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1.
Exp Physiol ; 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31475749

RESUMO

NEW FINDINGS: What is the central question of this study? We investigate whether NADPH oxidase activation mediates cardiac sympathetic nerve denervation and dysfunction in heart failure. What is the main findings and its importance? Cardiac sympathetic nerve terminal density and function were reduced in heart failure after myocardial infarction in rabbits. NADPH oxidase inhibitor apocynin prevents the reduction in cardiac sympathetic nerve terminal density and function in heart failure. These findings suggest that NADPH oxidase activation mediates cardiac sympathetic nerve terminal abnormalities in heart failure. NADPH oxidase may be a potential therapeutic target for cardiac sympathetic denervation and dysfunction in heart failure. ABSTRACT: Congestive heart failure (CHF) is characterized by cardiac sympathetic nerve terminal abnormalities, as evidenced by the decreases of norepinephrine transporter (NET) density and cardiac catecholaminergic and tyrosine hydroxylase (TH) profiles. These alterations are associated with increased reactive oxygen species (ROS). NADPH oxidase is a major source of ROS in CHF. In this study, we tested the hypothesis that NADPH oxidase activation mediates cardiac sympathetic nerve terminal abnormalities in CHF. CHF was produced by myocardial infarction (MI) in rabbits. Rabbits with MI or sham operation were randomized to orally receive an NADPH oxidase inhibitor apocynin (6 mg k-1 g/day) or placebo for 30 days. MI rabbits exhibited left ventricular (LV) dilation and systolic dysfunction, and the increases in NADPH oxidase activity and 4-hydroxynonenal expression in the remote non-infarcted myocardium, all of which were prevented by the treatment of apocynin. Cardiac catecholaminergic histofluorescence profiles and immunostained TH and PGP9.5 expression were decreased, and the decreases were ameliorated by the apocynin treatment. NET, TH and PGP9.5 protein and mRNA expression were reduced and the reduction was mitigated by the apocynin treatment. The effects of apocynin were confirmed by utilizing the NADPH oxidase inhibitor diphenyleneiodonium in a separate experiment. In conclusion, the NADPH oxidase inhibitor apocynin attenuated increased myocardial oxidative stress and decreased cardiac sympathetic nerve terminals in CHF after MI in rabbits. These findings suggest that the activation of NADPH oxidase mediates cardiac sympathetic nerve terminal abnormalities in CHF, and the inhibition of NADPH oxidase may be beneficial for the treatment of heart failure.

2.
J Psychopharmacol ; : 269881119872193, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31487208

RESUMO

PURPOSE: This study aimed to investigate the efficacy and tolerability of aripiprazole, olanzapine and risperidone in first-episode schizophrenia (FES). METHODS: The eight-week, open, randomised study was conducted in six Chinese medical centres. Altogether, 498 FES subjects were randomised to aripiprazole (n = 165), olanzapine (n = 168) or risperidone (n = 165). Efficacy was measured with the Positive and Negative Syndrome Scale (PANSS), tolerability with the Udvalg for Kliniske Undersogelser Side Effect Rating Scale (UKU) and functioning with the Personal and Social Performance Scale (PSP). RESULTS: All three antipsychotics significantly improved the baseline to end-point PANSS total and each of the sub-scale scores (p < 0.001). Risperidone was superior to olanzapine and aripiprazole regarding PANSS total end-point scores (p < 0.05). Cumulative response (PANSS total score reduction ⩾30%) was similar between risperidone, olanzapine and aripiprazole (74.8%, 73.5% and 70.1%; p = 0.707), but risperidone was superior to aripiprazole regarding PANSS total score reduction ⩾50% (37.8% vs. 26.6%; p < 0.05). Olanzapine was associated with the largest weight gain at week 4 and 8 (p < 0.01), weight gain ⩾7% (olanzapine = 49.0% vs. risperidone = 32.5% vs. aripiprazole = 17.0%; p < 0.01), more psychic side effects at week 8 (p < 0.01 each) and more 'other' side effects at week 4 (p < 0.001) and week 8 (p < 0.05) but fewer neurological side effects at week 4 (p < 0.05) and week 8 (p < 0.01). PSP improved more with risperidone than with aripiprazole at week 4 and 8 (p < 0.05). CONCLUSIONS: For FES, risperidone might be a better choice than aripiprazole due to improved efficacy and functional improvement, without inferior tolerability. Aripiprazole is a better choice to avoid relevant short-term weight gain. Olanzapine could be chosen to avoid neurological adverse effects.

