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1.
Artigo em Inglês | MEDLINE | ID: mdl-31472957

RESUMO

N6-methyladenosine (m6A) "readers" play an important role in mRNA functions and metabolism. YTHDC2, as one of the m6A readers, controls fertileness through decreasing associated mRNA abundance and enhancing the translation efficiency of related mRNA via binding the targeted m6A RNA. However, how YTH domain of YTHDC2 recognize m6A RNA is still unknown. In this study, we determined the crystal structure of human YTHDC2 YTH domain, which adopts similar architecture to other solved YTH domain structures. YTHDC2 contains a conserved m6A binding pocket, and similar RNA binding surface shared by YTHDC1.

2.
PLoS One ; 14(9): e0221551, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31490966

RESUMO

With the development and universal application of satellite technology, an important way to expand the function of satellites is setting up inter-satellite networks to make them work together. Traditional satellite networking methods generally adopt a fixed time slot allocation method, which is not suitable for small satellite groups with low latency and high throughput requirements. In order to solve this problem, it has been proposed to apply the traditional Wifi protocol in satellite networking. As there are differences between satellite networks and terrestrial networks, it's necessary to improve the traditional 802.11 protocol. The Media Access Control (MAC) protocol in 802.11 is improved in this paper, which mainly includes the adaptive algorithm of maximum contention window size and the growth algorithm of Contention Window (CW) size. The maximum contention window is adjusted according to the conflict state of the current network, which makes the network accommodate more satellite nodes. The CW growth algorithm improves the traditional Binary Exponential Back-off (BEB) algorithm, where the CW is designed according to the priority of the data frame or the network load. In this way, high-priority satellite accusation information will have higher reliability or tolerate greater network load.

3.
Gene ; 720: 144088, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31476404

RESUMO

BACKGROUND: Secretory leukocyte protease inhibitor (SPLI) was a secreted protein which belongs to a member of whey acidic protein four-disulfide core family. In breast cancer (BC) it may inhibit cell proliferation and promote cancer metastasis. In this study, a comprehensive bioinformatics analysis was performed to identify the expression and prognostic value of SLPI in breast cancer. METHODS: SLPI expression in breast cancer was analyzed in Oncomine online database, which was subsequently confirmed by quantitative PCR (qPCR) in 18 BC samples and western blotting in 26 BC samples. Breast cancer gene-expression miner v4.1 was used to access the expression level with clinicopathological parameters in breast cancer patients. The prognostic values of SLPI in breast cancer were evaluated using the PrognoScan database. RESULTS: Our results indicated that SLPI was downregulated in breast cancer than in normal tissues. SLPI expression was found to be negatively correlated with estrogen receptor (ER) and progesterone receptor (PR) status. SLPI expression level was decreased in negative basal-like status patients compared with positive basal-like status. Meanwhile, triple-negative breast cancer status positive correlated with SLPI. We confirmed a positive correlation between SLPI and interleukin 17 receptor B (IL17RB) express in breast cancer tissues via oncomine co-expression analysis. Ten proteins: Elastase, Granulin, Lipocalin, Defensin beta 103B, Defensin beta 103A, Tubulin, Heparin-binding EGF-like growth factor, Interleukin 6, Epidermal growth factor, Phospholipid scramblase 1 were determinate interactions with SLPI by STRING. CONCLUSION: SLPI could as a biomarker to predict the prognosis values of breast cancer. However, further comprehensive study and mining more evidence are needed to clarify our results.

4.
Eur J Med Chem ; 182: 111654, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31494474

RESUMO

A series of 1-benzyl-5-oxopyrrolidine-2-carboximidamide derivatives were designed and synthesized. Their protective activities against N-methyl-d-aspartic acid (NMDA)-induced cytotoxicity were investigated in vitro. All of the compounds exhibited neuroprotective activities, especially 12k, which showed higher potency than reference compound 1 (ifenprodil). Further investigation showed that 12k could attenuate Ca2+ influx and suppress the NR2B upregulation induced by NMDA. The docking results indicated that 12k could fit well into binding site of 1 in the NR2B-NMDA receptor. Additionally, 12k exhibited excellent metabolic stability. Furthermore, the results of behavioral tests showed that compound 12k could significantly improve learning and memory in vivo. These results suggested that 12k is a promising neuroprotective drug candidate and that the NR2B-NMDA receptor is a potential target of 12k.

