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1.
J Neurosci Res ; 102(1): e25254, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37814994

ABSTRACT

Ivermectin (IVM), a semi-synthetic macrolide parasiticide, has demonstrated considerable effectiveness in combating internal and external parasites, particularly nematodes and arthropods. Its remarkable ability to control parasites has earned it significant recognition, culminating in Satoshi Omura and William C. Campbell's receipt of the 2015 Nobel Prize in Physiology or Medicine for their contributions to the development of IVM. In recent years, investigations have revealed that IVM possesses antitumor properties. It can suppress the growth of various cancer cells, including glioma, through a multitude of mechanisms such as selective targeting of tumor-specific proteins, inducing programmed cell death, and modulation of tumor-related signaling pathways. Hence, IVM holds tremendous potential as a novel anticancer drug. This review seeks to provide an overview of the underlying mechanisms that enable IVM's capacity to suppress glioma. Furthermore, it aims to elucidate the challenges and prospects associated with utilizing IVM as a new anticancer agent.


Subject(s)
Antineoplastic Agents , Glioma , Humans , Ivermectin/pharmacology , Ivermectin/therapeutic use , Ivermectin/history , Glioma/drug therapy , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Nobel Prize , Apoptosis
2.
Adv Healthc Mater ; 12(24): e2300711, 2023 09.
Article in English | MEDLINE | ID: mdl-37166979

ABSTRACT

Tumor cells resist oxidative damage and apoptosis by activating defense mechanisms. Herein, a self-delivery biomedicine (designated as BSC) is developed by the self-assembly of Bortezomib (BTZ), Sabutoclax (Sab) and Chlorin e6 (Ce6). Interestingly, BTZ can be coordinated with Sab to promote the assembly of uniform ternary biomedicine through non-covalent intermolecular interactions. Moreover, BTZ as a proteasome inhibitor can prevent tumor cells from scavenging damaged proteins to reduce their oxidative resistance. Sab can downregulate B-cell lymphoma 2 (Bcl-2) to decrease the antiapoptotic protein. Both the proteasome and Bcl-2 inhibitions contribute to increasing cell apoptosis and amplifying photodynamic therapy (PDT) efficacy of Ce6. Encouragingly, carrier-free BSC receives all biological activities of these assembly elements, including photodynamic performance as well as inhibitory capabilities of proteasome and Bcl-2. Besides, BSC has a preferable cellular uptake ability and tumor retention property, which increase the drug delivery efficiency and bioavailability. In vitro and in vivo research demonstrate the superior PDT efficiency of BSC by proteasome and Bcl-2 inhibitions. Of special note, the coordination-driven self-assembly of BSC is pH-responsive, which can be disassembled for controlled drug release upon tumor acidic microenvironment. This study will expand the applicability of self-delivery nanomedicine with sophisticated mechanisms for tumor treatment.


Subject(s)
Nanoparticles , Photochemotherapy , Porphyrins , Photosensitizing Agents/pharmacology , Proteasome Endopeptidase Complex , Cell Line, Tumor , Porphyrins/pharmacology
3.
Mol Ther Nucleic Acids ; 31: 763-778, 2023 Mar 14.
Article in English | MEDLINE | ID: mdl-36937621

ABSTRACT

Inherited and age-related retinal degenerations are the commonest causes of blindness without effective treatments. Retinal progenitor cells (RPCs), which have the multipotency to differentiate into various retinal cell types, are regarded as a promising source of cell transplantation therapy for retinal degenerative diseases. However, the self-limited expansion of RPCs causes difficulty in cell source supply and restrict its clinical treatment. In this work, we found that inhibition of microRNA-449a (miR-449a) in RPCs can promote proliferation and inhibit apoptosis of RPCs, partially through upregulating Notch signaling. Further optimization of transduction miR-449a inhibitor into RPCs by endothelial cell-derived exosomes can promote the survival of RPCs transplanted in vivo and reduce cell apoptosis in retinal degeneration mouse models. In summary, these studies have shown that exosome-miR-449a inhibitor can effectively promote the expansion of RPCs in vitro and enhance transplanted RPCs survival in vivo, which might provide a novel intervention strategy for retinal degenerations in the future.

