption categories and newly diagnosed NAFLD. RESULTS: The multivariable odds ratios with 95% confidence interval of newly diagnosed NAFLD were 1.00 (0.88, 1.14) for 1 time/week, 0.91 (0.81, 1.02) for 2-3 times/week, and 0.86 (0.76, 0.98) for ≥4 times/week (P for trend = 0.01), compared with those who consumed <1 time/week yogurt. The inverse association was observed in a sensitivity analysis. CONCLUSION: Higher yogurt consumption was inversely associated with the prevalence of newly diagnosed NAFLD. These results are needed to be confirmed in randomized controlled trials or prospective studies.

13.
Cell Cycle ; : 1-16, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31478449

RESUMO

Aneuploidy caused by abnormal chromosome segregation during early embryo development leads to embryonic death or congenital malformation. Centromere protein F (CENPF) is a member of centromere protein family that regulates chromosome segregation during mitosis. However, its necessity in early embryo development has not been fully investigated. In this study, expression and function of CENPF was investigated in mouse early embryogenesis. Detection of CENPF expression and localization revealed a cytoplasm, spindle and nuclear membrane related dynamic pattern throughout mitotic progression. Farnesyltransferase inhibitor (FTI) was employed to inhibit CENPF farnesylation in zygotes. The results showed that CENPF degradation was inhibited and its specific localization on nuclear membranes in morula and blastocyst vanished after FTI treatment. Also, CAAX motif mutation leads to failure of CENPF-C630 localization in morula and blastocyst. These results indicate that farnesylation plays a key role during CENPF degradation and localization in early embryos. To further assess CENPF function in parthenogenetic or fertilized embryos development, morpholino (MO) and Trim-Away were used to disturb CENPF function. CENPF knockdown in Metaphase II (MII) oocytes, zygotes or embryos with MO approach resulted in failure to develop into morulae and blastocysts, revealing its indispensable role in both parthenogenetic and fertilized embryos. Disturbing of CENPF with Trim-Away approach in zygotes resulted in impaired development of 2-cell and 4-cell, but did not affect the morula and blastocyst formation because of the recovered expression of CENPF. Taken together, our data suggest CENPF plays an important role during early embryonic development in mice. Abbreviation: CENPF: centromere protein F; MO: morpholino; FTI: Farnesyltransferase inhibitor; CENPE: centromere protein E; IVF: in vitro fertilization; MII: metaphase II; SAC: spindle assembly checkpoint; Mad1: mitotic arrest deficient 1; BUB1: budding uninhibited by benzimidazole 1; BUBR1: BUB1 mitotic checkpoint serine/threonine kinase B; Cdc20: cell division cycle 20.

14.
J Cell Mol Med ; 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31449345

RESUMO

Quaking homolog (QKI) is a member of the RNA-binding signal transduction and activator of proteins family. Previous studies showed that QKI possesses the tumour suppressor activity in human cancers by interacting with the 3'-untraslated region (3'-UTR) of various gene transcripts via the STAR domain. This study first assessed the association of QKI-6 expression with clinicopathological and survival data from bladder cancer patients and then investigated the underlying molecular mechanisms. Bladder cancer tissues (n = 223) were subjected to immunohistochemistry, and tumour cell lines and nude mice were used for different in vitro and in vivo assays following QKI-6 overexpression or knockdown. QKI-6 down-regulation was associated with advanced tumour TNM stages and poor patient overall survival. QKI-6 overexpression inhibited bladder cancer cell growth and invasion capacity, but induced tumour cell apoptosis and cell cycle arrest. Furthermore, ectopic expression of QKI-6 reduced tumour xenograft growth and expression of proliferation markers, Ki67 and PCNA. However, knockdown of QKI-6 expression had opposite effects in vitro and in vivo. QKI-6 inhibited expression of E2 transcription factor 3 (E2F3) by directly binding to the E2F3 3'-UTR, whereas E2F3 induced QKI-6 transcription by binding to the QKI-6 promoter in negative feedback mechanism. QKI-6 expression also suppressed activity and expression of nuclear factor-κB (NF-κB) signalling proteins in vitro, implying a novel multilevel regulatory network downstream of QKI-6. In conclusion, QKI-6 down-regulation contributes to bladder cancer development and progression.

