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1.
Artigo em Inglês | MEDLINE | ID: mdl-31673961

RESUMO

PURPOSE: Acute ischemic stroke is one of the most causes of death all over the world. Onset to treatment time is critical in stroke diagnosis and treatment. Considering the time consumption and high price of MR imaging, CT perfusion (CTP) imaging is strongly recommended for acute stroke. However, too much CT radiation during CTP imaging may increase the risk of health problems. How to reduce CT radiation dose in CT perfusion imaging has drawn our great attention. METHODS: In this study, the original 30-pass CTP images are downsampled to 15 passes in time sequence, which equals to 50% radiation dose reduction. Then, a residual deep convolutional neural network (DCNN) model is proposed to restore the downsampled 15-pass CTP images to 30 passes to calculate the parameters such as cerebral blood flow, cerebral blood volume, mean transit time, time to peak for stroke diagnosis and treatment. The deep restoration CNN is implemented simply and effectively with 16 successive convolutional layers which form a wide enough receptive field for input image data. 18 patients' CTP images are employed as training set and the other six patients' CTP images are treated as test dataset in this study. RESULTS: Experiments demonstrate that our CNN can restore high-quality CTP images in terms of structural similarity index (SSIM) and peak signal-to-noise ratio (PSNR). The average SSIM and PSNR for test images are 0.981 and 56.25, and the SSIM and PSNR of regions of interest are 0.915 and 42.44, respectively, showing promising quantitative level. In addition, we compare the perfusion maps calculated from the restored images and from the original images, and the average perfusion results of them are extremely close. Areas of hypoperfusion of six test cases could be detected with comparable accuracy by radiologists. CONCLUSION: The trained model can restore the temporally downsampled 15-pass CTP to 30 passes very well. According to the contrast test, sufficient information cannot be restored with, e.g., simple interpolation method and deep convolutional generative adversarial network, but can be restored with the proposed CNN model. This method can be an optional way to reduce radiation dose during CTP imaging.

2.
Neurosci Lett ; : 134595, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31682872

RESUMO

The pathogenesis of cancer induced bone pain (CIBP) is extremely complex, and glutamate receptor dysfunction plays an important role in the formation of CIBP. Synapse-associated protein 102 (SAP102) anchors glutamate receptors in the postsynaptic membrane. However, its effect on hyperalgesia formation in CIBP has not been clarified. This study investigated the role of SAP102 in the formation of hyperalgesia in rats with CIBP SAP102 is present in spinal dorsal horn neurons, but not in astrocytes or microglia. NMDAR-NR2B is localized with neurons. In addition, SAP102 and NMDAR-NR2B expression levels in spinal dorsal horn tissues were detected by Western blot and co-immunoprecipitation. Intrathecal injection of lentiviral vector of RNAi to knockdown SAP102 expression in the spinal dorsal horn significantly attenuated abnormal mechanic pain when compared to non-coding lentiviral vector. These findings indicate that SAP102 can anchor NMDA receptors to affect hyperalgesia formation in bone cancer pain.

3.
J Diabetes Res ; 2019: 7304140, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31687408

RESUMO

Insulin antibody (IA) may potentially affect a patient's glycemic control due to its variability in both binding and/or releasing insulin. However, the association between IA titer and daily glycemic variability (GV) is still unknown. We thus performed this cross-sectional, retrospective case-control study to assess the relationship between IA titer and mean amplitude glycemic excursion (MAGE) in type 2 diabetes mellitus (T2DM) patients using a continuous glucose monitoring (CGM) system. We recruited 100 eligible patients (IA > 5%, IA positive) and divided them into two groups-a low (L) group and a high (H) group-based on their IA titer. The control (C) group consisted of 47 patients (IA ≤ 5%, IA negative) matched for age, BMI, gender, and glycosylated hemoglobin A1c (HbA1c). The CGM determined the GV of enrolled patients. The primary outcome was the relationship between the IA titer and the MAGE, and the secondary outcome was the differences of GV among the three groups. We found that patients in the H group had higher levels of blood glucose fluctuation parameters than those in the L and C groups. The Ln(IA) was positively correlated with Ln(MAGE) even after adjusting for age, gender, BMI, HbA1c, and fasting and postprandial C-peptide(r = 0.423, p < 0.001). Multiple linear stepwise regression analysis revealed that Ln(IA) was an independent factor of Ln(MAGE) (beta = 0.405, p < 0.001). In conclusion, the higher circulating IA titer was associated with increased MAGE in T2DM patients, indicating that those patients with elevated IA titer should receive GV assessment and individualized treatment.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31727522