3.
iScience ; 19: 676-690, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31472342

RESUMO

The metabolic improvement effect of blueberries has long been recognized, although its precise mechanism(s) remains obscure. Here, we show that phenolic blueberry extract (BE) treatment improved diet- and genetically induced metabolic syndromes, which were linked to increased energy expenditure in brown adipose tissue (BAT) and improved lipid metabolism in the liver via pathways involving the bile acid (BA) receptors TGR5 and FXR. These observations were strongly correlated with the regulation of BAs (e.g., a decrease in the FXR inhibitors TαMCA and TßMCA) and the gut microbiota (GM) (e.g., an expansion of Bifidobacteria and Lactobacillus), because antibiotic treatment completely blunted the regulation of the GM and BAs and the metabolic effects of BE. We also observed similar results in db/db mice. Furthermore, treating mouse primary cells derived from the liver and BAT with the combinations of BAs mimicking the in vivo alterations upon BE treatment mirrored the in vivo observations in mice.

4.
Cancer Res ; 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409638

RESUMO

Heat shock transcription factor 1 (HSF1) is the master regulator of the proteotoxic stress response, which plays a key role in breast cancer tumorigenesis. However, the mechanisms underlying regulation of HSF1 protein stability are still unclear. Here, we showed that HSF1 protein stability is regulated by PIM2-mediated phosphorylation of HSF1 at Thr120, which disrupts the binding of HSF1 to the E3 ubiquitin ligase FBXW7. In addition, HSF1 Thr120 phosphorylation promoted proteostasis and carboplatin-induced autophagy. Interestingly, HSF1 Thr120 phosphorylation induced HSF1 binding to the PD-L1 promoter, and enhanced PD-L1 expression. Furthermore, HSF1 Thr120 phosphorylation promoted breast cancer tumorigenesis in vitro and in vivo. PIM2, pThr120-HSF1 and PD-L1 expression positively correlated with each other in breast cancer tissues. Collectively, these findings identify PIM2-mediated HSF1 phosphorylation at Thr120 as an essential mechanism that regulates breast tumor growth, and potential therapeutic target for breast cancer.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31392383

RESUMO

Crocin is isolated from saffron and has multiple activities. There are many reports on its beneficial effects for cardiovascular disease, but crocin's effects on anti-myocardial fibrosis have not yet been reported. This study investigated crocin's effects and potential mechanisms on isoproterenol (ISO)-induced myocardial fibrosis (MF) in mice. Mice were infused intraperitoneally with crocin with concurrent ISO subcutaneous injections over 2 weeks. Electrocardiography, cardiac weight index (CWI), hydroxyproline content, and heart morphology changes were observed. Administration of crocin markedly decreased heart rate, J-point elevation, QRS interval, CWI, and hydroxyproline content in the myocardial tissues, and improved heart pathologic morphology. Versus the control group, the ISO group showed an increase in lactate dehydrogenase and creatine kinase activities and malondialdehyde content. Meanwhile, superoxide dismutase, catalase, and glutathione contents decreased in the ISO group; crocin caused a significant reduction in oxidative stress levels in ISO-induced MF. ISO led to a significant increase in interleukin-1 and -6 and tumor necrosis factor-α in addition to nuclear factor kappa B (NF-κB) (p65) and toll-like receptor (TLR) 4 expressions. Crocin treatment suppressed these inflammatory cytokine expressions. Moreover, crocin treatment caused a significant decrease in connective tissue growth factor and transforming growth factor-ß1 mRNA levels in addition to a decrease in B cell lymphoma-2, Bcl-2-associated X protein, caspase-3, and cleaved caspase-3 expressions. Crocin has a protective effect on ISO-induced MF, which may be associated with the TLR4/NF-κB (p65) signal transduction pathway.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31402550

RESUMO

The tumor complexity makes the development of high sensitive tumor imaging probes facing arduous tasks. Here, we construct a fibroblast activation protein-α (FAP-α) responsive peptide-based near infrared probe, which specifically in situ forms nanofibers on the surface of cancer associated fibroblasts (CAFs). The assembly/aggregation induced retention (AIR) effect endows the probe enhanced accumulation and retention around the tumor, resulting in 5.5-fold signal enhancement in tumor compared to that of the non-aggregatable control molecule post 24 h administration through ex vivo imaging. This probe provides a prolonged detectable windows over 48 h for tumor diagnosis. Meanwhile, the selective assembly of the probe widen the difference of accumulation in tumor and in metabolic organ (e.g. liver and kidney) resulting over 4-fold and 5-fold higher signal intensity in tumor than that of liver and kidney, respectively. With enhanced tumor imaging capability, this probe can visualize small tumors around 2 mm in diameter. We believe that our imaging strategy may offer a powerful tumor bioimaging approach with high specificity and sensitivity.