4.
Brain Sci ; 13(2)2023 Jan 28.
Article in English | MEDLINE | ID: mdl-36831764

ABSTRACT

Motor imagery brain-computer interface (MI-based BCIs) have demonstrated great potential in various applications. However, to well generalize classifiers to new subjects, a time-consuming calibration process is necessary due to high inter-subject variabilities of EEG signals. This process is costly and tedious, hindering the further expansion of MI-based BCIs outside of the laboratory. To reduce the calibration time of MI-based BCIs, we propose a novel domain adaptation framework that adapts multiple source subjects' labeled data to the unseen trials of target subjects. Firstly, we train one Subject Separation Network(SSN) for each of the source subjects in the dataset. Based on adversarial domain adaptation, a shared encoder is constructed to learn similar representations for both domains. Secondly, to model the factors that cause subject variabilities and eliminate the correlated noise existing in common feature space, private feature spaces orthogonal to the shared counterpart are learned for each subject. We use a shared decoder to validate that the model is actually learning from task-relevant neurophysiological information. At last, an ensemble classifier is built by the integration of the SSNs using the information extracted from each subject's task-relevant characteristics. To quantify the efficacy of the framework, we analyze the accuracy-calibration cost trade-off in MI-based BCIs, and theoretically guarantee a generalization bound on the target error. Visualizations of the transformed features illustrate the effectiveness of domain adaptation. The experimental results on the BCI Competition IV-IIa dataset prove the effectiveness of the proposed framework compared with multiple classification methods. We infer from our results that users could learn to control MI-based BCIs without a heavy calibration process. Our study further shows how to design and train Neural Networks to decode task-related information from different subjects and highlights the potential of deep learning methods for inter-subject EEG decoding.

5.
World Neurosurg ; 172: e1-e11, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36167302

ABSTRACT

BACKGROUND: The pineal tumor was once considered as a restricted area for surgery. Such cases are rare, with many different opinions on surgical treatment. This study aimed to review our experience of tumor treatment in the pineal region and explore the optimal treatment strategy. METHODS: The clinical data of 72 patients with pineal tumors from January 1997 to May 2015 (18 years) were retrospectively analyzed. Preoperative preparation, pathology type, tumor resection rate, surgical approach, and follow-up outcomes were used as the indicators to evaluate the treatment efficacy. RESULTS: The Krause approach was used in 46 cases, the Poppen approach in 10 cases, and the transcallosal-lateral ventricle-choroid fissure approach in 16 cases. The postoperative pathological results were as follows: 24 cases of germinoma, 11 of teratoma, 15 of glioma, 6 of meningioma, 11 of Pineocytoma, 2 of cholesteatoma, 2 of cavernous hemangioma, and 1 of choriocarcinoma. Further, the study included 64 cases of total surgical resections, 8 of subtotal resections, and 2 deaths. The follow-up period was from 7 months to 10 years. Further, 51 (70.8%) patients were followed up. The multivariate regression model showed that the surgical method and the pathological type contributed significantly to predicting outcomes. CONCLUSIONS: The type of pathology, extent of excision, and surgical approach had a significant impact on the prognosis of patients. The transcallosal-lateral ventricle-choroid fissure approach for large and medium-sized pineal tumors near the posterior part of the third ventricle had good efficacy.