5.
J Agric Food Chem ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31509416

RESUMO

Tartary buckwheat (Fagopyrum tataricum) seeds are rich in flavonoids. However, the detailed flavonoid compositions and the molecular basis of flavonoid biosynthesis in tartary buckwheat seeds remain largely unclear. Here, we performed a combined metabolite profiling and transcriptome analysis to identify flavonoid compositions and characterize genes involved in flavonoid biosynthesis in the developing tartary buckwheat seeds. In total, 234 flavonoids, including 10 isoflavones, were identified. Of these, 80 flavonoids were significantly differential accumulation during seed development. Transcriptome analysis indicated that most structural genes and some potential regulatory genes of flavonoid biosynthesis were significantly differentially expressed in the course of seed development. Correlation analysis between transcriptome and metabolite profiling shown that the expression patterns of some differentially expressed structural genes and regulatory genes were more consistent with the changes in flavonoids profiles during seed development, and promoted one SG7 subgroup R2R3-MYB transcription factors (FtPinG0009153900.01) was identified as the key regulatory gene of flavonoid biosynthesis. These findings provide valuable information for understanding the mechanism of flavonoid biosynthesis in tartary buckwheat seeds and the further development of tartary buckwheat health products.

6.
Nat Commun ; 10(1): 4119, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511520

RESUMO

Circular RNAs are non-coding RNAs, and are enriched in the CNS. Dorsal horn neurons of the spinal cord contribute to pain-like hypersensitivity after nerve injury in rodents. Here we show that spinal nerve ligation is associated with an increase in expression of circAnks1a in dorsal horn neurons, in both the cytoplasm and the nucleus. Downregulation of circAnks1a by siRNA attenuates pain-like behaviour induced by nerve injury. In the cytoplasm, we show that circAnks1a promotes the interaction between transcription factor YBX1 and transportin-1, thus facilitating the nucleus translocation of YBX1. In the nucleus, circAnks1a binds directly to the Vegfb promoter, increases YBX1 recruitment to the Vegfb promoter, thereby facilitating transcription. Furthermore, cytoplasmic circAnks1a acts as a miRNA sponge in miR-324-3p-mediated posttranscriptional regulation of VEGFB expression. The upregulation of VEGFB contributes to increased excitability of dorsal horn neurons and pain behaviour induced by nerve injury. We propose that circAnks1a and VEGFB are regulators of neuropathic pain.

7.
Med Phys ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31508827

RESUMO

PURPOSE: Patient body motion during a cardiac Positron Emission Tomography (PET) scan can severely degrade image quality. We propose and evaluate a novel method to detect, estimate, and correct body motion in cardiac PET. METHODS: Our method consists of three key components: motion detection, motion estimation, and motion-compensated image reconstruction. For motion detection, we first divide PET list-mode data into 1-second bins and compute the center of mass (COM) of the coincidences' distribution in each bin. We then compute the covariance matrix within a 25-second sliding window over the COM signals inside the window. The sum of the eigenvalues of the covariance matrix is used to separate the list-mode data into "static" (i.e. body motion free) and "moving" (i.e. contaminated by body motion) frames. Each moving frame is further divided into a number of evenly-spaced sub-frames (referred to as "sub-moving" frames), in which motion is assumed to be negligible. For motion estimation, we first reconstruct the data in each static and sub-moving frame using a rapid back-projection technique. We then select the longest static frame as the reference frame and estimate elastic motion transformations to the reference frame from all other static and sub-moving frames using non-rigid registration. For motion-compensated image reconstruction, we reconstruct all the list-mode data into a single image volume in the reference frame by incorporating the estimated motion transformations in the PET system matrix. We evaluated the performance of our approach in both phantom and human studies. RESULTS: Visually, the motion-corrected (MC) PET images obtained by the proposed method have better quality and fewer motion artifacts than the images reconstructed without motion correction (NMC). Quantitative analysis indicates that MC yields higher myocardium to blood pool concentration ratios. MC also yields sharper myocardium than NMC. CONCLUSION: The proposed body motion correction method improves image quality of cardiac PET.