RESUMO

In this work, we developed a simple, effective fluorescence method to detect Hg2+ by inhibiting core-satellite assemblies of gold nanorods (AuNRs) and gold nanospheres (AuNPs). The fluorescence of Rhodamine 6G (Rh6G), which was simply mixed with the nanoassemblies, was efficiently quenched by the inner filter effect (IFE). When the heterogenous core-satellite nanostructures were assembled, the corresponding local surface plasmon resonance (LSPR) absorption shifts and broadens which results in the increase of the spectral overlap between the emission peak and the absorption band and more efficient energy transfer from Rh6G to nanoparticles. Fluorescence quenching efficiency is related to the size and number density of satellite nanoparticles. It is interesting that the AuNR-AuNP assemblies with the moderate size and high density of AuNPs have the best fluorescence quenching efficiency. In the presence of Hg2+, p-aminothiophenol (p-ATP) breaks away from the surface of AuNRs and competitively bounds to Hg2+, resulting in a low yield of the AuNR-AuNP assemblies, which further leads to the decrease of fluorescence quenching efficiency. Under the optimum conditions, the limit of detection (LOD) for Hg2+ was 0.18 nM, with an excellent linear response from 0.6 to 800 nM. Interference experiment and real samples detection indicate that these nanosensors endowed with higher sensitivity and selectivity for the detection of Hg2+ in the real samples. Compared with the conventional Hg2+ detection techniques, this method based on Hg2+ induced inhibition of core-satellite AuNR-AuNP assemblies has better performance and is suitable for the detection of Hg2+.

5.
Cell Prolif ; : e12630, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31713929

RESUMO

OBJECTIVES: miR-92b has been reported to play critical roles in several carcinomas; however, our understanding of the mechanisms by which miR-92b stimulates gastric cancer (GC) is incomplete. The aim of this study was to investigate the clinical significance and functional relevance of miR-92b in GC. MATERIALS AND METHODS: Expression of miR-92b in GC and peritumoural tissues was determined using qRT-PCR, in situ hybridization and bioinformatics. CCK-8, colony formation and fluorescence-activated cell sorting assays were utilized to explore the effect of miR-92b on GC cells. A luciferase reporter assay and Western blotting were employed to verify miR-92b targeting of DAB2IP. Furthermore, Western blotting was used to evaluate the levels of DAB2IP and PI3K/Akt signalling pathway-related proteins. RESULTS: In this study, we found that miR-92b was upregulated in GC tissues compared with peritumoural tissues. Overexpression of miR-92b promoted cell proliferation, colony formation, and G0 /G1 transition and decreased apoptosis. Our results indicated that miR-92b repressed the expression of DAB2IP and that loss of DAB2IP activated the PI3K/AKT signalling pathway. Overexpression of DAB2IP rescued the effects of miR-92b in GC cells. Finally, our results demonstrated a significant correlation between miR-92b expression and DAB2IP expression in GC tissues. CONCLUSIONS: Our results suggest that miR-92b promotes GC cell proliferation by activating the DAB2IP-mediated PI3K/AKT signalling pathway. The miR-92b/DAB2IP/PI3K/AKT signalling axis may be a potential therapeutic target to prevent GC progression.