Subject(s)
Brain Neoplasms , Meningeal Neoplasms , Pineal Gland , Pinealoma , Humans , Pinealoma/surgery , Pinealoma/pathology , Retrospective Studies , Pineal Gland/surgery , Pineal Gland/pathology , Brain Neoplasms/surgery , Brain Neoplasms/pathology , Meningeal Neoplasms/pathology
6.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-985479

ABSTRACT

Perfluorinated compounds, especially Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), are widely detected in water environments in China. Considering the potential health risks of drinking water exposure routes, PFOA and PFOS have been added to the water quality reference index of the newly issued "Standards for Drinking Water Quality (GB5749-2022)", with limit values of 40 and 80 ng/L, respectively. This study analyzed and discussed the relevant technical contents for determining the limits of the hygiene standard, including the environmental existence level and exposure status of PFOA and PFOS, health effects, derivation of safety reference values, and determination of hygiene standard limits. It also proposed prospects for the future direction of formulating drinking water standards.


Subject(s)
Humans , Water Quality , Drinking Water , Fluorocarbons/analysis , Caprylates/analysis , China , Water Pollutants, Chemical/analysis
7.
China Tropical Medicine ; (12): 619-2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-979776

ABSTRACT

@#Abstract: Objective To investigate the molecular characteristics and drug resistance of non-O1/non-O139 Vibrio cholerae in Zhongshan City, and to provide laboratory basis for cholera prevention and control. Methods The strains of non-O1/non-O139 Vibrio cholerae isolated from sporadic patients and aquatic products from 2015 to 2021 in Zhongshan city were collected. The identification and cluster analysis of the strains were analyzed by matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS), the ctxA virulence gene of strains were detected by real-time fluorescence quantitative PCR, the cluster analysis of the strains was analyzed by pulsed-field gel electrophoresis (PFGE), and the drug resistance of the strains were analyzed by microbroth dilution method. Results From 2015 to 2021, 33 strains of non-O1/non-O139 Vibrio cholerae were isolated from Zhongshan City, including 28 strains from sporadic patients and 5 strains from aquatic products. Through MALDI-TOF-MS identification, 33 strains of non-O1/non-O139 Vibrio cholera can be identified to the level of species, and the identification results were all Vibrio cholerae. Among 33 non-O1/non-O139 Vibrio cholerae strains, 1 strain carried the ctxA virulence gene. The drug-resistant strains accounted for 69.7% (23/33), and the multidrug resistant strains accounted for 18.2% (6/33). A total of 7 kinds of drug resistance spectrum were produced, including 3 kinds of multidrug resistant spectrum, and showed drug resistance to 8 antibiotics, among which the resistance rates to streptomycin, cefazolin and compound sulfamethoxazole were above 30%. The 33 strains of non-O1/non-O139 Vibrio cholerae were divided into 32 PFGE fingerprints with a similarity ranging from 61.7% to 100%. MALDI-TOF-MS cluster analysis divided 33 non-O1/non-O139 Vibrio cholerae strains into two clusters. Conclusions The results of molecular typing of non-O1/non-O139 Vibrio cholerae in Zhongshan City presented diversity, and no significant correlation was found between PFGE and MALDI-TOF-MS cluster analysis. The strains demonstrated various degrees of resistance to certain antibiotics, and there were multidrug-resistant and toxigenic strains. Therefore, it is necessary to alert to the harmfulness of non-O1/non-O139 Vibrio cholerae and enhance monitoring.

8.
Brain Sci ; 12(9)2022 Sep 11.
Article in English | MEDLINE | ID: mdl-36138967

ABSTRACT

Virtual reality (VR) technology provides highly immersive depth perception experiences; nevertheless, stereoscopic visual fatigue (SVF) has become an important factor currently hindering the development of VR applications. However, there is scant research on the underlying neural mechanism of SVF, especially those induced by VR displays, which need further research. In this paper, a Go/NoGo paradigm based on disparity variations is proposed to induce SVF associated with depth perception, and the underlying neural mechanism of SVF in a VR environment was investigated. The effects of disparity variations as well as SVF on the temporal characteristics of visual evoked potentials (VEPs) were explored. Point-by-point permutation statistical with repeated measures ANOVA results revealed that the amplitudes and latencies of the posterior VEP component P2 were modulated by disparities, and posterior P2 amplitudes were modulated differently by SVF in different depth perception situations. Cortical source localization analysis was performed to explore the original cortex areas related to certain fatigue levels and disparities, and the results showed that posterior P2 generated from the precuneus could represent depth perception in binocular vision, and therefore could be performed to distinguish SVF induced by disparity variations. Our findings could help to extend an understanding of the neural mechanisms underlying depth perception and SVF as well as providing beneficial information for improving the visual experience in VR applications.