7.
Schizophr Res ; 2019 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-31387828

RESUMO

The present study aimed to explore the relationship between autistic and schizotypal traits in the non-clinical population. We first conducted a meta-analysis to quantify the correlation between self-reported autistic traits and the three dimensions of schizotypal traits (positive, negative and disorganization). The strongest correlation was found between autistic traits and negative schizotypal traits (r = 0.536, 95% CI [0.481, 0.586]), followed by the disorganization (r = 0.355, 95% CI [0.304, 0.404]) and positive (r = 0.256, 95% CI [0.208, 0.302]) dimensions. To visualize the partial correlations between dimensional behavioural traits, we constructed a network model based on a large sample of college students (N = 2469). Negative schizotypal traits were strongly correlated with autistic social/communicative deficits, whereas positive schizotypal traits were inversely correlated with autistic-like traits, lending support to the psychosis-autism diametrical model. Disentangling the overlapping and diametrical structure of autism and schizophrenia may help to elucidate the aetiology of these two neurodevelopmental disorders.

8.
Dalton Trans ; 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31451814

RESUMO

This study reports, for the first time, the second-harmonic generation (SHG) property of Pb7F12Cl2 as a promising infrared nonlinear optical (NLO) material. Powder second-harmonic generation (SHG) indicates that the compound exhibits phase-matchable SHG properties, which are 1.6 times stronger than those of KH2PO4 (KDP). The infrared transmission range could reach 20 µm. The UV absorption indicated that the band gap was about 4.5 eV. A preliminary measurement of laser damage threshold (LDT) is about 80 MW cm-2, which is much higher than AgGaS2 (currently commercialized IR NLO material, 5.2 MW cm-2, measured in the same condition), indicating that Pb7F12Cl2 is a potential IR NLO material with high LDT. Theoretical calculations were also performed to elucidate its band structure, electronic configuration and second-order nonlinear coefficients. Particularly, the distinct role of different Pb atoms located in divergent coordinations has also been elaborated using orbital analysis.

9.
Nat Prod Res ; : 1-7, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307232

RESUMO

Cladosporine A (1), a new indole diterpenoid alkaloid, was isolated from the extract of a fungal strain Cladosporium sp. JNU17DTH12-9-01. Its structure was elucidated by extensive spectroscopic analysis, and the absolute configurations were determined by electronic circular dichroism (ECD) experiments. This is the first report of the presence of indole diterpenoid alkaloid in the genus Cladosporium. The antimicrobial activities against Staphylococcus aureus 209P, Escherichia coli ATCC0111, Aspergillus niger R330, and Candida albicans FIM709 were evaluated. Compound 1 showed MICs of 4 µg/mL and 16 µg/mL against S. aureus 209P and C. albicans FIM709, respectively.

10.
Development ; 146(13)2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31273086

RESUMO

Exploration and dissection of potential actions and effects of long noncoding RNA (lncRNA) in animals remain challenging. Here, using multiple knockout mouse models and single cell RNA sequencing, we demonstrate that the divergent lncRNA Hand2os1/Uph has a key complex modulatory effect on the expression of its neighboring gene HAND2 and subsequently on heart development and function. Short deletion of the Hand2os1 promoter in mouse diminishes Hand2os1 transcription to ∼8-32%, but fails to affect HAND2 expression and yields no discernable heart phenotypes. Interestingly, full-length deletion of Hand2os1 in mouse causes moderate yet prevalent upregulation of HAND2 in hundreds of cardiac cells, leading to profound biological consequences, including dysregulated cardiac gene programs, congenital heart defects and perinatal lethality. We propose that the Hand2os1 locus dampens HAND2 expression to restrain cardiomyocyte proliferation, thereby orchestrating a balanced development of cardiac cell lineages. This study highlights the regulatory complexity of the lncRNA Hand2os1 on HAND2 expression, emphasizing the need for complementary genetic and single cell approaches to delineate the function and primary molecular effects of an lncRNA in animals.