8.
J Hazard Mater ; 382: 121028, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31473517

RESUMO

The extensive utilization of rigid polyurethane foam (RPUF) as construction insulation material has brought two main troubles to our society: fire risks and toxic hazards. To reduce the fire hazards of RPUF, a layered MoS2 decorated with Cu2O nanoparticles was creativity obtained by hydrothermal technology and facile wet chemical treatment for reducing the toxic product formations of polyurethane nanocomposites during combustion. Due to the low weight ratio of Cu2O attached onto MoS2, the resulting Cu2O-MoS2 hybrid effectively prevented the MoS2 nanosheets from restacking. However, the Cu2O-MoS2-M hybrid was produced by increasing content of Cu2O, which has the characteristic stacked layer structure of MoS2. Reduced harmful organic volatiles and the toxic gases (e.g. a respective decrease of ca. 28% and 53% for CO and NOx products) were obtained because of synergistic effect between the physical adsorption of MoS2 and catalysis action of Cu2O. Notably, the addition of Cu2O-MoS2 hybrids led to high char formation of the RPUF nanocomposite, indicating the effectively catalytic carbonization property. In addition, the N-Gas model for predicting fire smoke toxicity was developed and demonstrated. Furthermore, the research offers direct proofs of the negative influence of the stacked MoS2 on reducing the smoke toxicity for RPUF nanocomposites.

9.
Eur J Med Chem ; 181: 111595, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31408806

RESUMO

A series of benzothiazinones (BTZs) containing an oxime moiety, based on the structure of ZR-10 discovered in our lab, were designed and synthesized. Most of the compounds with alkoxyimino groups attached to the piperazine or cyclohexyl ring of PBTZ169, exhibit excellent in vitro activity against both drug-sensitive and clinically isolated multidrug-resistant Mycobacterium tuberculosis (MTB) strains (MIC: < 0.016-0.037 µg/mL) and low cell cytotoxicity. Two close PBTZ169-analogues 3a and 3b with proper ADME/T and PK properties show potent in vivo efficacy in an acute mouse model of tuberculosis. Compound 3a is under evaluation as a potential clinical candidate for treatment of tuberculosis.

10.
J Am Chem Soc ; 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31436971

RESUMO

Acrylonitriles with aggregation-induced emission (AIE) characteristics have been found to show promising applications in two-photon biomedical imaging. Generally, elaborate synthetic efforts are required to achieve different acrylonitriles with distinct functionalities. In this work, we first reported the synthesis of two different group-functionalized AIE-active acrylonitriles (TPAT-AN-XF and 2TPAT-AN) obtained simply by mixing the same reactants at different temperatures using a facile and transition metal-free synthetic method. These two AIE luminogens (AIEgens) exhibit unique properties such as bright red emission in the solid state, large Stokes shift, and large two-photon absorption cross section. Water-soluble nanoparticles (NPs) of 2TPAT-AN were prepared by a nanoprecipitation method. In vitro imaging data show that 2TPAT-AN NPs can selectively stain lysosome in live cells. Besides one-photon imaging, remarkable two-photon imaging of live tumor tissues can be achieved with high resolution and deep tissue penetration. 2TPAT-AN NPs show high biocompatibility and are successfully utilized in in vivo long-term imaging of mouse tumors with a high signal-to-noise ratio. Thus, the present work is anticipated to shed light on the preparation of a library of AIE-active functionalized acrylonitriles with intriguing properties for biomedical applications.

