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1.
Neural Regen Res ; 16(1): 93-98, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32788452

RESUMO

Peripheral nerve injury (PNI) is common and, unlike damage to the central nervous system injured nerves can effectively regenerate depending on the location and severity of injury. Peripheral myelinating glia, Schwann cells (SCs), interact with various cells in and around the injury site and are important for debris elimination, repair, and nerve regeneration. Following PNI, Wallerian degeneration of the distal stump is rapidly initiated by degeneration of damaged axons followed by morphologic changes in SCs and the recruitment of circulating macrophages. Interaction with fibroblasts from the injured nerve microenvironment also plays a role in nerve repair. The replication and migration of injury-induced dedifferentiated SCs are also important in repairing the nerve. In particular, SC migration stimulates axonal regeneration and subsequent myelination of regenerated nerve fibers. This mobility increases SC interactions with other cells in the nerve and the exogenous environment, which influence SC behavior post-injury. Following PNI, SCs directly and indirectly interact with other SCs, fibroblasts, and macrophages. In addition, the inter- and intracellular mechanisms that underlie morphological and functional changes in SCs following PNI still require further research to explain known phenomena and less understood cell-specific roles in the repair of the injured peripheral nerve. This review provides a basic assessment of SC function post-PNI, as well as a more comprehensive evaluation of the literature concerning the SC interactions with macrophages and fibroblasts that can influence SC behavior and, ultimately, repair of the injured nerve.

2.
Methods Mol Biol ; 2180: 351-361, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32797420

RESUMO

Raman spectroscopy has been gaining in popularity for noninvasive analysis of single cells. Raman spectra and images deliver meaningful information regarding the biochemical, biophysical, and structural properties of cells in various states. Low-temperature Raman spectroscopy has been applied to verify the presence of ice inside a frozen cell and to illustrate the distribution of both penetrating and non-penetrating cryoprotectants. This chapter delineates Raman cryomicroscopic imaging of single cells as well as sample handling for spectroscopic measurements at subzero temperature. The experimental setup is depicted with a special emphasis on a custom-built temperature-controlled cooling stage. The use of Raman cryomicroscopic imaging is demonstrated using Jurkat cells cryopreserved in a sucrose solution. Moreover, strategies for determining intracellular ice formation (IIF) and analysis of sucrose partitioning across the cell membrane are presented.

3.
Spectrochim Acta A Mol Biomol Spectrosc ; 244: 118845, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-32882656

RESUMO

A functional ratio fluorescence sensor based on the molecularly imprinted polymer (MIP) coated double quantum dots (QDs) being composited of Mn-ZnS QDs and silica-coated graphene quantum dots (GQDs@SiO2) had been established for the sensitive, selective and visual detection of sinapic acid (SA). MIPs@Mn-ZnS/GQDs@SiO2 was synthesized through a simple one-pot sol-gel reaction, and it exhibited two fluorescence emission peaks with yellow fluorescence of Mn-ZnS QDs at 580 nm and the blue fluorescence of GQDs at 445 nm. SA can selectively enhance the fluorescence of GQDs but quench the Mn-ZnS QDs fluorescence to the MIPs@Mn-ZnS/GQDs@SiO2. The ratio of fluorescence enhancement to fluorescence reduction is linear with the concentration of SA from 9 to 81 nM with the detection limits of 0.8388 nM (S/N = 3). And the constructed fluorescent probe can also be used to visually detect SA according to the change of color. More importantly, molecular imprinting technique enables the sensors to selectively recognize the SA while other similar structure molecules hardly interfere with the SA determination in the measurement environment. Meanwhile, the fluorescence sensors have the advantages of fast response time and long duration of fluorescence intensity. These excellent performances made the proposed method to be applied for the determination of SA in Semen Sinapis and Descurainiae Semen.