9.
IEEE J Biomed Health Inform ; 26(7): 2963-2973, 2022 07.
Article in English | MEDLINE | ID: mdl-35316199

ABSTRACT

Stereoscopic visual fatigue (SVF) due to prolonged immersion in the virtual environment can lead to negative user experience, thus hindering the development of virtual reality (VR) industry. Previous studies have focused on investigating the evaluation indicators associated with SVF, while few studies have been conducted to reveal the underlying neural mechanism, especially in VR applications. In this paper, a modified Go/NoGo paradigm was adopted to induce SVF in VR environment with Go trials for maintaining participants' attention and NoGo trials for investigating the neural effects under SVF. Random dot stereograms (RDSs) with 11 disparities were presented to evoke the depth-related visual evoked potentials (DVEPs) during 64-channel EEG recordings. EEG datasets collected from 15 participants in NoGo trials were selected to conduct individual processing and group analysis, in which the characteristics of the DVEPs components for various fatigue degrees were compared and independent components were clustered to explore the original cortex areas related to SVF. Point-by-point permutation statistics revealed that DVEPs sample points from 230 ms to 280 ms (component P2) in most brain areas changed significantly when SVF increased. Additionally, independent component analysis (ICA) identified that component P2 which originated from posterior cingulate cortex and precuneus, was associated statistically with SVF. We believe that SVF is rather a conscious status concerning the changes of self-awareness or self-location awareness than the performance reduction of retinal image processing. Moreover, we suggest that indicators representing higher conscious state may be a better indicator for SVF evaluation in VR environments.


Subject(s)
Asthenopia , Cerebral Cortex , Evoked Potentials, Visual , Asthenopia/physiopathology , Attention/physiology , Humans , Virtual Reality
10.
Theranostics ; 12(4): 1816-1828, 2022.
Article in English | MEDLINE | ID: mdl-35198075

ABSTRACT

Rationale: Macrophages play multi-dimensional roles in hepatic fibrosis. Studies have implicated Notch signaling mediated by the transcription factor RBP-J in macrophage activation and plasticity. Additionally, we have previously shown that myeloid-specific disruption of RBP-J can ameliorate hepatic fibrosis in mice. Accordingly, we next asked whether blocking Notch signaling in macrophages could serve as a therapeutic strategy to treat hepatic fibrosis. In this study, we used a combination of transcription factor decoy oligodeoxynucleotides (ODNs) and exosomes to test this possibility. Methods: Hairpin-type decoy oligodeoxynucleotides (ODNs) were designed for the transcription factor RBP-J. The effects of RBP-J decoy ODNs on Notch signaling were evaluated by western blot, quantitative RT-PCR, luciferase reporter assays, and electrophoretic mobility shift assays. ODNs were loaded into HEK293T-derived exosomes by electroporation. A hepatic fibrosis mouse model was established by the intraperitoneal injection of carbon tetrachloride or bile duct ligation. Mice with hepatic fibrosis were administered exosomes loaded with RBP-J decoy ODNs via tail vein injection. The in vivo distribution of exosomes was analyzed by fluorescence labeling and imaging. Liver histology was examined using hematoxylin and eosin, Sirius red, and Masson staining, as well as immunohistochemical staining for Col1α1 and αSMA. Results: We found that RBP-J decoy ODNs could be efficiently loaded into exosomes and inhibit the activation of Notch signaling. Furthermore, exosomes administered via the tail vein were found to be primarily taken up by hepatic macrophages in mice with liver fibrosis. Importantly, RBP-J decoy ODNs delivered by exosomes could efficiently inhibit Notch signaling in macrophages and ameliorate hepatic fibrosis in mice. Conclusions: Combined, our data showed that the infusion of exosomes loaded with RBP-J decoy ODNs represents a promising therapeutic strategy for the treatment of hepatic fibrosis.