11.
Schizophr Bull ; 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31355879

RESUMO

A phenomenon in schizophrenia patients that deserves attention is the high comorbidity rate with obsessive-compulsive disorder (OCD). Little is known about the neurobiological basis of schizo-obsessive comorbidity (SOC). We aimed to investigate whether specific changes in white matter exist in patients with SOC and the relationship between such abnormalities and clinical parameters. Twenty-eight patients with SOC, 28 schizophrenia patients, 30 OCD patients, and 30 demographically matched healthy controls were recruited. Using Tract-based Spatial Statistics and Probabilistic Tractography, we examined the pattern of white matter abnormalities in these participants. We also used ANOVA and Support Vector Classification of various white matter indices and structural connection probability to further examine white matter changes among the 4 groups. We found that patients with SOC had decreased fractional anisotropy (FA) and increased radial diffusivity in the right sagittal stratum and the left crescent of the fornix/stria terminalis compared with healthy controls. We also found changed connection probability in the Default Mode Network, the Subcortical Network, the Attention Network, the Task Control Network, the Visual Network, the Somatosensory Network, and the cerebellum in the SOC group compared with the other 3 groups. The classification results further revealed that FA features could differentiate the SOC group from the other 3 groups with an accuracy of .78. These findings highlight the specific white matter abnormalities found in patients with SOC.

12.
J Pharm Biomed Anal ; 174: 683-695, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31288191

RESUMO

Sensitive and comprehensive measurement of systemic metabolites of tryptophan, phenylalanine and glutamate metabolism in biological samples is effective for understanding the pathogenesis of depression and other neurological diseases. Therefore, this study developed an underivatized liquid chromatography tandem mass spectrometry (LC-MS/MS) method for simultaneous monitoring the 3 components of glutamate metabolism in rat hippocampus and 11 components of tryptophan and phenylalanine metabolism in rat hippocampus, plasma and urine, and applied it to investigate their changes in rats induced by chronic unpredictable mild stress (CUMS). The investigated analytes are as follows: tryptophan, serotonin, 5-hydroxyindoleacetic acid, kynurenine, kynurenic acid, xanthurenic acid, 3-hydroxyanthranilic acid, quinolinic acid, phenylalanine, tyrosine, tyramine, glutamate, glutamine and gamma-aminobutyric acid. The method was verified to be sensitive and effective with satisfactory linearity, accuracies in the range of 78.2%-120.4%, and precisions less than 17.8% for all identified analytes. A series of significant changes in CUMS-induced rats can be detected: tryptophan, serotonin and tyrosine levels decreased and quinolinic acid increased in both hippocampus and plasma. In addition, the kynurenine/tryptophan ratios increased in hippocampus and plasma, the kynurenic acid/quinolinic acid ratios of plasma and urine were significantly reduced. These findings demonstrated that the CUMS procedure could lead to the central and peripheral imbalances of tryptophan and phenylalanine metabolism. In conclusion, a LC-MS/MS method for simultaneous measurement of several neurotransmitters in rat hippocampus, plasma and urine was developed and successfully applied to investigation of the central and peripheral changes in CUMS-induced rats. The method would be expected to provide applicability to the study of the mechanisms of depression and other related diseases associated with these neurotransmitters.

13.
Oncogene ; 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31358902

RESUMO

Endometrial cancer (EC) is one of the most common gynecologic malignancies. However, the molecular mechanisms underlying the development and progression of EC remain unclear. Here, we demonstrated that the protein proviral insertion in murine lymphomas 2 (PIM2) was necessary for maintaining EC tumorigenesis in vivo and in vitro, and could inhibit AMPKα1 kinase activity in EC cells. Specifically, we found that PIM2 bound to AMPKα1, and directly phosphorylated it on Thr467. Phosphorylation of AMPKα1 by PIM2 led to decreasing AMPKα1 kinase activity, which in turn promoted aerobic glycolysis and tumor growth. In addition, PIM2 expression positively correlated with AMPKα1 Thr467 phosphorylation in EC tissues. Further, treatment with a combination of the PIM2 inhibitor SMI-4a and the AMPKα1 activator AICAR could effectively inhibit tumor growth. Thus, our findings provide insight into the role of PIM2 and AMPKα1 in EC and suggest that combination targeting of these proteins may represent a new strategy for EC treatment.