4.
Genes Dev ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004416

RESUMO

EBF1 and PAX5 mutations are associated with the development of B progenitor acute lymphoblastic leukemia (B-ALL) in humans. To understand the molecular networks driving leukemia in the Ebf1+/-Pax5+/- (dHet) mouse model for B-ALL, we interrogated the transcriptional profiles and chromatin status of leukemic cells, preleukemic dHet pro-B, and wild-type pro-B cells with the corresponding EBF1 and Pax5 cistromes. In dHet B-ALL cells, many EBF1 and Pax5 target genes encoding pre-BCR signaling components and transcription factors were down-regulated, whereas Myc and genes downstream from IL-7 signaling or associated with the folate pathway were up-regulated. We show that blockade of IL-7 signaling in vivo and methotrexate treatment of leukemic cells in vitro attenuate the expansion of leukemic cells. Single-cell RNA-sequencing revealed heterogeneity of leukemic cells and identified a subset of wild-type pro-B cells with reduced Ebf1 and enhanced Myc expression that show hallmarks of dHet B-ALL cells. Thus, EBF1 and Pax5 may safeguard early stage B cells from transformation to B-ALL by limiting IL-7 signaling, folate metabolism and Myc expression.

5.
Inorg Chem ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021788

RESUMO

In this paper, the hyperkagome lattice of Gd spins in a garnet compound, Gd3CrGa4O12, is studied using bulk measurements and density functional computations, and the observation of large magnetocaloric effect corresponding to an entropy change, ΔSm = 45 J kg-1K-1 (≈ 45 J mol-1K-1) at 2 K, 8 T is reported. Though the compound defies long-range magnetic order down to 0.4 K, a broad feature below 10 K is observed in the specific heat with two low temperature anomalies at T* ≈ 0.7 K and TS ≈ 2.45 K. The anomaly at T* is reminiscent of one in Gd3Ga5O12, where it is related to the development of a complex magnetic phase, whereas the TS-peak is accounted for by a multilevel Schottky-like model. The spin-lattice relaxation times studied by nuclear magnetic resonance experiments show that the relaxation is dominated by the magnetic fluctuations in Cr which has a longer relaxation time compared to that of the garnet, Lu3CrGa4O12 containing a nonmagnetic rare earth. Our first-principles density functional theory calculations agree well with the experimental results and support short-range magnetic order in the Gd-sublattice and antiferromagnetism in the Cr-sublattice. The importance of spin fluctuations and short-range order in the rare earth and transition metal lattices in garnets resulting in large magnetocaloric effect is brought out through this work.

6.
Genes (Basel) ; 11(10)2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33023248

RESUMO

Over the past decade, a large amount of RNA sequencing (RNA-seq) data were deposited in public repositories, and more are being produced at an unprecedented rate. However, there are few open source tools with point-and-click interfaces that are versatile and offer streamlined comprehensive analysis of RNA-seq datasets. To maximize the capitalization of these vast public resources and facilitate the analysis of RNA-seq data by biologists, we developed a web application called OneStopRNAseq for the one-stop analysis of RNA-seq data. OneStopRNAseq has user-friendly interfaces and offers workflows for common types of RNA-seq data analyses, such as comprehensive data-quality control, differential analysis of gene expression, exon usage, alternative splicing, transposable element expression, allele-specific gene expression quantification, and gene set enrichment analysis. Users only need to select the desired analyses and genome build, and provide a Gene Expression Omnibus (GEO) accession number or Dropbox links to sequence files, alignment files, gene-expression-count tables, or rank files with the corresponding metadata. Our pipeline facilitates the comprehensive and efficient analysis of private and public RNA-seq data.

7.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 4620-4623, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33019023

RESUMO

Wearable body area networks (BANs) have been widely used in activity measurements for kinematic information collection. This paper presents the design and implementation of a wearable device used as a training tool in freestyle swimming. The device supplies a close-loop control mechanism via a fuzzy logic controller. Swimming posture data is collected quantitatively and audibly fed back to swimmers in real time through bone conductors. Two recreational swimmers were invited to participate in a series of experiments including 7 days of baseline capability test (no feedback), 7 days of feedback training, and 2 days of retention test. It was found that both swimmers could well adapt to the feedback instructions. A maximum of 7.62% of lap time improvement and 29.64% of trunk roll improvement were observed in FB training, and such pattern was maintained after feedback was removed. We conclude that real-time fuzzy logic feedback can be used to improve recreational swimmers performance.