Subject(s)
Exosomes , Oligodeoxyribonucleotides , Animals , HEK293 Cells , Humans , Liver Cirrhosis , Mice , Oligodeoxyribonucleotides/pharmacology , Signal Transduction
11.
Acta Pharmacol Sin ; 43(3): 703-711, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34017066

ABSTRACT

Targeting autophagy might be a promising anticancer strategy; however, the dual roles of autophagy in cancer development and malignancy remain unclear. NSCLC (non-small cell lung cancer) cells harbour high levels of SQSTM1 (sequestosome 1), the autophagy receptor that is critical for the dual roles of autophagy. Therefore, mechanistic insights into SQSTM1 modulation may point towards better approaches to treat NSCLC. Herein, we used multiple autophagy flux models and autophagy readouts to show that aldo-keto reductase family 1 member C1 (AKR1C1), which is highly expressed in NSCLC, promotes autophagy by directly binding to SQSTM1 in a catalytic-independent manner. This interaction may be strengthened by reactive oxygen species (ROS), important autophagy inducers. Further mechanistic research demonstrated that AKR1C1 interacts with SQSTM1 to augment SQSTM1 oligomerization, contributing to the SQSTM1 affinity for binding cargo. Collectively, our data reveal a catalytic-independent role of AKR1C1 for interacting with SQSTM1 and promoting autophagy. All these findings not only reveal a novel functional role of AKR1C1 in the autophagy process but also indicate that modulation of the AKR1C1-SQSTM1 interaction may be a new strategy for targeting autophagy.


Subject(s)
Aldo-Keto Reductases/metabolism , Autophagy/physiology , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Oxidative Stress/physiology , Sequestosome-1 Protein/metabolism , Cell Line, Tumor , Humans
12.
Front Cell Dev Biol ; 9: 779373, 2021.
Article in English | MEDLINE | ID: mdl-34869383

ABSTRACT

The quiescence, activation, and subsequent neurogenesis of neural stem cells (NSCs) play essential roles in the physiological homeostasis and pathological repair of the central nervous system. Previous studies indicate that transmembrane protein Ttyh1 is required for the stemness of NSCs, whereas the exact functions in vivo and precise mechanisms are still waiting to be elucidated. By constructing Ttyh1-promoter driven reporter mice, we determined the specific expression of Ttyh1 in quiescent NSCs and niche astrocytes. Further evaluations on Ttyh1 knockout mice revealed that Ttyh1 ablation leads to activated neurogenesis and enhanced spatial learning and memory in adult mice (6-8 weeks). Correspondingly, Ttyh1 deficiency results in accelerated exhaustion of NSC pool and impaired neurogenesis in aged mice (12 months). By RNA-sequencing, bioinformatics and molecular biological analysis, we found that Ttyh1 is involved in the regulation of calcium signaling in NSCs, and transcription factor NFATc3 is a critical effector in quiescence versus cell cycle entry regulated by Ttyh1. Our research uncovered new endogenous mechanisms that regulate quiescence versus activation of NSCs, therefore provide novel targets for the intervention to activate quiescent NSCs to participate in injury repair during pathology and aging.