11.
Biochem Biophys Res Commun ; 518(2): 325-330, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31421824

RESUMO

Exosomes are a type of extracellular vesicles derived from cells and mediators of intercellular communication. Different cell types have their own unique exosomes for exchanging information. We previously found that SASH1, a tumor suppressor, was lowly expressed or absent in glioma tissues and glioma C6 cells, but the structure and function of the corresponding exosomes had been unclear. Hence, we aimed to investigate whether exosomes generated from normal glial cells and glioma cells form different protein patterns and whether those derived from normal glial cells affect SASH1 expression in glioma cells. We collected exosomes from astrocytes and C6 cells and identified their exosomal proteins through mass spectrometry. We also performed gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses, whose results showed that both the total and unique exosomal proteins from each cell type were similar. Moreover, the KEGG analysis revealed different clusters of unique exosomal proteins in glial cells and glioma cells. In the normal glial cells, the top clusters were mainly involved in processes with RNA transcripts and proteins, whereas in glioma cells the clusters were attributed to PI3K-Akt signaling, cell adhesion, and cancer-related pathways. Western blot analysis showed that HMGB1 exists in exosomes derived from cultured astrocytes, although its expression was higher in glioma C6 cells. Furthermore, we found that exosomes extracted from astrocytes could increase SASH1 expression in C6 cells (P = 0.040), whereas those derived from HMGB1-depleted astrocytes could not (P = 0.6133). The expression levels of SASH1 decreased after the addition of extracellular recombinant HMGB1 protein, whereas that of TLR4 increased. Our study is the first to demonstrate that HMGB1 plays different roles depending on its form: as an extracellular protein, HMGB1 decreases SASH1 expression, but as an exosomal protein, HMGB1 increases SASH1 expression. Nevertheless, the mechanism, which partly depends on the TLR4 pathway, behind these opposing effects requires further study. Our novel findings on the structure-dependent roles of the cytokine HMGB1 in promoting or inhibiting cancer provide a fresh insight into the interactions of cancer cells with the microenvironment.

12.
J Orthop Surg Res ; 14(1): 276, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31455401

RESUMO

BACKGROUND: There were several reports describing the biomechanics and microstructure of multifidus muscles in patients with lumbar disc herniation. However, correlations between lumbar multifidus muscle atrophy (LMA), spinopelvic parameters, and severity of adult degenerative scoliosis (ADS) have not been investigated. The study evaluated the impact of LMA and spinopelvic parameters on the severity of ADS. METHODS: One hundred and thirty-two patients with ADS were retrospectively reviewed. Standing whole-spine X-ray was used to evaluate the coronal (coronal Cobb angle, CA; coronal vertical axis, CVA) and sagittal (sagittal vertical axis, SVA; thoracic kyphosis, TK; lumbar lordosis, LL; pelvic incidence, PI; pelvic tilt, PT; sacral slope, SS) parameters. LMA was evaluated on axial T2-weighted magnetic resonance imaging (MRI) at intervertebral levels above and below the vertebra at the apex of the scoliotic curve. Clinical symptoms were evaluated by the Oswestry Disability Index (ODI) and the Japanese Orthopaedic Association (JOA) score. Multiple linear regression was used to assess correlations between LMA, spinopelvic parameters, and severity of scoliosis. RESULTS: LL and PT were negatively correlated with CA (P < 0.001); LL was positively correlated with SVA (P < 0.001). PI was positively correlated with CA (P < 0.001) and CVA (P < 0.001). PT (P < 0.001) and SS (P < 0.001) were negatively correlated with CVA. SS was negatively correlated with SVA (P < 0.001). Concave LMA at the upper or lower intervertebral level of the apical vertebra was positively correlated with CA (P ≤ 0.001); convex LMA at the upper or lower intervertebral level was negatively correlated with CA (P < 0.001). Convex LMA at the upper intervertebral level and concave LMA at the lower intervertebral level of the apical vertebra were negatively correlated with the SVA (P ≤ 0.001). At the upper intervertebral level, LMA on the concave side was positively correlated with CVA (P = 0.028); LMA on the convex side was negatively correlated with CVA (P = 0.012). PI was positively correlated with ODI (P < 0.001); PT (P < 0.001) and SS (P < 0.001) were negatively correlated with ODI. At the lower intervertebral level, LMA on the concave side was positively correlated with ODI (P = 0.038); LMA on the convex side was negatively correlated with ODI (P = 0.011). PI was positively correlated with JOA (P < 0.001); PT (P < 0.001) and SS (P < 0.001) were negatively correlated with JOA. CONCLUSIONS: Spinopelvic parameters are correlated with the severity of ADS. Asymmetric LMA at both upper and lower intervertebral levels of the apical vertebra is positively correlated with CA. LMA on the diagonal through the apical vertebra is very important to maintain sagittal imbalance via parallelogram effect. LMA at lower intervertebral levels of the apical vertebra may have a predictive effect on ODI. JOA score seems to be more correlated with spinopelvic parameters than LMA.