8.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5557-5562, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33019237

RESUMO

The prevalence of personal health data from wearable devices enables new opportunities to understand the impact of behavioral factors on health. Unlike consumer devices that are often auxiliary, such as Fitbit and Garmin, wearable medical devices like continuous glucose monitoring (CGM) devices and insulin pumps are becoming critical in diabetes care to minimize the occurrence of adverse glycemic events. Joint analysis of CGM and insulin pump data can provide unparalleled insights on how to modify treatment regimen to improve diabetes management outcomes. In this paper, we employ a data-driven approach to study the relationship between key behavioral factors and proximal diabetic management indicators. Our dataset includes an average of 161 days of time-matched CGM and insulin pump data from 34 subjects with Type 1 Diabetes (T1D). By employing hypothesis testing and association mining, we observe that smaller meals and insulin doses are associated with better glycemic outcomes compared to larger meals and insulin doses. Meanwhile, the occurrence of interrupted sleep is associated with poorer glycemic outcomes. This paper introduces a method for inferring disrupted sleep from wearable diabetes-device data and provides a baseline for future research on sleep quality and diabetes. This work also provides insights for development of decision-support tools for improving short- and long-term outcomes in diabetes care.

9.
BMJ Open ; 10(10): e032833, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046460

RESUMO

OBJECTIVE: This study aimed to investigate the relationship between birth order and stereoacuity among Chinese children aged 60-72 months. DESIGN: Cross-sectional. PARTICIPANTS: 1342 children with complete data on the questionnaire, stereoacuity and refraction were included. RESULTS: The mean stereoacuity was 53.2±1.7, 56.9±1.9 and 60.9±1.5 s of arc in the first-born group, second-born group and third-born group, respectively. Lower birth order was significantly correlated with better stereoacuity (p=0.036). Third-borns (OR=3.02, p=0.027) were at higher risk of having subnormal stereoacuity compared with first-borns in the multivariate analysis. CONCLUSION: Later-borns had poorer stereoacuity than first-borns.

10.
Cell Biochem Funct ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33047358

RESUMO

MiR-140-5p is high expressed in normal fracture healing, but its specific role and mechanism in tissue-to-bone healing are rarely reported. Therefore, this study investigated the effects of miR-140-5p on tissue-to-bone healing. Clone formation experiment, flow cytometry, Alizarin Red S Staining and Oil Red O Staining were performed to investigate the biological characteristics of mouse embryonic bone marrow mesenchymal stem cells C3H10T1/2. MiR-140-5p mimic was transfected into osteogenic medium (OS)-treated C3H10T1/2 cells to investigate the effects of miR-140-5p on osteogenic differentiation. MiR-140-5p transgenic mouse model and the transgenic fracture model were established, and the effects of miR-140-5p on osteogenic differentiation, bone mineral density (BMD) and bone mass of bone tissues were detected by haematoxylin and eosin staining and computed tomography scan. The expressions of osteocalcin, differentiation-related genes (Runx2, ALP, Spp1 and Bglap3) and miR-140-5p were determined by quantitative real-time polymerase chain reaction. C3H10T1/2 cells showed the abilities of forming cloned differentiation of osteogenesis, fat cells, and its phenotypes including CD44, CD90.1 and Sca-1 but excluding CD45 haematopoietic stem cell marker. Overexpression of miR-140-5p promoted the expressions of differentiation-related genes and calcium deposition of OS-treated C3H10T1/2 cells. MiR-140-5p increased the expression of osteocalcin, BMD and bone mass and promoted bone healing of miR-140-5p-transgenic mice with fracture. MiR-140-5p promoted osteogenic differentiation of mouse embryonic bone marrow mesenchymal stem cells and post-fracture healing in mice. SIGNIFICANCE OF THE STUDY: C3H10T1/2 cells showed the abilities of forming cloned differentiation of osteogenesis, fat cells and its phenotypes including CD44, CD90.1 and Sca-1 but excluding CD45 haematopoietic stem cell marker. Overexpression of miR-140-5p promoted the expressions of differentiation-related genes and calcium deposition of osteogenic medium-treated C3H10T1/2 cells. MiR-140-5p increased the expression of osteocalcin and bone mineral density and bone mass and promoted bone healing of miR-140-5p-transgenic mice with fracture. Our results showed that miR-140-5p promoted osteogenic differentiation of mouse embryonic bone marrow mesenchymal stem cells and post-fracture healing in mice, which may be a therapeutic target for treating fractures and promoting bone healing.