6.
Biomed Res Int ; 2019: 9731467, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31641670

RESUMO

Cardiotonic drugs mainly include digitalis, catecholamines, phosphodiesterase inhibitors, and calcium sensitizers, which have been successively discovered and applied in clinical practice. However, there are only a few new drugs available in this field, and the selection is very limited. Digitalis, catecholamines, and phosphodiesterase inhibitors increase myocardial contractility by increasing intracellular concentrations of cyclic adenosine monophosphate (cAMP) and Ca2+, and this increase in intracellular calcium ion concentration enhances myocardial oxygen consumption and causes arrhythmia. For these reasons, the research focus on positive inotropic agents has shifted from calcium mobilization to calcium sensitization. Intracellular calcium sensitizers are more effective and safer drugs because they do not increase the intracellular concentration of calcium ions. However, only three calcium sensitizers have been fully developed and used in the past three decades. One of these drugs, levosimendan, has multiple molecular targets and exerts its pharmacological effects by not only increasing myocardial contractility, but also enhancing respiratory muscle function and liver and kidney protection, and it is useful for patients with severe sepsis and septic shock. Recently, more than 60 randomized controlled clinical trials of levosimendan have been reported; however, these clinical trials have occasionally shown different findings. This article reviews the research progress of levosimendan in critical illnesses in recent years.

7.
Ann Rheum Dis ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31662318

RESUMO

OBJECTIVES: Diverse evidence including clinical, genetic and microbiome studies support a major role of the gut microbiome in the common immune-mediated arthropathy, ankylosing spondylitis (AS). We set out to (1) further define the key microbial characteristics driving disease, and (2) examine the effects of tumour necrosis factor-inhibitor (TNFi) therapy upon the microbiome. METHODS: The stools from a case-control cohort of 250 Han-Chinese subjects underwent shotgun metagenomic sequencing. All subjects were genotyped using the Illumina CoreExome SNP microarray. RESULTS: Previous reports of gut dysbiosis in AS were reconfirmed and several notable bacterial species and functional categories were differentially abundant. TNFi therapy was correlated with a restoration the perturbed microbiome observed in untreated AS cases to that of healthy controls, including several important bacterial species that have been previously associated with AS and other related diseases. Enrichment of bacterial peptides homologous to HLA-B27-presented epitopes was observed in the stools of patients with AS, suggesting that either HLA-B27 fails to clear these or that they are involved in driving HLA-B27-associated immune reactions. TNFi therapy largely restored the perturbed microbiome observed in untreated AS cases to that of healthy controls, including several important bacterial species that have been previously associated with AS and other related diseases. TNFi therapy of patients with AS was also associated with a reduction of potentially arthritogenic bacterial peptides, relative to untreated patients. CONCLUSION: These findings emphasise the key role that the gut microbiome plays in driving the pathogenesis of AS and highlight potential therapeutic and/or preventative targets.

8.
Neurocrit Care ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31576483

RESUMO

BACKGROUND AND OBJECTIVE: Attenuation of neuronal apoptosis helps maintain neurological function in patients after cardiac arrest. After ischemia-reperfusion, both cyclosporin A (CsA) and ischemic postconditioning independently protect mitochondria and thus reduce nerve injury. This study employed a rat model to evaluate the neuroprotective effect of combining ischemic postconditioning with CsA after cardiopulmonary resuscitation (CPR). METHODS: Rats were apportioned equally to model control, postconditioned, CsA-treated, or CsA + postconditioned groups. Asphyxial cardiac arrest was imposed using modified Utstein-style guidelines. In the appropriate groups, postconditioning was implemented by ischemia and reperfusion (clamping and loosening the left femoral artery); CsA treatment was delivered with a single intravenous dose. Neurological deficits were scored at different times after CPR. Histological evaluation and electron microscopy were used to evaluate tissue damage, and TUNEL and flow cytometry were used to measure the apoptotic rate of hippocampal neurons and size of the mitochondrial permeability transition pore (mPTP) opening. RESULTS: The apoptotic rate was significantly lower in the postconditioned and CsA-treated groups compared with the model control and lowest in the CsA + postconditioned group. By histological evaluation and electron microscopy, the least damage was observed in the CsA + postconditioned group. The neurological deficit score of the CsA + postconditioned group was significantly higher than that of the CsA-treated group, but the size of the mPTP openings of these two groups was comparable. CONCLUSION: Ischemic postconditioning combined with CsA exerted a better neuroprotective effect after CPR than did either postconditioning or CsA alone. Inhibiting the opening of the mPTP is not the only neuroprotective mechanism.