13.
Front Cell Dev Biol ; 9: 620883, 2021.
Article in English | MEDLINE | ID: mdl-33614649

ABSTRACT

Formation of glioma stem cells (GSCs) is considered as one of the main reasons of temozolomide (TMZ) resistance in glioma patients. Recent studies have shown that tumor microenvironment-derived signals could promote GSCs formation. But the critical molecule and underlying mechanism for GSCs formation after TMZ treatment is not entirely identified. Our study showed that TMZ treatment promoted GSCs formation by glioma cells; TMZ treatment of biopsy-derived glioblastoma multiforme cells upregulated HMGB1; HMGB1 altered gene expression profile of glioma cells with respect to mRNA, lncRNA and miRNA. Furthermore, our results showed that TMZ-induced HMGB1 increased the formation of GSCs and when HMGB1 was downregulated, TMZ-mediated GSCs formation was attenuated. Finally, we showed that the effect of HMGB1 on glioma cells was mediated by TLR2, which activated Wnt/ß-catenin signaling to promote GSCs. Mechanistically, we found that HMGB1 upregulated NEAT1, which was responsible for Wnt/ß-catenin activation. In conclusion, TMZ treatment upregulates HMGB1, which promotes the formation of GSCs via the TLR2/NEAT1/Wnt pathway. Blocking HMGB1-mediated GSCs formation could serve as a potential therapeutic target for preventing TMZ resistance in GBM patients.

14.
IEEE Trans Neural Syst Rehabil Eng ; 28(12): 2794-2804, 2020 12.
Article in English | MEDLINE | ID: mdl-33406041

ABSTRACT

Prolonged viewing of 3D content may result in severe fatigue symptoms, giving negative user experience thus hindering the development of 3D industry. For 3D visual fatigue evaluation, previous studies focused on exploring the changes of frequency-domain features in EEG for various fatigue degrees. However, their time-domain features were scarcely investigated. In this study, a modified paradigm with a random disparities order is adopted to evoke the depth-related visual evoked potentials (DVEPs). Then the characteristics of the DVEPs components for various fatigue degrees are compared using one-way repeated-measurement ANOVA. Point-by-point permutation statistics revealed sample points from 100ms to 170ms - including P1 and N1 - in sensors Pz and P4 changed significantly with visual fatigue. More specifically, we find that the amplitudes of P1 and N1 change significantly when visual fatigue increases. Additionally, independent component analysis identify P1 and N1 which originate from posterior cingulate cortex are associated statistically with 3D visual fatigue. Our results indicate there is a significant correlation between 3D visual fatigue and P1 amplitude, as well as N1, of DVEPs on right parietal areas. We believe the characteristics (e.g., amplitude and latency) of identified components may be the indicators of 3D visual fatigue evaluation. Furthermore, we argue that 3D visual fatigue may be associated with the activities decrease of the attention and the processing capacity of disparity.


Subject(s)
Asthenopia , Evoked Potentials, Visual , Attention , Cerebral Cortex , Electroencephalography , Humans
15.
Biochem Genet ; 58(2): 245-256, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31552564

ABSTRACT

The common variants of the methylenetetrahydrofolate reductase (MTHFR) gene are related to the activity of the MTHFR enzyme and the concentrations of blood homocysteine (Hcy). This study was designed to investigate the associations of MTHFR in Chinese populations with early-onset coronary artery disease (EOCAD). The two common variants of the MTHFR gene were genotyped in 875 EOCAD patients and 956 controls using PCR, followed by direct sequencing of the PCR product. Serum levels of Hcy were measured using an automatic biochemistry analyzer. A significant association between the MTHFR-677C/T variant and the risk of EOCAD was detected in CC versus TT (odds ratio (OR) 1.456, 95% confidence interval (CI) 1.120-1.892), dominant genetic model (OR 1.266, 95% CI 1.027-1.546), and recessive genetic model (OR 1.306, 95% CI 1.040-1.639). Hcy was most abundant in TT genotype (18.31 ± 7.22 µmol/L), least abundant in CC genotype (11.37 ± 5.23 µmol/L), and detectable at intermediate levels in heterozygotes (15.25 ± 6.58 µmol/L). Elevated serum Hcy levels were an independent risk factor for EOCAD (ORadjust 1.431, 95% CI 1.135-1.763). Our findings indicated that the T allele of -677C/T MTHFR variant predisposes to high levels of Hcy, and that the T allele is an important risk factor for EOCAD in the Chinese population.