13.
J Recept Signal Transduct Res ; : 1-9, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31466503

RESUMO

Context: Bone mesenchymal stem cells (BMSC)-based regenerative therapy is critical for the craniofacial defect reconstruction. However, oxidative stress micro-environment after transplantation limits the therapeutic efficiency of BMSC. The miR-181c has been found to be associated with cell survival and proliferation. Objective: Herein, we investigated whether prior miR-181c treatment promoted BMSC proliferation and survival under oxidative stress injury. Materials and methods: Cells were treated with hydrogen peroxide (H2O2) and then cell viability was determined via MTT assay, TUNEL staining and ELISA. Western blotting and immunofluorescence assay were used to detect those alterations of mitochondrial function. Results: H2O2 treatment reduced BMSC viability and this effect could be reversed via additional supplementation of miR181-c. Mechanistically, oxidative stress increased cell apoptosis, augmented caspase-3 activity, promoted reactive oxygen species (ROS) synthesis, impaired mitochondrial potential, and induced mitochondrial dynamics imbalance. However, miR-181c pretreatment reversed these effects of oxidative stress on BMSC. Moreover, miR-181c treatment improved BMSC proliferation, migration and paracrine, which are very important for craniofacial reconstruction. In addition, we identified that AMPK-Mfn1 axis was the direct targets of miR-181c in BMSC. Mfn1 silencing impaired the protective effects miR-181c on BMSC viability and proliferation under oxidative stress environment. Conclusions: Collectively, our results indicate that miR-181c participates in oxidative stress-mediated BMSC damage by modulating the AMPK-Mfn1 signaling pathway, suggesting miR-181c-AMPK-Mfn1 axis may serves as novel therapeutic targets to facilitate craniofacial defect reconstruction.

14.
Int J Mol Sci ; 20(16)2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31434233

RESUMO

Root restriction cultivation leads to early maturation and quality improvement, especially in the anthocyanin content in grapevine. However, the molecular mechanisms that underlie these changes have not been thoroughly elucidated. In this study, four small RNA libraries were constructed, which included the green soft stage (GS) and ripe stage (RS) of 'Muscat' (Vitis vinifera L.) grape berries that were grown under root restriction (RR) and in traditional cultivation (no root restriction, CK). A total of 162 known miRNAs and 14 putative novel miRNAs were detected from the four small RNA libraries by high-throughput sequencing. An analysis of differentially expressed miRNAs (DEMs) revealed that 13 miRNAs exhibited significant differences in expression between RR and CK at the GS and RS stages, respectively. For different developmental stages of fruit, 23 and 34 miRNAs showed expression differences between the GS and RS stages in RR and CK, respectively. The expression patterns of the eight DEMs and their targets were verified by qRT-PCR, and the expression profiles of target genes were confirmed to be complementary to the corresponding miRNAs in RR and CK. The function of Vvi-miR828, which showed the down regulated expression in the RS stage under root restriction, was identified by gene transformation in Arabidopsis. The anthocyanin content significantly decreased in transgenic lines, which indicates the regulatory capacity of Vvi-miR828 in fruit coloration. The miRNA expression pattern comparison between RR and CK might provide a means of unraveling the miRNA-mediated molecular process regulating grape berry development under root restricted cultivation.