9.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 36(5): 879-884, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31631639

RESUMO

Radiotherapy is one of the main treatments for tumor with increasingly high request for technique precision and the equipment stability. Machine learning may bring radiotherapy simplicity, individualization and precision, and may improve the automatic level of planning and quality assurance. Based on the process of radiotherapy, this paper reviews the applications and researches on machine learning, with an emphasis on deep learning, and proposes the prospects in the following aspects: segmentation of normal tissue and tumor, planning, treatment delivery, quality assurance and prognosis prediction.


Assuntos
Aprendizado de Máquina , Neoplasias/radioterapia , Aprendizado Profundo , Humanos
10.
Eur J Med Res ; 24(1): 35, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31651357

RESUMO

BACKGROUND: Acute cerebrovascular disease (ACVD) could cause abnormal metabolism of thyroid hormones (TH), mostly represented as a euthyroid sick syndrome or low T3 syndrome. However, the changes in serum thyroid-stimulating hormone (TSH) are controversial. The aim of this study is to investigate the clinical significance of TSH alteration in patients with ACVD. METHOD: Patients with ACVD admitted in our hospitals between January 2013 and September 2017 were enrolled in this study (n = 245, including 176 cerebral infarctions and 69 cerebral hemorrhages). Their thyroid hormones were measured and compared with healthy individuals (n = 75). The correlation of TSH with severity and prognosis of ACVD were analyzed by receiver operating characteristic curve. RESULTS: Serum TSH in ACVD group was higher than the control group (1.64 ± 1.08 vs. 1.26 ± 0.36 µIU/mL, P < 0.05). The TSH levels in intermediate and severe patients with ACVD were higher than in mild patients (1.72 ± 1.18 vs. 2.71 ± 0.93 vs. 1.02 ± 0.47 µIU/mL, P < 0.05). Receiver Operating Characteristic curve (ROC) of TSH in determining the severity of patients were 0.863 (Area under the curve, AUC), 1.496 µIU/L (optimal threshold), 76.5% (sensitivity) and 87.3% (specificity). TSH levels in improved and unchanged groups were significantly higher than the primarily healing group (2.27 ± 1.11 vs. 2.88 ± 1.07 vs. 0.86 ± 0.46 µIU/mL, P < 0.05). ROC of TSH in determining the prognosis of patients was 0.910 (AUC), 1.681 mIU/L (optimal threshold), 79.8% (sensitivity) and 90.5% (specificity) correspondingly. CONCLUSION: Since elevated TSH in ACVD patients affects the outcome of thyroid function evaluation, it is preferable to re-check after the acute period. A correlation between a high TSH level and the severity and prognosis of ACVD was detected, but the mechanism of this correlation needs to be further studied.

11.
J Mol Biol ; 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31626810

RESUMO

The effects of RNA methylation on HIV-1 replication remain largely unknown. Recent studies have discovered new insights into the effect of 2'-O-methylation and methylcytidine marks on the HIV-1 RNA genome. As so far, HIV-1 benefits from diverse RNA methylations through distinct mechanisms. In this review, we summarize the recent advances in this emerging field and discuss the role of RNA methylation writers and readers in HIV-1 infection, which may help to find alternative strategies to control HIV-1 infection.