11.
Int J Cosmet Sci ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33048363

RESUMO

OBJECTIVES: Retinoids have been used for decades as efficacious topical agents to treat photoaged skin. The purpose of our present research is to evaluate whether the activity of the Vitamin A ester retinyl propionate (RP) can be enhanced by niacinamide (Nam) and a flavonoid containing Ceratonia siliqua (CS) fruit extract in retinoid responsive in vitro models. METHODS: RP was tested alone and in combination with Nam and CS in an RARa reporter cell line for promoter activation and compared to trans-retinoic acid (tRA) activation. These treatments were also tested in keratinocytes for gene expression profiling by qPCR using a panel of 40 retinoid responsive genes. RESULTS: tRA or RP elicited RARa reporter activation in a dose dependent manner. The combination of 0.5 mM or 2 mM RP with 10 mM Nam had a 56% and 95% signal increase compared to RP, respectively. The addition of 1% CS to 0.5 mM or 2 mM RP with 10 mM Nam elicited a further increase of 114% and 156%, respectively, over RP and Nam combinations. All retinoids elicited an increase in expression of 40 retinoid sensitive genes over control levels. Of the 40 genes 27 were enhanced by either 0.1 mM RP or 0.5 mM RP with 10 mM Nam and 1% CS. Nam or CS had very modest activity in both models. CONCLUSION: The combination of RP with Nam and CS showed a higher retinoid response than RP in two separate retinoid responsive in vitro models. We hypothesize Nam and CS enhances RP activity by modulating metabolism to tRA via increasing NAD+ pools and inhibiting reduction of retinal (RAL) back to retinol, respectively. The findings provide evidence that this combination may have enhanced efficacy for treating the appearance of photoaged skin.

12.
Cell Rep ; 33(1): 108223, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33027655

RESUMO

Overweight and obesity are associated with type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular disease and cancer, but all fat is not equal, as storing excess lipid in subcutaneous white adipose tissue (SWAT) is more metabolically favorable than in visceral fat. Here, we uncover a critical role for mTORC2 in setting SWAT lipid handling capacity. We find that subcutaneous white preadipocytes differentiating without the essential mTORC2 subunit Rictor upregulate mature adipocyte markers but develop a striking lipid storage defect resulting in smaller adipocytes, reduced tissue size, lipid re-distribution to visceral and brown fat, and sex-distinct effects on systemic metabolic fitness. Mechanistically, mTORC2 promotes transcriptional upregulation of select lipid metabolism genes controlled by PPARγ and ChREBP, including genes that control lipid uptake, synthesis, and degradation pathways as well as Akt2, which encodes a major mTORC2 substrate and insulin effector. Further exploring this pathway may uncover new strategies to improve insulin sensitivity.

13.
Int J Med Sci ; 17(16): 2511-2530, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029094

RESUMO

ShuFeng JieDu capsule (SFJDC), a traditional Chinese medicine, has been recommended for the treatment of COVID-19 infections. However, the pharmacological mechanism of SFJDC still remains vague to date. The active ingredients and their target genes of SFJDC were collected from TCMSP. COVID-19 is a type of Novel Coronavirus Pneumonia (NCP). NCP-related target genes were collected from GeneCards database. The ingredients-targets network of SFJDC and PPI networks were constructed. The candidate genes were screened by Venn diagram package for enrichment analysis. The gene-pathway network was structured to obtain key target genes. In total, 124 active ingredients, 120 target genes of SFJDC and 251 NCP-related target genes were collected. The functional annotations cluster 1 of 23 candidate genes (CGs) were related to lung and Virus infection. RELA, MAPK1, MAPK14, CASP3, CASP8 and IL6 were the key target genes. The results suggested that SFJDC cloud be treated COVID-19 by multi-compounds and multi-pathways, and this study showed that the mechanism of traditional Chinese medicine (TCM) in the treatment of disease from the overall perspective.