15.
Chaos ; 29(7): 073119, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31370406

RESUMO

The steady state motion visual evoked potential (SSMVEP)-based brain computer interface (BCI), which incorporates the motion perception capabilities of the human visual system to alleviate the negative effects caused by strong visual stimulation from steady-state VEP, has attracted a great deal of attention. In this paper, we design a SSMVEP-based experiment by Newton's ring paradigm. Then, we use the canonical correlation analysis and Support Vector Machines to classify SSMVEP signals for the SSMVEP-based electroencephalography (EEG) signal detection. We find that the classification accuracy of different subjects under fatigue state is much lower than that in the normal state. To probe into this, we develop a multiplex limited penetrable horizontal visibility graph method, which enables to infer a brain network from 62-channel EEG signals. Subsequently, we analyze the variation of the average weighted clustering coefficient and the weighted global efficiency corresponding to these two brain states and find that both network measures are lower under fatigue state. The results suggest that the associations and information transfer efficiency among different brain regions become weaker when the brain state changes from normal to fatigue, which provide new insights into the explanations for the reduced classification accuracy. The promising classification results and the findings render the proposed methods particularly useful for analyzing EEG recordings from SSMVEP-based BCI system.

16.
Cell Prolif ; : e12667, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31373101

RESUMO

OBJECTIVE: Interstitial fluid in extracellular matrices may not be totally fixed but partially flow through long-distance oriented fibrous connective tissues via physical mechanisms. We hypothesized there is a long-distance interstitial fluid transport network beyond vascular circulations. MATERIALS AND METHODS: We first used 20 volunteers to determine hypodermic entrant points to visualize long-distance extravascular pathway by MRI. We then investigated the extravascular pathways initiating from the point of thumb in cadavers by chest compressor. The distributions and structures of long-distance pathways from extremity ending to associated visceral structures were identified. RESULTS: Using fluorescent tracer, the pathways from right thumb to right atrium wall near chest were visualized in seven of 10 subjects. The cutaneous pathways were found in dermic, hypodermic and fascial tissues of hand and forearm. The perivascular pathways were along the veins of arm, axillary sheath, superior vena cava and into the superficial tissues on right atrium. Histological and micro-CT data showed these pathways were neither blood nor lymphatic vessels but long-distance oriented fibrous matrices, which contained the longitudinally assembled micro-scale fibres consistently from thumb to superficial tissues on right atrium. CONCLUSIONS: These data revealed the structural framework of the fibrous extracellular matrices in oriented fibrous connective tissues was of the long-distance assembled fibres throughout human body. Along fibres, interstitial fluid can systemically transport by certain driving-transfer mechanisms beyond vascular circulations.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31398482

RESUMO

Mycobacterium tuberculosis Beijing genotype strains are widespread globally. However, there has been no systematic study on the associations between Beijing genotype and the characteristics of drug resistance. In this study, we collected 359 M. tuberculosis isolates from south China and investigated their background information, genotype diversity and drug resistance. The results revealed that 66.0% (237/359) of strains were categorized as Beijing genotype. There was no statistical difference between Beijing and non-Beijing genotype strains in terms of sex, age, residence place and treatment history. Drug resistance testing showed that 34.8% (125/359) of isolates were resistant to at least one of the seven drugs tested. The proportions of multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis were 17.0% and 1.4%, respectively. Previously treated patients presented a significantly higher risk of developing drug resistance than new cases. Although the prevalence of drug resistance was observed more frequently in Beijing genotype than in non-Beijing genotype strains, there was no significant difference between these two genotypes. Even in retreated patients, the association of Beijing genotype with drug resistance was not significant. This study provided insight into genotype diversity and demonstrated the characteristics of drug resistance in Beijing genotype strains, which will be useful in generating efficient tuberculosis prevention and control strategies in China.

18.
Front Immunol ; 10: 1643, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379842

RESUMO

Hepatocellular carcinoma (HCC) is a prototype of inflammation-related cancer, harboring M1-like and M2-like tumor-associated macrophages. M1 macrophages are thought to be tumoricidal, but some studies report its pro-tumor role. The programmed cell death-ligand (PD-L) 1 expressed in HCC cells is a critical checkpoint molecule to mediate immune escape of HCC. The PD-L1 expression in HCC cells is inducible. In the present study, we ask whether M1 macrophages induce the expression of PD-L1 in HCC cells. First, an association between M1 macrophage infiltration and PD-L1 expression in HCC tissues was determined by bioinformatics and immunohistochemistry experiments. The enrichment score of M1 macrophages was correlated to PD-L1 expression in 90 HCC samples from GEO database. Besides, infiltration of CD68+HLA-DR+ M1-like macrophages correlated with PD-L1 expression level in HCC cells. Moreover, M1-conditioned media was prepared from M1 macrophages derived from THP-1 cell, RAW264.7 cell or murine bone marrow. These supernatants induced expression of PD-L1 in HCC cells. Furthermore, inflammatory cytokine IL-1ß in the supernatants was identified to account for the inducible PD-L1 expression by siRNA assay and receptor blockade assay. Additionally, transcription factor p65 and IRF1 in the HCC cells were revealed by CHIP assay to mediate the inducible PD-L1 expression. All the results demonstrate that M1 macrophages induced expression of PD-L1 in HCC cells, supporting the pro-tumor role of M1 macrophages.