12.
Mol Psychiatry ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31570775

RESUMO

Increased expression of the 3.1 isoform of the KCNH2 potassium channel has been associated with cognitive dysfunction and with schizophrenia, yet little is known about the underlying pathophysiological mechanisms. Here, by using in vivo wireless local field potential recordings during working memory processing, in vitro brain slice whole-cell patching recordings and in vivo stereotaxic hippocampal injection of AAV-encoded expression, we identified specific and delayed disruption of hippocampal-mPFC synaptic transmission and functional connectivity associated with reductions of SERPING1, CFH, and CD74 in the KCNH2-3.1 overexpression transgenic mice. The differentially expressed genes in mice are enriched in neurons and microglia, and reduced expression of these genes dysregulates the complement cascade, which has been previously linked to synaptic plasticity. We find that knockdown of these genes in primary neuronal-microglial cocultures from KCNH2-3.1 mice impairs synapse formation, and replenishing reduced CFH gene expression rescues KCNH2-3.1-induced impaired synaptogenesis. Translating to humans, we find analogous dysfunctional interactions between hippocampus and prefrontal cortex in coupling of the fMRI blood oxygen level-dependent (BOLD) signal during working memory in healthy subjects carrying alleles associated with increased KCNH2-3.1 expression in brain. Our data uncover a previously unrecognized role of the truncated KCNH2-3.1 potassium channel in mediating complement activation, which may explain its association with altered hippocampal-prefrontal connectivity and synaptic function. These results provide a potential molecular link between increased KCNH2-3.1 expression, synapse alterations, and hippocampal-prefrontal circuit abnormalities implicated in schizophrenia.

13.
Genes Genomics ; 41(12): 1467-1474, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31576518

RESUMO

BACKGROUND: MiR-27 has been found to present an overt myocardial expression during cardiogenesis. However, whether miR-27 involves in myocarditis development and the possible molecular mechanism remain unknown. The purpose of this study was to investigate the biological characteristic of miR-27 in LPS-damaged H9c2 cells. METHODS: H9c2 cells were treated with lipopolysaccharide (LPS, 10 µg/ml) for 12 h to form cell injury. MiR-27 mimic and inhibitor were used to up-regulate or down-regulate miR-27 expression. MTT assay and flow cytometry analysis were conducted to test cell viability and apoptosis. The relative RNA expression level of miR-27 and intercellular adhesion molecule 1 (ICAM1) was determined by qRT-PCR. Luciferase reporter gene assay was utilized to confirm the interaction between miR-27 and ICAM1. Western blot was used to determine the protein expression levels. RESULTS: We observed that LPS treatment significantly decreased the level of miR-27 in H9c2 cells. Moreover, LPS exposure suppressed cell viability, promoted cell apoptosis and increased the relative expression of p-NF-κB p65/NF-κB p65 and p-IκBα/IκBα. Up-regulation of miR-27 increased cell proliferation and reduced cell apoptosis, while down-regulation of miR-27 suppressed cell growth and promoted cell apoptosis. ICAM1 was predicted and verified as a target of miR-27, and the expression of ICAM1 is negatively regulated by miR-27. The relative expression of p-NF-κB p65/NF-κB p65 and p-IκBα/IκBα was dramatically decreased by miR-27 mimic and increased by miR-27 inhibitor. CONCLUSION: Our study illustrated that up-regulation of miR-27 exhibits a protective effect on LPS-damaged H9c2 cells, which may be achieved by regulating ICAM1 and NF-κB signaling.

14.
J Mol Graph Model ; 94: 107455, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31586754

RESUMO

The human plasma cholesteryl ester transfer protein (CETP) collects triglycerides from very-/low-density lipoproteins (V/LDL) and exchanges them for cholesteryl esters from high-density lipoproteins (HDL), which has recognized as an important therapeutic target for atherosclerosis. The protein has a C-terminal amphipathic α-helix that serves as self-binding peptide to fulfill biological function by dynamically binding to/unbinding from its cognate site (termed self-binding site) in the same protein. Previously, we successfully derived and halogenated the helical peptide to competitively disrupt the self-binding behavior of CETP C-terminal tail. However, the halogenated peptides have only a limited affinity increase as compared to native helical peptide (∼3-fold), thus exhibiting only a moderate competitive potency. Here, instead of optimizing the direct intermolecular interaction of peptide with CETP self-binding site we attempt to further improve the peptide competitive potency by reducing its conformational flexibility with hydrocarbon-stapling technique. Computational analysis reveals that the helical peptide has large intrinsic disorder in unbound free state, which would incur a considerable entropy penalty upon rebinding to the self-binding site. All-hydrocarbon bridge is designed and optimized on native and halogenated peptides in terms of the helical pattern and binding mode of self-binding peptide. Dynamics simulation and circular dichroism indicate that the stapling can considerably reduce peptide disorder in free state. Energetics calculation and fluorescence assay conform that the binding affinity of stapled/halogenated peptides is improved substantially (by > 5-fold), thus exhibiting an effective competition potency with native peptide for the self-binding site. Structural examination suggests that the binding modes and nonbonded interactions of native and halogenated peptides are not influenced essentially due to the stapling.

