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1.
Front Immunol ; 11: 1281, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32765489

RESUMO

Background: The tumor microenvironment (TME) of human glioblastoma (GBM) exhibits considerable immune cell infiltration, and such cell types have been shown to be widely involved in the development of GBM. Here, weighted correlation network analysis (WGCNA) was performed on publicly available datasets to identify immune-related molecules that may contribute to the progression of GBM and thus be exploited as potential therapeutic targets. Methods: WGCNA was used to identify highly correlated gene clusters in Chinese Glioma Genome Atlas glioma dataset. Immune-related genes in significant modules were subsequently validated in the Cancer Genome Atlas (TCGA) and Rembrandt databases, and impact on GBM development was examined in migration and vascular mimicry assays in vitro and in an orthotopic xenograft model (GL261 luciferase-GFP cells) in mice. Results: WGCNA yielded 14 significant modules, one of which (black) contained genes involved in immune response and extracellular matrix formation. The intersection of these genes with a GO immune-related gene set yielded 47 immune-related genes, five of which exhibited increased expression and association with worse prognosis in GBM. One of these genes, TREM1, was highly expressed in areas of pseudopalisading cells around necrosis and associated with other proteins induced in angiogenesis/hypoxia. In macrophages induced from THP1 cells, TREM1 expression levels were increased under hypoxic conditions and associated with markers of macrophage M2 polarization. TREM1 siRNA knockdown in induced macrophages reduced their ability to promote migration and vascular mimicry in GBM cells in vitro, and treatment of mice with LP-17 peptide, which blocks TREM1, inhibited growth of GL261 orthotopic xenografts. Finally, blocking the cytokine receptor for CSF1 in induced macrophages also impeded their potential to promote tumor migration and vascular mimicry in GBM cells. Conclusions: Our results demonstrated that TREM1 could be used as a novel immunotherapy target for glioma patients.

2.
Am J Hypertens ; 2020 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-32710605

RESUMO

Accumulating evidence demonstrates that blood pressure variability (BPV) may contribute to target organ damage, causing coronary heart disease, stroke, and renal disease independent of the level of BP. Several lines of evidence have also linked increased BPV to a higher risk of cognitive decline and incident dementia. The estimated number of dementia cases worldwide is nearly 50 million, and this number continues to grow with increasing life expectancy. Because there is no effective treatment to modify the course of dementia, targeting modifiable vascular factors continues as a top priority for dementia prevention. A clear understanding of the role of BPV in dementia may shed light on the etiology, early prevention, and novel therapeutic targets of dementia, and has therefore gained substantial attention from researchers and clinicians. This review summarizes state-of-art evidence on the relationship between BPV and dementia, with a specific focus on the epidemiological evidence, the underlying mechanisms, and potential intervention strategies. We also discuss challenges and opportunities for future research to facilitate optimal BP management and the clinical translation of BPV for the risk assessment and prevention of dementia.

3.
Nanomaterials (Basel) ; 10(7)2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32708603

RESUMO

A Bragg-mirror-assisted terahertz (THz) high-contrast and broadband plasmonic interferometer is proposed and theoretically investigated for potential sensing applications. The central microslit couples the incident THz wave into unidirectional surface plasmon polaritons (SPPs) waves travelling to the bilateral Bragg gratings, where they are totally reflected over a wide wavelength range back towards the microslit. The properties of interference between the SPPs waves and transmitted THz wave are highly dependent on the surrounding material, offering a flexible approach for the realization of refractive index (RI) detection. The systematic study reveals that the proposed interferometric sensor possesses wavelength sensitivity as high as 167 µm RIU-1 (RIU: RI unit). More importantly, based on the intensity interrogation method, an ultrahigh Figure-of-Merit (FoM) of 18,750% RIU-1, surpassing that of previous plasmonic sensors, is obtained due to the high-contrast of interference pattern. The results also demonstrated that the proposed sensors are also quite robust against the oblique illumination. It is foreseen the proposed configuration may open up new horizons in developing THz plasmonic sensing platforms and next-generation integrated THz circuits.