Subject(s)
Coronary Artery Disease , Genetic Predisposition to Disease , Homocysteine/blood , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Adult , Case-Control Studies , China , Coronary Artery Disease/epidemiology , Coronary Artery Disease/genetics , Female , Humans , Male , Middle Aged , Polymorphism, Genetic , Risk Factors
17.
Ther Adv Chronic Dis ; 10: 2040622319891539, 2019.
Article in English | MEDLINE | ID: mdl-31839921

ABSTRACT

BACKGROUND: Adenosine deaminase (ADA) regulates purine metabolism through the conversion of adenosine to uric acid (UA). Adenosine and UA are closely associated with cardiovascular events, but the correlation between serum ADA activity and coronary artery disease (CAD) has not been defined. METHODS: We performed a hospital-based retrospective case-control study that included a total of 5212 patients with CAD and 4717 sex- and age-matched controls. The serum activity of ADA was determined by peroxidase assays in an automatic biochemistry analyzer. RESULTS: Serum ADA activity in the CAD group (10.08 ± 3.57 U/l) was significantly lower than that of the control group (11.71 ± 4.20 U/l, p < 0.001). After adjusting for conventional factors, serum ADA activity negatively correlated with the presence of CAD (odds ratio = 0.852, 95% confidence interval: 0.839-0.865, p < 0.001). Among the patients with CAD, serum ADA activity was lowest in patients with myocardial infarction (MI; 9.77 ± 3.80 U/l). Diabetes mellitus and hypertension increased the serum ADA activity in CAD patients. CONCLUSIONS: Serum ADA activity is significantly attenuated in patients with CAD, particularly in MI. We propose a mechanism by which the body maintains adenosine levels to protect the cardiovascular system in the event of CAD.

18.
Cell Death Dis ; 10(12): 869, 2019 11 18.
Article in English | MEDLINE | ID: mdl-31740664

ABSTRACT

Extracellular vesicles (EVs) including exosomes can serve as mediators of cell-cell communication under physiological and pathological conditions. However, cargo molecules carried by EVs to exert their functions, as well as mechanisms for their regulated release and intake, have been poorly understood. In this study, we examined the effects of endothelial cells-derived EVs on neurons suffering from oxygen-glucose deprivation (OGD), which mimics neuronal ischemia-reperfusion injury in human diseases. In a human umbilical endothelial cell (HUVEC)-neuron coculture assay, we found that HUVECs reduced apoptosis of neurons under OGD, and this effect was compromised by GW4869, a blocker of exosome release. Purified EVs could be internalized by neurons and alleviate neuronal apoptosis under OGD. A miRNA, miR-1290, was highly enriched in HUVECs-derived EVs and was responsible for EV-mediated neuronal protection under OGD. Interestingly, we found that OGD enhanced intake of EVs by neurons cultured in vitro. We examined the expression of several potential receptors for EV intake and found that caveolin-1 (Cav-1) was upregulated in OGD-treated neurons and mice suffering from middle cerebral artery occlusion (MCAO). Knock-down of Cav-1 in neurons reduced EV intake, and canceled EV-mediated neuronal protection under OGD. HUVEC-derived EVs alleviated MCAO-induced neuronal apoptosis in vivo. These findings suggested that ischemia likely upregulates Cav-1 expression in neurons to increase EV intake, which protects neurons by attenuating apoptosis via miR-1290.