15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1530-1539, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607308

RESUMO

OBJECTIVE: To retrospectively analyze the cases of multiple myeloma treated with chemotherapeatic regimens based on thalidomide, and to investigate the factors affecting MM patients treated using chemotherapeutic regimens with or without bortezomib. METHODS: The clinical, laboratorial and survival data of 200 patients with newly diagnosed MM from October 2007 to December 2015 were collected, and the correlation of clinical and laboratorial indicators with the clinical characteristics and prognosis of MM patients was analyzed by using χ2 test, COX regression analysis, Kaplan-Meier method and Log-rank test. RESULTS: Multivariable analysis showed that age (≥65 years old), ISS staging (Ⅲ), complex karyotypes and no-complete remission were the independent prognostic factors for OS in bortezomib-treated group, while the ß2-MG (≥8.95 mg/L), no-complete remission were the independent prognostic factros for OS in traditional therapy group. In addition, the MPI-1 myeloma prognostic index 1, consisted of age, complex karyotypes and complete remission in bortezomib-treated group, and MPI-2 consisted of ß2-MG (≥8.95 mg/L), complex karyotypes, complete remission in traditional therapy group were suitable for evaluating the pregnosis of MM patients treated with regimens contiaining bortezomib and traditional chemotherapentic regimans. CONCLUSION: The differences of prognostic factors exist in MM patients treated with different chemotherapeutic regimens, moreover, the patients with comples karyotypes and no-complete remisson have poor prognosis. The MPI as more simple and easy clinical parameter, may be come an useful and complemental method for evaluation of prognosis except ISS and R-ISS.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Bortezomib , Humanos , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
16.
Biomed Pharmacother ; 119: 109414, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31518875

RESUMO

Breast cancer ranks first among female malignancies worldwide, and estrogen receptor-positive (ER+) breast cancer is the leading cause of cancer death in women. Abnormal oncogenic signaling has important effects on the development of breast cancer, such as ERα/ ESR1 (estrogen receptor alpha), PTEN (gene of phosphate and tension homology deleted on chromsome ten), NFκB(nuclear factor κB), and tumor protein p53 (p53 / TP53). SHARPIN is a ubiquitin-related protein that has important regulatory functions in inflammation control, immune organ development, and cancer development. SHARPIN is highly expressed in many cancers, especially in breast cancer. It plays an important role in controlling important carcinogenic pathways in breast cancer, such as p53 and ERα. This review emphasizes the functional role of SHARPIN and the recent advances in the molecular mechanisms by which SHARPIN regulates breast cancer development through ubiquitination.

17.
J Nutr ; 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31504723

RESUMO

BACKGROUND: Selenium is prioritized to the brain mainly for selenoprotein expression. Selenoprotein T (SELENOT) protects dopaminergic, postmitotic neurons in a mouse model of Parkinson's disease (PD). OBJECTIVE: We hypothesized a proliferative role of SELENOT in neural cells. METHODS: To assess SELENOT status in PD, sedated male C57BL/6 mice at 10-12 wk of age were injected with 6-hydroxydopamine in neurons, and human peripheral blood mononuclear cells were isolated from 9 healthy subjects (56% men, 68-y-old) and 11 subjects with PD (64% men, 63-y-old). Dopaminergic neural progenitor-like SK-N-SH cells with transient SELENOT overexpression or knockdown were maintained in the presence or absence of the antioxidant N-acetyl-l-cysteine and the calcium channel blocker nimodipine. Cell cycle, proliferation, and signaling parameters were determined by immunoblotting, qPCR, and flow cytometry. RESULTS: SELENOT mRNA abundance was increased (P < 0.05) in SK-N-SH cells treated with 1-methyl-4-phenylpyridinium iodide (3.5-fold) and peripheral blood mononuclear cells from PD patients (1.6-fold). Likewise, SELENOT was expressed in tyrosine hydroxylase-positive dopaminergic neurons of 6-hydroxydopamine-injected mice. Knockdown of SELENOT in SK-N-SH cells suppressed (54%; P < 0.05) 5-ethynyl-2'-deoxyuridine incorporation but induced (17-47%; P < 0.05) annexin V-positive cells, CASPASE-3 cleavage, and G1/S cell cycle arrest. SELENOT knockdown and overexpression increased (88-120%; P < 0.05) and reduced (37-42%; P < 0.05) both forkhead box O3 and p27, but reduced (51%; P < 0.05) and increased (1.2-fold; P < 0.05) cyclin-dependent kinase 4 protein abundance, respectively. These protein changes were diminished by nimodipine or N-acetyl-l-cysteine treatment (24 h) at steady-state levels. While the N-acetyl-l-cysteine treatment did not influence the reduction in the amount of calcium (13%; P < 0.05) by SELENOT knockdown, the nimodipine treatment reversed the decreased amount of reactive oxygen species (33%; P < 0.05) by SELENOT overexpression. CONCLUSIONS: These cellular and mouse data link SELENOT to neural proliferation, expanding our understanding of selenium protection in PD.