4.
Int J Med Sci ; 17(10): 1406-1414, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32624697

RESUMO

Adoptive cellular immunotherapy employing chimeric antigen receptors-modified T (CAR-T) cells has demonstrated promising antitumor effects in hematologic cancers. However, CAR-T therapy confront many challenges in solid tumors like immunosuppressive microenvironment, molecular heterogeneity, etc. The cancer genome atlas (TCGA) of hepatocellular carcinoma (HCC) revealed many genetic characteristic and molecular tumorigenesis. EGFRvIII is a tumor specific antigen widely expressed in a variety of cancers including HCC and an ideal therapeutic target for cancer therapy. The liver cancer cell line SMMC7721 express high level EGFRvIII and widely applied in HCC investigations. Herein, we developed EGFRvIII CAR-T cells by piggyBac transposon system, and detected its specific killing effect against SMMC7721 cells in vitro and in vivo. Results indicated that transduction efficiency of CAR reached 53.1%. Expression of CAR protein was verified by immunoblotting as a band of approximate 57KD. The killing effect of CAR-T cells against SMMC7721 was positively correlated with E/T ratio (E:T=5:1, 10:1, 20:1, 40:1), and exceeded 50% at 20:1 ratio. Significant increase in IFN-γ and TNF-α secretion were detected in the co-culture supernatant of CAR-T cells and SMMC7721, comparable to the level of exogenous EGFRvIII-expressing U87 cells. The killing activity and cytokine secretion were both dependent on the expression level of EGFRvIII in target cells. In HCC xenograft models, CAR-T cells could effectively suppress the growth of SMMC7721. In conclusion, EGFRvIII CAR-T cells demonstrated specific antitumor effect against SMMC7721 in vitro and in vivo, providing basis for immunotherapy of HCC in future clinical use.

5.
Zhongguo Yi Liao Qi Xie Za Zhi ; 44(3): 253-257, 2020 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-32621436

RESUMO

The standard terms of infant incubators with high clinical risk and high incidence of adverse events has been tested through the introduction of YY/T 0841-2011 standard, an on-site inspection scheme for using infant incubators has been proposed, the problems existing in the inspection are analyzed and reasonable suggestions are put forward, this paper provides a certain technical reference for the whole life cycle management of the infant incubator.


Assuntos
Incubadoras para Lactentes , Exame Físico , Humanos , Lactente
6.
Cell Cycle ; 19(16): 2074-2080, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32658594

RESUMO

Neurogenic bladder (NB) is a type of double renal dysfunction caused by nerve lesions. The interstitial cells of Cajal (ICC) damage are involved in bladder dysfunction. The aim of this study is to investigate the effect of stem cell factor (SCF)/c-kit signaling pathway on ICC damage in NB model rats. Maximum cystometric capacity (MCC), bladder leak point pressures (BLPP), and bladder compliance (BC) were measured in sham-operated and NB model rats. Immunofluorescent staining for c-kit was performed to determine ICC count in rat bladder trigone. The morphology and ultrastructure changes of ICCs were observed under an electron microscope. The mRNA levels of c-kit and SCF in bladder tissues were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The protein levels of c-kit, SCF, p-JAK, p-STAT1, and p-STAT3 in bladder tissues were determined by western blot. ICC proliferation was detected by CCK-8 assay. NB resulted in changes in ultrastructure changes of ICCs and a decrease in the number of ICCs and in expression of c-kit, SCF, p-JAK, p-STAT1, and p-STAT3 in NB tissues. Inhibition of SCF/c-kit signaling pathway suppressed ICC proliferation by inhibiting JAK/STAT3 pathway. Moreover, inhibition of SCF/c-kit signaling pathway impaired the SCF-induced attenuation of ICC damage in NB model rats. Collectively, our data indicate that SCF/c-kit signaling pathway participates in ICC damage in NB.