14.
Nat Commun ; 10(1): 3394, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31358765

RESUMO

The proline-type organocatalysts has been efficiently employed to catalyze a wide range of asymmetric transformations; however, there are still many synthetically useful and challenging transformations that remain unachievable in an asymmetric fashion. Herein, a chiral bifunctional organocatalyst with a spirocyclic pyrrolidine backbone-derived containing fluoro-alkyl and aryl sulfonamide functionalities, are designed, prepared, and examined in the asymmetric Mannich/acylation/Wittig reaction sequence of 3,4-dihydro-ß-carboline with acetaldehyde, acyl halides, and Wittig reagents. As a result, the spirocyclic pyrrolidine trifluoromethanesulfonamide catalyst can facilitate this versatile sequence as demonstrated by 18 examples displaying excellent enantioselectivity (up to 94% ee), as well as moderate to good yields (up to 54% over 3 steps). As a practical application, the asymmetric total synthesis of naucleofficine I (1a) and II (1b) in ten steps have been accomplished.

15.
Nanoscale ; 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31287484

RESUMO

CO oxidation is an important reaction both experimentally and industrially, and its performance is usually dominated by the charge states of catalysts. For example, CO oxidation on the platinum (Pt) surface requires a properly charged state for the balance of adsorption and activation of CO and O2. Here, we present "Mott-Schottky modulated catalysis" on Pt nanoparticles (NPs) via an electron-donating carbon nitride (CN) support with a tunable Fermi level. We demonstrate that properly-charged Pt presents an excellent catalytic CO oxidation activity with an initial conversion temperature as low as 25 °C and total CO conversion below 85 °C. The tunable electronic structure of Pt NPs, which is regulated by the Fermi level of CN, is a key factor in dominating the catalytic performance. This "Mott-Schottky modulated catalysis" concept may be extended to maneuver the charge state on other metal catalysts for targeted catalytic reactions.

16.
Bull Environ Contam Toxicol ; 103(1): 56-63, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31256201

RESUMO

MicroRNAs (miRNAs) differentially expressed in plasma were identified using microRNA sequencing (miRNA-seq), and five miRNAs were selected for validation. Potential target genes of these five miRNAs were predicted using the miRWalk3.0 database, and the overlapping portions were analyzed using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Comparison of the cases and controls revealed 127 known differentially expressed miRNAs. A total of 44 and 83 miRNAs were upregulated and downregulated, respectively. Through target gene prediction of five miRNAs, we obtained 1360 target genes. GO enrichment analysis showed that the target genes of these dysregulated miRNAs were related with secretion, protein binding, and cell growth. The KEGG pathway analysis showed that pathways in cancer, calcium signaling, and rat sarcoma (Ras) signaling, etc. were likely regulated by these five miRNAs. These findings highlight the distinct expression patterns of miRNAs in coal-burning endemic fluorosis.


Assuntos
Carvão Mineral , Biologia Computacional , Sequenciamento de Nucleotídeos em Larga Escala , MicroRNAs , Regulação para Cima
17.
Luminescence ; 2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31245914

RESUMO

The reduction of nuclear fast red (NFR) stain by sodium tetrahydroboron was catalyzed in the presence of silver ions (Ag+ ). The fluorescence properties of reduced NFR differed from that of NFR. The product showed fluorescence emission at 480 nm with excitation at 369 nm. Furthermore, the fluorescence intensity of the mixture increased strongly in the presence of Ag+ and Britton-Robinson buffer at pH 4.78. There was a good linear relationship between increased fluorescence intensity (ΔI) and Ag+ concentration in the range 5.0 × 10-9 to 5.0 × 10-8  M. The correlation coefficient was 0.998, and the detection limit (3σ/k) was 1.5 × 10-9  M. The colour of the reaction system changed with variation in Ag+ concentration over a wide range. Based on the colour change, a visual semiquantitative detection method for recognition and sensing of Ag+ was developed for the range 1.0 × 10-8  to 5.0 × 10-4  M, with an indicator that was visible to the naked eye. Therefore, a sensitive, simple method for determination of Ag+ was developed. Optimum conditions for Ag+ detection, the effect of other ions and the analytical application of Ag+ detection of synthesized sample were investigated.