19.
J Nutr Biochem ; 72: 108219, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31473507

RESUMO

Epithelial-mesenchymal transition (EMT) contributes to the initiation, invasion, metastasis and drug resistance of cancer. The function of extracellular signal-regulated kinase 5 (ERK5) in lung cancer progression remains elusive. In this study, we investigated the effect of sulforaphane (SFN) on lung cancer EMT and the role of ERK5 in its effect. Wound healing and Transwell assays were applied to examine the migratory and invasive capacity in vitro. Quantitative real-time polymerase chain reaction and immunoblotting analysis were performed to investigate the expression of mRNA and protein levels. Small-interfering RNA was used to silence ERK5. Xenograft model was used to confirm the effect of SFN in vivo. Enhanced EMT and decreased ERK5 activation were observed in lung cancer cells in comparison with normal human bronchial epithelial cells. SFN diminished the migratory and invasive capacity of lung cancer cells. Additionally, significantly increased expression of epithelial markers (E-cadherin and ZO-1), decreased expression of mesenchymal markers (N-cadherin and Snail1) and activation of ERK5 were observed after SFN treatment. The inhibitory effect of SFN on lung cancer cell EMT was attenuated by ERK5 silencing. SFN-induced EMT suppression and ERK5 activation were further confirmed in lung cancer xenograft mouse model. The present study illustrated for the first time that ERK5 activation mediates SFN suppression of lung cancer cell EMT. These findings could provide new insights into the function of ERK5 in EMT regulation and the potential therapeutic application of SFN in cancer intervention.

20.
Nanotechnology ; 31(1): 015402, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31514178

RESUMO

Germanium (Ge) has gained a great deal of attention as an anode material for sodium ion batteries (SIBs) and lithium ion batteries (LIBs) for its high theoretical capacity and ion diffusivity. Unfortunately, Ge particle pulverization triggered by huge volume expansion during the alloying and dealloying processes can cause rapid capacity fade. Herein we report a facile method for the preparation of ultrafine Ge nanoparticles embedded in hierarchical N-doped multichannel carbon fibers (denoted as Ge-NMCFs) by electrospinning. The hierarchical carbon matrix not only provides sufficient internal void space to accommodate the large volume expansion of Ge nanoparticles, but also provides numerous open channels for the easy access of electrolyte and Na/Li ions. As half-cell tests revealed, the composite provides discharge capacity of 303 mA h g-1 (1st cycle) and 160 mA h g-1 (700th cycle) for SIBs, 1146.7 mA h g-1 (1st cycle) and 600 mA h g-1 (500th cycle) for LIBs at a current density of 500 mA g-1 (all the presented capacity based on the total weight of Ge/C composites). Density functional theory calculation suggests that N-doped in carbon can enhance the Na/Li ion storage and improve the electrochemical performance. This demonstration is an important step towards the development of SIBs and LIBs with much higher specific energy capacity and longer cycle stability.

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