7.
J Physiol Biochem ; 76(3): 483, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32562166

RESUMO

The above article was published online first with the following errors which have now been corrected.

8.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 38(3): 324-329, 2020 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-32573143

RESUMO

Lysophosphatidic acid (LPA) is a small phospholipid that is present in all eukaryotic tissues and blood plasma. As an extracellular signaling molecule, LPA mediates many cellular functions by binding to six known G protein-coupled receptors and activating their downstream signaling pathways. These functions indicate that LPA may play important roles in many biological processes that include organismal development, wound healing, and carcinogenesis. Recently, many studies have found that LPA has various biological effects in different kinds of bone cells. These findings suggest that LPA is a potent regulator of bone development and remodeling and holds promising application potential in bone tissue engineering. Here, we review the recent progress on the biological regulatory function of LPA in bone tissue cells.


Assuntos
Fenômenos Biológicos , Receptores de Ácidos Lisofosfatídicos , Osso e Ossos , Lisofosfolipídeos
9.
Nat Commun ; 11(1): 3207, 2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32587309

RESUMO

Real-time sensing of nitric oxide (NO) in physiological environments is critically important in monitoring neurotransmission, inflammatory responses, cardiovascular systems, etc. Conventional approaches for NO detection relying on indirect colorimetric measurement or built with rigid and permanent materials cannot provide continuous monitoring and/or require additional surgical retrieval of the implants, which comes with increased risks and hospital cost. Herein, we report a flexible, biologically degradable and wirelessly operated electrochemical sensor for real-time NO detection with a low detection limit (3.97 nmol), a wide sensing range (0.01-100 µM), and desirable anti-interference characteristics. The device successfully captures NO evolution in cultured cells and organs, with results comparable to those obtained from the standard Griess assay. Incorporated with a wireless circuit, the sensor platform achieves continuous sensing of NO levels in living mammals for several days. The work may provide essential diagnostic and therapeutic information for health assessment, treatment optimization and postsurgical monitoring.

10.
Int J Neural Syst ; 30(6): 2050032, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32498641

RESUMO

In the context of neuro-pathological disorders, neuroimaging has been widely accepted as a clinical tool for diagnosing patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). The advanced deep learning method, a novel brain imaging technique, was applied in this study to evaluate its contribution to improving the diagnostic accuracy of AD. Three-dimensional convolutional neural networks (3D-CNNs) were applied with magnetic resonance imaging (MRI) to execute binary and ternary disease classification models. The dataset from the Alzheimer's disease neuroimaging initiative (ADNI) was used to compare the deep learning performances across 3D-CNN, 3D-CNN-support vector machine (SVM) and two-dimensional (2D)-CNN models. The outcomes of accuracy with ternary classification for 2D-CNN, 3D-CNN and 3D-CNN-SVM were [Formula: see text]%, [Formula: see text]% and [Formula: see text]% respectively. The 3D-CNN-SVM yielded a ternary classification accuracy of 93.71%, 96.82% and 96.73% for NC, MCI and AD diagnoses, respectively. Furthermore, 3D-CNN-SVM showed the best performance for binary classification. Our study indicated that 'NC versus MCI' showed accuracy, sensitivity and specificity of 98.90%, 98.90% and 98.80%; 'NC versus AD' showed accuracy, sensitivity and specificity of 99.10%, 99.80% and 98.40%; and 'MCI versus AD' showed accuracy, sensitivity and specificity of 89.40%, 86.70% and 84.00%, respectively. This study clearly demonstrates that 3D-CNN-SVM yields better performance with MRI compared to currently utilized deep learning methods. In addition, 3D-CNN-SVM proved to be efficient without having to manually perform any prior feature extraction and is totally independent of the variability of imaging protocols and scanners. This suggests that it can potentially be exploited by untrained operators and extended to virtual patient imaging data. Furthermore, owing to the safety, noninvasiveness and nonirradiative properties of the MRI modality, 3D-CNN-SMV may serve as an effective screening option for AD in the general population. This study holds value in distinguishing AD and MCI subjects from normal controls and to improve value-based care of patients in clinical practice.