Assuntos
Antivirais/farmacologia , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Pneumonia Viral/tratamento farmacológico , Mapas de Interação de Proteínas/efeitos dos fármacos , Antivirais/química , Cápsulas/farmacologia , Caspase 3/genética , Caspase 8/genética , Infecções por Coronavirus/genética , Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-6/genética , Proteína Quinase 1 Ativada por Mitógeno/genética , Pandemias , Pneumonia Viral/genética , Mapas de Interação de Proteínas/genética , Fator de Transcrição RelA/genética
14.
Int J Nanomedicine ; 15: 7013-7034, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061365

RESUMO

Purpose: Gastric cancer stem cells (CSCs) are important for the initiation, growth, recurrence, and metastasis of gastric cancer, due to their chemo-resistance and indefinite proliferation. Herein, to eliminate gastric CSCs, we developed novel CSC-targeting glioma-associated oncogene homolog 1 (Gli1) small interfering RNA (siRNA) nanoparticles that are specifically guided by a di-stearoyl-phosphatidyl-ethanolamine- hyaluronic-acid (DSPE-HA) single-point conjugate, as an intrinsic ligand of the CD44 receptor. We refer to these as targeting Gli1 siRNA nanoparticles. Methods: We used the reductive amination reaction method for attaching amine groups of DSPE to aldehydic group of hyaluronic acid (HA) at the reducing end, to synthesize the DSPE-HA single-point conjugate. Next, targeting Gli1 siRNA nanoparticles were prepared using the layer-by-layer assembly method. We characterized the stem cellular features of targeting Gli1 siRNA nanoparticles, including their targeting efficiency, self-renewal capacity, the migration and invasion capacity of gastric CSCs, and the penetration ability of 3D tumor spheroids. Next, we evaluated the therapeutic efficacy of the targeting Gli1 siRNA nanoparticles by using in vivo relapsed tumor models of gastric CSCs. Results: Compared with the multipoint conjugates, DSPE-HA single-point conjugates on the surface of nanoparticles showed significantly higher binding affinities with CD44. The targeting Gli1 siRNA nanoparticles significantly decreased Gli1 protein expression, inhibited CSC tumor spheroid and colony formation, and suppressed cell migration and invasion. Furthermore, in vivo imaging demonstrated that targeting Gli1 siRNA nanoparticles accumulated in tumor tissues, showing significant antitumor recurrence efficacy in vivo. Conclusion: In summary, our targeting Gli1 siRNA nanoparticles significantly inhibited CSC malignancy features by specifically blocking Hedgehog (Hh) signaling both in vitro and in vivo, suggesting that this novel siRNA delivery system that specifically eliminates gastric CSCs provides a promising targeted therapeutic strategy for gastric cancer treatment.

15.
Biomed Res Int ; 2020: 8469560, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33062702

RESUMO

Objective: To understand how to implement proactive prevention measures among healthcare professionals for preventing potential nosocomial infection. Methods: 91 healthcare professionals confirmed with the COVID-19 infection were collected, and clinical characteristics and epidemiological data were evaluated. Results: Among the cases, 77 cases (84.6%) were confirmed by the viral nucleic acid test, and the other 14 cases were diagnosed by the clinical investigation. Ground glass opacity and bilateral shadows distribution were observed in 78 cases (85.6%). 56 cases (61.5%) were admitted into Zhongnan Hospital and subjected to antiviral treatment. 73 of a total of 91 cases (80.2%) with a median incubation period of 3 days (IQR, 2 to 6) reported close contact history with patients with the COVID-19 infection. The most common symptoms at the onset of illness were fever (66 cases, 72.5%) and cough (54 cases, 59.3%). The initial positive rate of the CT scan and RT-PCR assay were 84.6% and 48.4%, respectively (P < 0.01). There were 50 cases occurred during the early stage (before Jan 20, 2020), whereas 41 cases occurred at a late stage (after Jan 20, 2020). In the early stage, the most common route of exposure to COVID-19 was via direct care in the absence of any invasive procedure. By contrast, 37 healthcare professionals infected with COVID-19 in the late stage were confirmed to have been exposed via aerosol-generating procedures. Conclusion: Identification of the asymptomatic individuals in healthcare settings and prompt response when a suspicious case is considered may render effective control of the nosocomial infection during this pandemic.