15.
Chemphyschem ; 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31418994

RESUMO

Our recent work (J. Phys. Chem. Lett. 2019, 10, 2378) reported the discovery of the abnormal pnictogen dual aromaticity (π and σ) in cyclo-N5 - , which makes the anion unstable in nature but confers enhanced stability in sufficiently acid solution. Herein, we present systematic quantum calculations on the structures, energetics and dynamics of the pentazolate salt and metal pentazolate hydrates, focusing on the mechanism and functionality of the pnictogen dual aromaticity in these crystals, which are verified by experiments. We find that owning a net charge of -e is crucial to the formation of the dual aromaticity and the stabilization of the cyclo-N5 - . The competition between the dual aromaticity and the proton affinity drives the cyclo-N5 - to be unreactive to acid and remain unprotonated in these crystals. We decompose the crystal packing effect into pure mechanical compression and interspecies nonbonding interactions, and figure out that the type and number of the adjacent counterions of the cyclo-N5 - anion, instead of the compression effect, accounts for the protonation state reversion in the vacuum and in the crystal. The current work supports our original conclusion (Science 2018, 359, eaas8953) and is expected to provide compelling evidence against the current debate on the cyclo-N5 - stability (Science 2018, 359, eaao3672; J. Phys. Chem. Lett. 2018, 9, 7137; J. Am. Chem. Soc. 2019, 141, 2984).

16.
Biomolecules ; 9(9)2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31461907

RESUMO

MicroRNAs (miRNAs), the post-transcriptional gene regulators, are known to play an important role in plant development. The identification of differentially expressed miRNAs could better help us understand the post-transcriptional regulation that occurs during maize internode elongation. Accordingly, we compared the expression of MIRNAs between fixed internode and elongation internode samples and classified six differentially expressed MIRNAs as internode elongation-responsive miRNAs including zma-MIR160c, zma-MIR164b, zma-MIR164c, zma-MIR168a, zma-MIR396f, and zma-MIR398b, which target mRNAs supported by transcriptome sequencing. Functional enrichment analysis for predictive target genes showed that these miRNAs were involved in the development of internode elongation by regulating the genes respond to hormone signaling. To further reveal how miRNA affects internode elongation by affecting target genes, the miRNA-mRNA-PPI (protein and protein interaction) network was constructed to summarize the interaction of miRNAs and these target genes. Our results indicate that miRNAs regulate internode elongation in maize by targeting genes related to cell expansion, cell wall synthesis, transcription, and regulatory factors.

17.
Chem Commun (Camb) ; 55(69): 10320, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31407746

RESUMO

Correction for 'Click and photo-release dual-functional nucleic acid nanostructures' by Vibhav A. Valsangkar et al., Chem. Commun., 2019, DOI: 10.1039/c9cc03806j.

18.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(7): 878-883, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31441414

RESUMO

OBJECTIVE: To compare the influences of extracorporeal cardiopulmonary resuscitation (ECPR) and conventional or mechanical cardiopulmonary resuscitation (CCPR/MCPR) on survival rate and neurological outcome for adult patients with out-of-hospital cardiac arrest (OHCA), and to assess the effect of ECPR. METHODS: Databases such as Medline, Embase, ScienceDirect, HighWire, Cochrane Library, Wanfang Database and China National Knowledge Infrastructure (CNKI) were searched from January 2000 to October 2018 to retrieve clinical trials on comparison of the effect of ECPR and CCPR/MCPR on survival rate and neurological outcome of adult patients with OHCA. Thereafter, the studies retrieved were based on predefined inclusion and exclusion criteria. Data were extracted and the quality of the included studies was evaluated by two researchers. A meta-analysis was performed by using RevMan 5.3 software. Sensitivity analysis was used to evaluate the stability of the results, and funnel plot was used to evaluate publication bias. RESULTS: A total of 12 studies and 2 519 patients were enrolled, including 615 patients receiving ECPR and 1 904 patients receiving CCPR/MCPR. Meta-analysis showed that compared with CCPR/MCPR, ECPR could not improve the short-term (at hospital discharge or within 1 month) survival rate in patients with OHCA [odds ratio (OR) = 2.26, 95% confidence interval (95%CI) = 0.95-5.41, P = 0.07], but could increase long-term (at more than 3 months) survival rate (OR = 3.56, 95%CI = 1.65-7.71, P = 0.001), rate of good neurological outcome at hospital discharge [Glasgow-Pittsburgh cerebral performance categories (CPC) 1-2 was defined as good neurological function; OR = 3.39, 95%CI = 1.73-6.62, P = 0.000 4], and rate of good long-term neurological outcome (OR = 3.45, 95%CI = 2.24-5.32, P < 0.000 01). Sensitivity analysis showed that the overall results did not change significantly, whether using fixed-effect model and random-effect model to analyze the differences of each effect index, or excluding one study with fewer than 50 subjects for data analysis, indicating that the results were more stable. The funnel plot suggested that there was no publication bias in the studies. But due to the small number of studies, the publication bias could not be excluded. CONCLUSIONS: ECPR could not improve the short-term survival rate at hospital discharge or within 1 month in patients with OHCA, but could increase long-term survival rate at more than 3 months, good neurological outcome at hospital discharge and long-term neurological outcome.