11.
Parasitol Res ; 119(6): 1873-1878, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32377907

RESUMO

Enterocytozoon bieneusi is a common microsporidian species, which can infect humans and various species of animals. However, little is known about E. bieneusi prevalence and genotypes in farmed raccoon dogs (Nyctereutes procyonoides) in Shandong Province, China. In this study, a total of 356 fecal samples were collected from farmed raccoon dogs in Weihai, Weifang, and Yantai cities in Shandong Province, China. A total of 23 (6.5%) samples were E. bieneusi-positive by nested PCR amplification of the internal transcribed spacer (ITS) region of ribosomal DNA. Statistical analysis showed that E. bieneusi prevalence in male raccoon dogs was higher than that in female raccoon dogs, and the highest E. bieneusi prevalence was detected in adult raccoon dogs. Sequence analysis revealed four known E. bieneusi genotypes (D, type IV, CHG1, and Peru8), and type IV (11/23) was the predominant genotype. The genotypes type IV, Peru8, and CHG1 were reported in raccoon dogs for the first time in China. Phylogenetic analysis showed that three human-pathogenic genotypes (D, type IV, and Peru8) were clustered into group 1, and the CHG1 belonged to group 2. These findings expand the current understanding of E. bieneusi prevalence and genotype distribution in raccoon dogs in China. Our study also shows that raccoon dogs are hosts for E. bieneusi belonging to several genotypes, including zoonotic ones, highlighting the possibility of transmission of this pathogen between raccoon dogs and humans.


Assuntos
Enterocytozoon , Microsporidiose/veterinária , Cães Guaxinins/parasitologia , Animais , China/epidemiologia , Enterocytozoon/genética , Fazendas , Fezes/parasitologia , Feminino , Genótipo , Masculino , Microsporidiose/epidemiologia , Microsporidiose/parasitologia , Filogenia , Reação em Cadeia da Polimerase , Prevalência
12.
Mol Med Rep ; 22(1): 67-76, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32377748

RESUMO

Renal cell carcinoma has the highest incidence rate of cancer types in the urinary system. Moreover, microRNAs (miRNA) have been closely associated with numerous types of tumor. The present study aimed to investigate the effects of miRNA (miR)­133b on the proliferation, invasion and chemosensitivity of renal cell carcinoma cells, and to determine whether its mechanism was regulated by the ERK signaling pathway. Both renal cell carcinoma and adjacent healthy tissues from 60 patients, in addition to renal cell carcinoma lines, ACHN, Caki­1, A­498 and 786­O, and 293 cells, were used in this study. miR­133b expression was measured from renal cell carcinoma, adjacent healthy tissues and renal cell carcinoma cell lines by reverse transcription­quantitative PCR. Cells were transfected with miR­133b mimic to achieve miR­133b overexpression. The proliferative, migratory and invasive ability of the cells were evaluated using MTT, wound healing and Matrigel assays, respectively, and flow cytometry was used to detect the apoptotic rate. Following treatment with an ERK inhibitor, U0126, and activator, LM22B­10, western blotting was used to detect the expression of related proteins and the activity of the ERK signaling pathway. The overexpression of miR­133b significantly inhibited cell proliferation, migration and invasion, whilst inducing apoptosis and increasing the drug sensitivity of renal cell carcinoma cells to cisplatin, docetaxel and doxorubicin. The miR­133b mimic also increased the protein expression levels of Bax and decreased the expression levels of matrix metalloproteinase (MMP)­2, MMP­9, ATP­binding cassette subfamily G2, P­glycoprotein, Bcl­2 and proliferating cell nuclear antigen, as well as the phosphorylation of ERK (P<0.05). The administration of the U0216 inhibitor demonstrated similar effects to miR­133b overexpression, and there was no significant difference compared with the miR­133b mimic transfection (P>0.05). However, the overexpression of miR­133b combined with LM22B­10 treatment weakened the anticancer effects of miR­133b mimic transfection (P<0.05). In conclusion, miR­133b overexpression was observed to inhibit the proliferation, migration and invasion of renal cell carcinoma cells and improve chemotherapeutic sensitivity; it was suggested that the mechanism maybe related to the inhibition of ERK1/2 phosphorylation and thus decreased ERK signaling pathway activity.