16.
Transfus Med ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33000534

RESUMO

OBJECTIVE: The COVID-19 epidemic has caused a significant global social and economic impact since December 2019. The objective of this study was to demonstrate the emergency response of a Chinese blood centre on maintaining both the safety and the sufficiency of blood supply during large, emerging, infectious epidemics. MATERIALS AND METHODS: Early on in the outbreak of COVID-19, the Chengdu Blood Center developed strategies and implemented a series of measures, including enhanced recruitment efforts, addition of new donation deferral criteria and notification after donation, optimisation of donor experience, development and implementation of a new coronavirus nucleic acid detection technology platform for blood screening and screening all donations for SARS-CoV-2 RNA to maximumly protect the safety of blood supply during a time of unclear risk. RESULTS: Starting on February 20, the immediate satisfaction rate of blood product orders in Chengdu city's clinical settings reached 100%, and there was no case of blood transfusion infection. CONCLUSION: The recent experience during the outbreak of SARS-CoV-2 reminded us that improvement in the areas of national and international collaborative programmes for dealing with blood availability and safety concerns during early stages of a disaster and regional and national mechanisms for timely communication with the general public on behalf of blood services should help to better prepare us for future disasters.

17.
Int J Med Sci ; 17(16): 2427-2439, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029085

RESUMO

Background and aim: Competing endogenous RNA (ceRNA) is believed to play vital roles in tumorigenesis. The goal of this study was to screen prognostic biomarkers in lung adenocarcinoma (LUAD). Methods: Common differentially expressed genes (DEGs) were collected from Gene Expression Omnibus (GEO) databases and The Cancer Genome Atlas databases (TCGA) using GEO2R and "limma" package in R, respectively. Overlapping DEGs were conducted using enrichment of functions and protein-protein interaction (PPI) network to discover significant candidate genes. By using a comprehensive analysis, we constructed an mRNA mediated ceRNA network. Survival rates were used Kaplan-Meier analysis. Statistical analysis was used to further identify the prognosis of studied genes. Results: Integrated analysis of GSE32863 and TCGA databases, a total of 886 overlapping DEGs, including 279 up-regulated and 607 down-regulated genes were identified. Considering the highest term of candidate genes in PPI, we identified TPX2, which was enriched in cell division signaling pathway. Besides, 35 differentially expressed miRNAs (DEmiRNAs) were predicted to target TPX2 and only 7 DEmiRNAs were identified to be prognostic biomarkers in LUAD. Then, 30 differentially expressed lncRNAs (DElncRNAs) were predicted to bind these 7 DEmiRNAs. Finally, we found that 7 DElncRNAs were correlated with the overall survival (all p <0.05). Furthermore, we identified elevated TPX2 was strongly correlated with the worse survival rate among 458 samples. Univariate and multivariate cox analysis showed TPX2 may act as an independent factor for prognosis in LUAD (p <0.05). Then pathway enrichment results suggested that TPX2 may facilitate tumorigenesis by participating in several cancer-related signaling pathways in LUAD, especially in Notch signal pathway. Conclusions: TPX2-related lncRNAs and miRNAs are related to the survival of LUAD. 7 lncRNAs, 7 miRNAs and TPX2 may serve as prognostic biomarkers in LUAD.