19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1046-1052, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418355

RESUMO

OBJECTIVE: To investigate the relationship between the expression of lysosomal membrane proteins LAMP1, TPC1 and TPC2 in acute myeloid leukemia (AML) cells and clinical indications of AML and to explore the possible role in the genesis and development of AML and clinical significance. METHODS: Real-time quantitative PCR was used to detect the mRNA expression of LAMP1, TPC1 and TPC2 in AML cell lines (HL-60, NB4) and 57 patients with acute myeloid leukemia (including 44 initially treated patients and 13 relapsed and refractory patients). The relationship of mRNA expression levels with clinical indicators and post-chemotherapy remission was analyzed. RESULTS: Compared with CD34+ hematopoietic stem cells (HSC), the expression levels of LAMP1 and TPC1 in AML cell lines HL-60 and NB4 significantly increased, while the expression level of TPC2 was not significantly different. The expression levels of LAMP1, TPC1 and TPC2 in bone marrow mononuclear cells (BMMNC) of AML patients were higher than those in normal human BMMNC (P<0.05), and the expression levels of LAMP1, TPC1 and TPC2 in CD34+ primary AML cells(CD34+ primary cells in the patient's bone marrow >90%) were also high. There was no significant difference in the expression of LAMP1, TPC1 and TPC2 between CD34+HSC of patients with AML and relapsed/refractory patients (P>0.05). No correlation was found between age, sex and genotype and expression of membrane proteins (P>0.05). The expression levels of LAMP1 and TPC1 positively correlated with the number of white blood cells in peripheral blood of patients (P<0.01). LAMP1 and TPC2 were found to be associated with remission after a course of chemotherapy in newly diagnosed patients. Initially treated patients with high expression of LAMP1 in the bone marrow not easily relieved after one course of chemotherapy. Patients with high expression of TPC2 in the bone marrow more likely to be relieved after one course of chemotherapy. CONCLUSION: The mRNA of the three membrane proteins are highly expressed in AML patients, and LAMP1 and TPC1 are risk factors for AML disease progression. High expression of TPC2 is beneficial for chemotherapy of patients with newly diagnosed AML.


Assuntos
Leucemia Mieloide Aguda , Medula Óssea , Células da Medula Óssea , Células-Tronco Hematopoéticas , Humanos , Glicoproteínas de Membrana Associadas ao Lisossomo
20.
Diabetes Obes Metab ; 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31364797

RESUMO

AIMS: To evaluate a novel tetrahydroisoquinoline derivative YR4-42 as a selective peroxisome proliferator-activated receptor γ (PPARγ) modulator (SPPARM) and explore its anti-diabetic effects in vitro and in vivo. MATERIALS AND METHODS: Using two standard full PPARγ agonists rosiglitazone and pioglitazone as controls, the PPARγ binding affinity and transactivation action of YR4-42 were evaluated using biochemical and cell-based reporter gene assays. The capacity of YR4-42 to recruit coactivators of PPARγ was also assessed. The effects of YR4-42 on adipogenesis and glucose consumption and PPARγ Ser273 phosphorylation were investigated in 3T3-L1 adipocytes. The effects of YR4-42 and pioglitazone, serving as positive control, on glucose and lipids metabolism were investigated in high-fat diet-induced obese (DIO) C57BL/6J mice. The expression of PPARγ target genes involved in glucose and lipid metabolism was also assessed in vitro and in vivo. RESULTS: In vitro biochemical and cell-based functional assays showed that YR4-42 has much weaker binding affinity, transactivation, and recruitment to PPARγ of the coactivators thyroid hormone receptor-associated protein complex 220 kDa component (TRAP220) and PPARγ coactivator 1-α (PGC1α) compared to full agonists. In 3 T3-L1 adipocytes, YR4-42 significantly improved glucose consumption without a lipogenesis effect, while blocking tumour necrosis factor α-mediated phosphorylation of PPARγ at Ser273, thereby upregulating the expression of the PPARγ Ser273 phosphorylation-dependent genes. Furthermore, in DIO mice, oral administration of YR4-42 ameliorated the hyperglycaemia, with a similar insulin sensitization effect to that of pioglitazone. Importantly, YR4-42 also improved hyperlipidaemia-associated hepatic steatosis without weight gain, which avoids a major side effect of pioglitazone. Thus, YR4-42 appeared to selectively modulate PPARγ responses. This finding was supported by the gene expression analysis, which showed that YR4-42 selectively targets PPARγ-regulated genes mapped to glucose and lipid metabolism in DIO mice. CONCLUSIONS: We conclude that YR4-42 is a novel anti-diabetic drug candidate with significant advantages compared to standard PPARγ agonists. YR4-42 should be further investigated in preclinical and clinical studies.

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