13.
FEBS Open Bio ; 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32416035

RESUMO

Myocarditis is an inflammatory disease of the myocardium that is associated with immune dysfunction. Earlier studies have suggested that T helper 1/2 cell imbalance plays an important role in the development of myocarditis, but the role of T follicular helper (Tfh) cells in the development of autoimmune myocarditis has not previously been reported. Here, we investigated this involvement by using a rat model of experimental autoimmune myocarditis (EAM). Inflammatory cell infiltration, myocardial structure destruction and tissue necrosis were observed in EAM myocardial tissues, and the percentages of CD4+ CXCR5+ Tfh cells and CD19+ B cells were both significantly higher in spleen and myocardial tissues of the EAM model as compared with the control group. Furthermore, the expression levels of interleukin-21, CXCL13 and myosin antibody were significantly higher in the serum of rats with EAM compared with the control group on days 14 and 35 after immunization. Fourteen or 35 days after immunization, the expression levels of interleukin-21 and CXCL13 were both significantly higher in myocardial tissues of rats with EAM as compared with the control group. Our findings suggest that Tfh cell balance is disrupted during the pathological process of autoimmune myocarditis.

14.
J Physiol Biochem ; 76(3): 373-382, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32424454

RESUMO

The epithelial-to-mesenchymal transition (EMT)-based tubulointerstitial fibrosis is the major pathological feature of diabetic kidney disease (DKD). While several studies have linked cell cycle dysregulation to various kidney injuries in recent years, its involvement in fibrosis of DKD is far from being clarified. ING2 (inhibitor of growth 2) is the second member of the inhibitor of growth family and participates in the regulation of many cellular processes. So far the role of ING2 in DKD remains largely unknown. In the present study, ING2 expression was detected by western blotting and immunofluorescent staining both in vitro high glucose-stimulated human proximal tubular epithelial cells (HK-2) and in vivo streptozotocin-induced diabetic mice. Cell proliferation was analyzed by CCK-8 and EdU assay, and cell cycle arrest was measured by flow cytometry. Quantitative polymerase chain reaction (qPCR) and western blotting were used to detect the EMT markers, and the p53 signaling activation was evaluated by chromatin immunoprecipitation (ChIP), qPCR, and western blotting. We found that the proliferation of the cells was reduced upon high glucose stimulation, which was accompanied by cell cycle arrest. The expression of ING2 was increased in hyperglycemia conditions both in vivo and in vitro. ING2 suppression ameliorated the reduced proliferation and cell cycle arrest induced by high glucose in HK-2 cells. Moreover, ING2 knockdown suppressed p21 expression by reducing p53 acetylation and finally alleviated the EMT progress in the high glucose-stimulated HK-2 cells. Our study demonstrated that cell cycle regulation is bound up with the kidney fibrosis in DKD, suggesting a novel function of ING2 as a potential therapeutic strategy targeting cell cycle arrest for DKD.