18.
Arterioscler Thromb Vasc Biol ; : ATVBAHA120315288, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33028099

RESUMO

OBJECTIVE: To determine the bilaterally asymmetrical associations between extracranial carotid artery atherosclerosis and ipsilateral middle cerebral artery (MCA) stenosis in symptomatic patients using magnetic resonance vessel wall imaging. Approach and Results: Patients with symptomatic carotid artery atherosclerosis were recruited from the Chinese Atherosclerosis Risk Evaluation, a multicenter study. All subjects underwent intracranial magnetic resonance angiography and extracranial carotid artery magnetic resonance imaging. Severe stenosis (stenosis ≥50%) of MCA, carotid moderate-to-severe stenosis (stenosis ≥50%), plaque compositions, and high-risk plaque on symptomatic side were evaluated in all subjects. Associations between ipsilateral MCA stenosis and extracranial carotid plaque features were evaluated. A total of 363 patients (mean age: 61.2±10.4 years old; 254 males) were included. In the left symptomatic cerebrovascular group (n=186), carotid moderate-to-severe stenosis (odds ratio [OR], 3.00 [95% CI, 1.03-8.79]; P=0.045), intraplaque hemorrhage (OR, 3.68 [95% CI, 1.21-11.19]; P=0.021), fibrous cap rupture (OR, 5.70 [95% CI,1.60-20.31]; P=0.007), and high-risk plaque (OR, 2.95 [95% CI, 1.19-7.35]; P=0.020) were significantly associated with ipsilateral severe MCA stenosis, after adjusting for confounding factors. In the right symptomatic cerebrovascular group (n=177), severe MCA stenosis was significantly associated with ipsilateral carotid moderate-to-severe stenosis (OR, 3.98 [95% CI, 1.54-10.32]; P=0.004) but not with other extracranial carotid plaque features (all P>0.05), after adjusting for confounding factors. CONCLUSIONS: In the symptomatic arteries, vulnerable plaque features are independently associated with ipsilateral severe MCA stenosis on the left side, but this association is not found on the right side, indicating the associations of atherosclerotic disease between intracranial and extracranial carotid arteries are asymmetrical.

19.
Immunity ; 53(4): 805-823.e15, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33053330

RESUMO

The activating receptor CD226 is expressed on lymphocytes, monocytes, and platelets and promotes anti-tumor immunity in pre-clinical models. Here, we examined the role of CD226 in the function of tumor-infiltrating lymphocytes (TILs) and resistance to immunotherapy. In murine tumors, a large proportion of CD8+ TILs had decreased surface expression of CD226 and exhibited features of dysfunction, whereas CD226hi TILs were highly functional. This correlation was seen also in TILs isolated from HNSCC patients. Mutation of CD226 at tyrosine 319 (Y319) led to increased CD226 surface expression, enhanced anti-tumor immunity and improved efficacy of immune checkpoint blockade (ICB). Mechanistically, tumor-derived CD155, the ligand for CD226, initiated phosphorylation of Y319 by Src kinases, thereby enabling ubiquitination of CD226 by CBL-B, internalization, and proteasomal degradation. In pre-treatment samples from melanoma patients, CD226+CD8+ T cells correlated with improved progression-free survival following ICB. Our findings argue for the development of therapies aimed at maintaining the expression of CD226.

20.
Psychiatry Res Neuroimaging ; : 111203, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33051064

RESUMO

Apathy is one of the core symptoms in behavioral variant of frontotemporal dementia (bvFTD), and increases patient's morbidity and caregiver's distress. In this study, we applied a graph theoretical analysis (GTA) to analyze the topological properties of cerebral blood flow (CBF) network in 64 bvFTD patients with and without apathy (47 bvFTD-apathy and 17 bvFTD-woapathy, respectively), and 20 normal controls (NCs) based on single photon emission tomography (SPECT). Compared with the NCs, both the bvFTD groups preserved global function and typical features of small-worldness, but exhibited the loss of hubs mainly distributed in the prefrontal cortex (PFC). Compared with bvFTD-woapathy, the bvFTD-apathy group exhibited additional loss of hubs in the ventral PFC areas, middle cingulate cortex, limbic and paralimbic system, and subcortical regions, but recruited hubs in the areas of angular gyrus, precuneus and posterior cingulate cortex. Overall, our findings support the hypothesis that the disruption of frontostriatal circuit is associated with apathy in bvFTD.

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