19.
Phys Med Biol ; 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31394518

RESUMO

Motion of the myocardium deteriorates the quality and quantitative accuracy of cardiac PET images. We present a method for MR-based cardiac and respiratory motion correction of cardiac PET data and evaluate its impact on estimation of activity and kinetic parameters in human subjects. Three healthy subjects underwent simultaneous dynamic &lt;sup&gt;18&lt;/sup&gt;F-FDG PET and MRI on a hybrid PET/MR scanner. A cardiorespiratory motion field was determined for each subject using navigator, tagging and golden-angle radial MR acquisitions. Acquired coincidence events were binned into cardiac and respiratory phases using electrocardiogram and list mode-driven signals, respectively. Dynamic PET images were reconstructed with MR-based motion correction (MC) and without motion correction (NMC). Parametric images of &lt;sup&gt;18&lt;/sup&gt;F-FDG consumption rates (K&lt;sub&gt;i&lt;/sub&gt;) were estimated using Patlak's method for both MC and NMC images. MC alleviated motion artifacts in PET images, resulting in improved spatial resolution, improved recovery of activity in the myocardium wall and reduced spillover from the myocardium to the left ventricle cavity. Significantly higher myocardium contrast-to-noise ratio and lower apparent wall thickness were obtained in MC versus NMC images. Likewise, parametric images of K&lt;sub&gt;i&lt;/sub&gt; calculated with MC data had improved spatial resolution as compared to those obtained with NMC. Consistent with an increase in reconstructed activity concentration in the frames used during kinetic analyses, MC led to the estimation of higher K&lt;sub&gt;i&lt;/sub&gt; values almost everywhere in the myocardium, with up to 18% increase (mean across subjects) in the septum as compared to NMC. This study shows that MR-based motion correction of cardiac PET results in improved image quality that can benefit both static and dynamic studies.

20.
Zhongguo Fei Ai Za Zhi ; 22(7): 427-432, 2019 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-31315781

RESUMO

BACKGROUND: DNA polymerase ß is one of the key enzymes for DNA repair and it was reported that about 30 percent of different types of cancers carried mutations in its coding gene Polb. However, it is still controversial whether it is true or false because of the small sample size in these studies. In current study, we performed genetic screening of promoter and coding regions of Polb gene in 69 Chinese lung cancer patients using Sanger sequencing method, so as to elucidate real mutation frequency of Polb mutations in Chinese Han population. METHODS: Salting out extraction method was used to get the genome DNAs from tumor and normal matched tissues of 69 lung cancer patients. The promoter and 14 coding regions of Polb gene were then amplified using these DNAs as the template. After purification, amplicons were sequenced and aligned to the wild type Polb gene in NCBI database, in order to find out the mutated sites of Polb gene in Chinese lung cancer patients. RESULTS: In this study, we totally found only 5 mutated sites in Polb gene. In detail, 3 mutations (-196G>T, -188_-187insCGCCC, -168C>A) were located in the promoter region; 2 mutations (587C>G, 612A>T) were found in coding regions. Specially, mutations of -188_-187insCGCCC and 587C>G (resulting to the amino acid substitution of Thr to Ser at position 196) had never been reported by other groups before. However, all these 5 mutated sites could be detected in both tumor and matched normal tissues, which inferred that they are not lung tumor specific mutations. CONCLUSIONS: No lung tumor specific mutations of Polb gene could be found in Chinese lung cancer patients and Polb gene mutation might not be a molecular marker for Chinese lung cancer patients.

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