15.
ACS Appl Mater Interfaces ; 12(23): 25572-25580, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32412741

RESUMO

Reactive oxygen species-mediated tumor chemodynamic therapy and photodynamic therapy have captured extensive attention in practical cancer combination therapies. However, the severe treatment conditions and the hypoxic microenvironment of solid tumors significantly limit the efficacy of these therapies. This work demonstrates the design and fabrication of a multifunctional persistent luminescence nanoplatform (PHFI, refers to PLNP-HSA-Fe3+-IR780) for cancer multimodal imaging and effective photoenhanced combination therapy. The near-infrared-emitted persistent luminescence nanoparticles (PLNP) was modified with human serum albumin (HSA) combined with an IR780 probe and Fe3+. The synthesized PHFI possesses high longitudinal relaxivity, obvious photoacoustic contrast signals, and long-lasting persistent luminescence, indicating that PHFI can be used for cancer magnetic resonance imaging, photoacoustic imaging, and persistent luminescence multimodal imaging. PHFI shows intrinsic photoenhanced Fenton-like catalytic activities as well as photodynamic and photothermal effects and thereby can effectively overcome severe treatment conditions for killing tumor cells. It is worth noting that PHFI serving as a rechargeable internal light source for photoenhanced combination therapy was first disclosed. We believe that our work shows the great potential of PHFI for cancer theranostics and will advance the development of PLNP-based nanoplatforms in tumor catalytic therapy.

16.
Korean J Parasitol ; 58(2): 181-184, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32418387

RESUMO

Blastocystis, an enteric protist, has been reported to be an important cause of protozoal gastrointestinal manifestations in humans and animals worldwide. Animals harboring certain Blastocystis subtypes (STs) may serve as a potential source of human infection. However, information about the prevalence and genetic diversity of Blastocystis in alpacas is limited. In the present study, a total of 366 fecal samples from alpacas in Shanxi Province, northern China, were examined for Blastocystis by PCR amplification of the small subunit rRNA gene, followed by sequencing and phylogenetic analysis. The prevalence of Blastocystis in alpacas was 23.8%, and gender difference in the prevalence of Blastocystiswas observed. The most predominant Blastocystis ST was ST10, followed by ST14 and ST5. The detection of ST5, a potentially zoonotic genotype, indicates that alpacas harboring ST5 could be a potential source of human infection with Blastocystis. These data provide new insight into the prevalence and genetic diversity of Blastocystis in alpacas.

17.
J Am Coll Cardiol ; 75(19): 2387-2399, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32408975

RESUMO

BACKGROUND: Large blood pressure (BP) variability may contribute to stroke and dementia, but the mechanisms are largely unknown. OBJECTIVES: This study investigated the association of BP variation, considering its magnitude and direction, with the presence and progression of subclinical brain disease in the general population. METHODS: This study included 2,348 participants age ≥55 years from a prospective cohort study. BP was measured at each visit every 3 to 4 years from 1990 onward. Brain magnetic resonance imaging (MRI) was performed at all visits from 2005 onward. The authors primarily assessed variation as the absolute difference in BP divided by the mean over 2 sequential visits for both systolic BP (SBP) and diastolic BP (DBP), and further assessed the direction of the variation. The authors investigated the multivariate-adjusted associations of BP variation with subsequent measurements of MRI markers of cerebral small vessel disease, brain tissue volumes, and white matter microstructural integrity. Longitudinal changes in these markers also were assessed. RESULTS: A large SBP variation (top vs. bottom tertiles), measured on average 7 years preceding brain MRI, was associated with higher odds of having severe white matter hyperintensities (WMH) (odds ratio [OR]: 1.32; 95% confidence interval [CI]: 1.21 to 1.43), lacunes (OR: 1.25; 95% CI: 1.04 to 1.48), and microbleeds (OR: 1.16; 95% CI: 1.03 to 1.31). Similarly, this variation was associated with smaller total brain volume and worse white matter microstructural integrity (all p < 0.001). A large SBP variation was also associated with the progression of WMH (rate ratio [RR]: 1.14; 95% CI: 1.02 to 1.27). Higher burdens of these brain imaging markers were observed with both large rises and falls in SBP. Similar findings were observed for DBP variation. CONCLUSIONS: Elevated BP variation was associated with a wide range of subclinical brain structural changes, including MRI markers of cerebral small vessel disease, smaller brain tissue volumes, and worse white matter microstructural integrity. These subclinical brain changes could be the underlying mechanisms linking BP variation to dementia and stroke.