Subject(s)
Caveolin 1/metabolism , Endothelial Cells/metabolism , Extracellular Vesicles/metabolism , MicroRNAs/metabolism , Neurons/metabolism , Animals , Apoptosis , Humans , Male , Mice , Mice, Inbred C57BL , Up-Regulation
19.
Biochem Biophys Res Commun ; 514(3): 842-847, 2019 06 30.
Article in English | MEDLINE | ID: mdl-31079925

ABSTRACT

Mammalian neural stem cells (NSCs) are not only responsible for normal development of the central nervous system (CNS), but also participate in brain homeostasis and repair, thus hold promising clinical potentials in the treatment of neurodegenerative diseases and trauma. However the molecular networks regulating the stemness and differentiation of NSCs have not been fully understood. In this study, we show that Tweety-homolog 1 (Ttyh1), a five-pass transmembrane protein specifically expressed in mouse brain, is involved in maintaining stemness of murine NSCs. Blocking or activating Notch signal led to downregulation and upregulation of Ttyh1 in cultured NSCs, respectively, suggesting that Ttyh1 is under the control of Notch signaling. Knockdown of Ttyh1 in cultured NSCs resulted in a transient increase in the number and size of neurospheres, followed by a decrease of stemness as manifested by compromised neurosphere formation, downregulated stem cell markers, and increased neuronal differentiation. We generated Ttyh1 knockout mice by deleting its exon 4 using the CRISPR-Cas9 technology. Surprisingly, in contrast to a previous report, Ttyh1 knockout did not result in embryonic lethality. NSCs derived from Ttyh1 knockout mice phenocopied NSCs transfected with Ttyh1 siRNA. Immunofluorescence showed that loss of Ttyh1 leads to the increase of neurogenesis in adult mice. Taken together, these findings indicate that Ttyh1, which is likely downstream to Notch signaling, plays an important role in regulating NSCs.


Subject(s)
Cell Differentiation , Membrane Proteins/deficiency , Neural Stem Cells/cytology , Neural Stem Cells/metabolism , Receptors, Notch/metabolism , Signal Transduction , Animals , Embryo Loss/pathology , Membrane Proteins/genetics , Membrane Proteins/metabolism , Mice , Mice, Knockout , Neurogenesis
20.
Childs Nerv Syst ; 34(4): 627-638, 2018 04.
Article in English | MEDLINE | ID: mdl-29218405

ABSTRACT

OBJECTIVES: Atypical teratoid/rhabdoid tumor (AT/RT) is a rare, highly malignant tumor of the central nervous system with poor prognosis. Nowadays, multimodal management, including surgery, chemotherapy (CMT), and radiation therapy (RT), is advocated. However, AT/RT treatment with gamma knife surgery (GKS) was rarely reported. The aim of this study was to assess the efficacy and safety of GKS for the treatment of AT/RT. PATIENTS AND METHODS: Medical records of AT/RT patients who underwent surgery from 2007 to 2014 at the West China Hospital were retrospectively reviewed and statistically analyzed. RESULTS: Eighteen patients (12 males and 6 females) were presented with AT/RTs. Median age during presentation was 20.5 months (range, 4-179 months). Twelve patients were < 3 years and six patients were > 3 years. Tumor location was supratentorial in seven patients, infratentorial in ten patients, and center area of the brain in one patient. Treatments performed were as follows: surgery alone in two patients, surgery+RT in two patients, surgery+CMT in five patients, surgery+CMT+RT in two patients, and surgery+CMT+RT+GKS in seven patients. The 2-year overall survival (OS) rate and event-free survival (EFS) rate for all 18 consecutive patients were 33.3 and 27.8%, respectively. Cox regression analyses showed that multimodal management combined with GKS was an independent positive prognostic factor for OS. CONCLUSIONS: Although AT/RTs are lethal cancer types, the OS of the disease was improved by using multimodal therapeutic strategies, including surgery, CMT, and RT, combined with GKS.


Subject(s)
Antineoplastic Agents/therapeutic use , Central Nervous System Neoplasms/therapy , Combined Modality Therapy , Radiosurgery/methods , Rhabdoid Tumor/therapy , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Keratins/metabolism , Male , Mucin-1/metabolism , Nerve Tissue Proteins/metabolism , Retrospective Studies , Treatment Outcome , Vimentin/metabolism
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