18.
Neuroscience ; 413: 206-218, 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31220544

RESUMO

Accumulating evidence indicates that phosphorylated serum- and glucocorticoid-regulated kinase 1 (SGK1) is associated with spinal nociceptive sensitization by modulating glutamatergic N-methyl-D-aspartate receptors (NMDARs). In this study, we determined whether spinal SGK1 signaling contributes to the development of morphine analgesic tolerance. Chronic morphine administration markedly induced phosphorylation of SGK1 in the spinal dorsal horn neurons. Intrathecal injection of SGK1 inhibitor GSK-650394 reduced the development of morphine tolerance with a significant leftward shift in morphine dose-effect curve. Furthermore, spinal inhibition of SGK1 suppressed morphine-induced phosphorylation of nuclear factor kappa B (NF-κB) p65 and upregulation of NMDAR NR1 and NR2B expression in the spinal dorsal horn. In contrast, intrathecal administration of NMDAR antagonist MK-801 had no effect on the phosphorylation of SGK1 in morphine-treated rats. In addition, morphine-induced upregulation of NR2B, but not NR1, was significantly abolished by intrathecal pretreatment with PDTC, a specific NF-κB activation inhibitor. Finally, spinal delivery of SGK1 small interfering RNA exhibited similar inhibitory effects on morphine-induced tolerance, phosphorylation of NF-κB p65, as well as upregulation of NR1 and NR2B expression. Our findings demonstrate that spinal SGK1 contributes to the development of morphine tolerance by enhancing NF-κB p65/NMDAR signaling. Interfering spinal SGK1 signaling pathway could be a potential strategy for prevention of morphine tolerance in chronic pain management.

19.
J Cell Biochem ; 120(10): 18370-18377, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31190333

RESUMO

BACKGROUND: Nicotine, an important component of tobacco, is a major risk factor of lung cancer, but the mechanism through which nicotine promotes lung cancer development remains unclear. METHODS: Eighty patients with lung cancer were enrolled in this study, 34 of whom did not smoke and the others did. The expression of miR-218 and CDK6 messenger RNA (mRNA) was measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR). A luciferase reporter system was used to identify the direct target of miR-218. The protein expression of CDK6 was analyzed by using Western blotting. Cell proliferation was analyzed using an approach of calculation of cell number under a microscope. RESULTS: Nicotine decreased miR-218 expression in non-small cell lung cancer (NSCLC) cells and promoted proliferation of NSCLC cells. Smoking patients with NSCLC had lower expression of miR-218 in tumor compared with NSCLC patients who did not smoke. We found that miR-218 directly targeted the CDK6 mRNA 3'untranslated region and inhibited its expression in NSCLC cells and also observed a negative correlation between the expression of miR-218 and CDK6 mRNA in lung cancer tissues. Furthermore, miR-218- or nicotine-induced proliferative effects of NSCLC cells were rescued by the recovery of the expression level of CDK6. CONCLUSION: Nicotine promotes proliferation of NSCLC cells through regulating the miR-218/CDK6 axis, which may be a potential therapeutic target for lung cancer.

20.
Dermatol Ther ; 32(4): e12992, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31172649

RESUMO

Vitiligo is a disease pathologically characterized by specific damage to melanocytes. The aim of this study was to explore the mechanism underlying CO2 fractional laser treatment of vitiligo by detecting the levels of Th1 cytokines (IL-2 and IFN-γ), Th2 cytokines (IL-4 and IL-10), and Th17 cytokines (IL-17 and IL-23) in peripheral blood. Twenty five vitiligo patients were enrolled in this study and were treated with a CO2 fractional laser four to eight times. The cytokines of 25 vitiligo patients and 20 healthy volunteers were measured by enzyme-linked immunosorbent assay. After CO2 fractional laser therapy, six cases were cured, and the apparent efficiency was 72.0% (18/25), while the efficiency was 92.0% (23/25). Before CO2 fractional laser therapy, IL-2 and IFN-γ levels in vitiligo patients were higher than those in the control group, but the difference was not statistically significant (p > .05). IL-4, IL-10, IL-17, and IL-23 levels were also higher in vitiligo patients than those in the control group (p < .05). After treatment, IL-2 and IFN-γ levels in vitiligo patients were lower than before treatment, but the difference was not statistically significant (p > .05), while IL-4, IL-10, IL-17, and IL-23 levels were significantly lower compared with before treatment (p < .05). The results show that CO2 fractional laser treatment has a good curative effect in the treatment of vitiligo.

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