18.
Neural Regen Res ; 15(10): 1962-1968, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32246647

RESUMO

Long noncoding RNA (lncRNA) regulates the proliferation and migration of human retinal endothelial cells, as well as retinal neovascularization in diabetic retinopathy. Based on similarities between the pathogenesis of retinopathy of prematurity (ROP) and diabetic retinopathy, lncRNA may also play a role in ROP. Seven-day-old mice were administered 75 ± 2% oxygen for 5 days and normoxic air for another 5 days to establish a ROP model. Expression of lncRNA and mRNA in the retinal tissue of mice was detected by high-throughput sequencing technology, and biological functions of the resulted differentially expressed RNAs were evaluated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. The results showed that compared with the control group, 57 lncRNAs were differentially expressed, including 43 upregulated and 14 downregulated, in the retinal tissue of ROP mice. Compared with control mice, 42 mRNAs were differentially expressed in the retinal tissue of ROP mice, including 24 upregulated and 18 downregulated mRNAs. Differentially expressed genes were involved in ocular development and related metabolic pathways. The differentially expressed lncRNAs may regulate ROP in mice via microRNAs and multiple signaling pathways. Our results revealed that these differentially expressed lncRNAs may be therapeutic targets for ROP treatment. This study was approved by the Medical Ethics Committee of Shengjing Hospital of China Medical University on February 25, 2016 (approval No. 2016PS074K).

19.
Cell Mol Neurobiol ; 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32239388

RESUMO

Spinal cord injury (SCI) is a grievous neurology-related disorder that causes many devastating symptoms. Emerging roles of long non-coding RNAs (lncRNA) have been shown to play critical roles in multiple neurological diseases. This research planned to dig the function and latent molecular mechanisms of the lncRNA CCAT1 on OGD/R-disposed injury in astrocytes. We observed that CCAT1 expression was diminished and miR-218 expression was elevated in astrocytes during OGD/R. Additionally, an abundance of CCAT1 obviously amplified cell viability and restrained OGD/R-triggered apoptosis in astrocytes, as characterized by reduced levels of pro-apoptotic proteins Bax and C-caspase-3, concomitant with elevated level of anti-apoptotic Bcl-2 protein. Furthermore, administration of CCAT1 remarkably mitigated OGD/R injury-induced neuro-inflammatory responses, reflected in a reduction of inflammatory cytokines including TNF-α, IL-1ß, and IL-6. In action, CCAT1 served as an endogenous sponge effectively downregulating miR-218 expression by binding directly to it, and a negative regulatory relationship between miR-218 and NFAT5. Mechanistically, introduction of miR-218 reversed the inhibitory effects of CCAT1 on OGD/R-induced apoptosis and inflammation damage, which directly resulted from the inhibition of miR-218 and its targeting of NFAT5. Collectively, our study illuminated a new CCAT1/miR-218/NFAT5 regulatory axis in which CCAT1 served as a competing endogenous RNA by sponging miR-218, effectively upregulating NFAT5 expression, thereby alleviating apoptosis and inflammation damage under OGD/R condition. CCAT1 is, therefore, a putative therapeutic target for SCI, based on the results of this study and the potential application of CCAT1 as a neuroprotective agent.

20.
Transl Stroke Res ; 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32240524

RESUMO

Regulatory T cells (Tregs) play an immunosuppressive role in various diseases, yet their function remains controversial in stroke and obscure in diabetic stroke. In the present study, Tregs were found downregulated in the peripheral blood of type 2 diabetes mellitus (T2DM) stroke models and patients compared with controls. In ischemic stroke mice (both T2DM and wild type), endogenous Tregs boosted by CD28SA increased CD206+ M2 macrophage/microglia cells, decreased infarct volumes, and improved neurological recovery. Our results demonstrated the potential of boosting Tregs for treating T2DM stroke. Furthermore, we utilized an optical imaging probe (IRD-αCD206) to target M2 macrophage/microglia cells and demonstrated its effect in visualizing M2 macrophage/microglia cells in vivo in ischemic brain tissue.

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