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1.
Front Immunol ; 12: 774323, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777393

RESUMO

J subgroup avian leukosis virus (ALV-J) infection causes serious immunosuppression problems, leading to hematopoietic malignancy tumors in chicken. It has been demonstrated that interferon-stimulated genes (ISGs) could limit ALV-J replication; nevertheless, the underlying mechanisms remain obscure. Here, we demonstrate that Long-chain Acyl-CoA synthetase 1 (ACSL1) is an interferon (IFN)-stimulated gene that specifically restricts the replication of ALV-J due to the higher IFN-I production. More importantly, ACSL1 induces primary monocyte-derived macrophages (MDMs) to pro-inflammatory phenotypic states during ALV-J infection, and ACSL1 mediates apoptosis through the PI3K/Akt signaling pathway in ALV-J-infected primary monocyte-derived macrophages (MDMs). Overall, these results provide evidence that ACSL1 contributes to the antiviral response against ALV-J.

2.
Cell Death Dis ; 12(10): 903, 2021 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-34601496

RESUMO

As oncogenes and tumor suppressor genes, long non-coding RNAs (lncRNAs) regulate the biological behavior of gastric cancer (GC) cells such as proliferation, invasion, and metastasis through various signal pathways. At present, although numerous lncRNAs that significantly influence the development and progression of GC have been identified, a considerable number of them have not been found and studied yet. In this study, we identified a new lncRNA derived from pseudogenes WFDC21P, which have not been reported in any previous GC study. LncRNA WFDC21P was significantly upregulated in GC cells and tissues, and clinically associated with the pathological stages of advanced GC. WFDC21P promoted proliferation and metastasis of GC cells both in vitro and in vivo. LncRNA WFDC21P was directly bound to GTPase Ran and it promoted the activity of the Akt/GSK3ß/ß-catenin pathway. Forkhead Box P3 (FOXP3), as a transcription factor of WFDC21P, was directly bound to the promoter region and it positively regulated the transcription of WFDC21P. This finding may provide a novel biomarker and therapeutic target for GC.

3.
Eur Radiol ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34643780

RESUMO

OBJECTIVES: To compare the visibility of intracranial aneurysm wall and thickness quantification between 7 and 3 T vessel wall imaging and evaluate the association between aneurysm size and wall thickness. METHODS: Twenty-nine patients with 29 unruptured intracranial aneurysms were prospectively recruited for 3D T1-weighted vessel wall MRI at both 3 T and 7 T with 0.53 mm (3 T) and 0.4 mm (7 T) isotropic resolution, respectively. Two neuroradiologists independently evaluated wall visibility (0-5 Likert scale), quantified the apparent wall thickness (AWT) using a semi-automated full-width-half-maximum method, calculated wall sharpness, and measured the wall-to-lumen contrast ratio (CRwall/lumen). RESULTS: Twenty-four patients with 24 aneurysms were included in this study. 7 T achieved significantly better aneurysm wall visibility than 3 T (3.6 ± 1.1 vs 2.7 ± 0.8, p = 0.003). AWT measured on 3 T and 7 T had a good correlation (averaged r = 0.63 ± 0.19). However, AWT on 3 T was 15% thicker than that on 7 T (0.52 ± 0.07 mm vs 0.45 ± 0.05 mm, p < 0.001). Wall sharpness on 7 T was 57% higher than that on 3 T (1.95 ± 0.32 mm-1 vs 1.24 ± 0.15 mm-1, p < 0.001). CRwall/lumen on 3 T and 7 T was comparable (p = 0.424). AWT on 7 T was positively correlated with aneurysm size (saccular: r = 0.58, q = 0.046; fusiform: r = 0.67, q = 0.049). CONCLUSIONS: 7 T provides better visualization of intracranial aneurysm wall with higher sharpness than 3 T. 3 T overestimates the wall thickness relative to 7 T. Aneurysm wall thickness is positively correlated with aneurysm size. 7 T MRI is a promising tool to evaluate aneurysm wall in vivo. KEY POINTS: • 7 T provides better visualization of intracranial aneurysm wall with higher sharpness than 3 T. • 3 T overestimates the wall thickness comparing with 7 T. • Aneurysm wall thickness is positively correlated with aneurysm size.

5.
Sci Total Environ ; 807(Pt 2): 150519, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34610409

RESUMO

The urbanization and development of Tibetan Plateau (TP) probably results in a significant contamination of organic pollutants, such as organophosphate flame retardants (OPFRs). However, there is a lack of monitoring and evaluation of their occurrence and risks in the soil of TP. We investigated the concentrations, vertical distributions, potential sources, and ecological risks of OPFRs in soil profiles from four regions of TP, China. The total concentrations of OPFRs in all soil samples ranged from 1.35 to 126 ng/g with a median of 12.6 ng/g. Relatively high concentrations were discovered in the top soils from Lhasa, suggesting a rising contamination around cities of TP due to anthropogenic disturbance. Tri-n-butyl phosphate (TNBP) was the dominant OPFRs followed by tris(2-chloroethyl) phosphate (TCEP). Vertical distribution of ΣOPFRs was discovered, especially at site Lhasa. Source apportionment based on principle component analysis and correlation analysis suggests that OPFRs in the TP soil mainly originate from atmospheric transport, while some OPFRs in the top soil may be also influenced by nearby sources. The vertical distributions of OPFRs in soil may be influenced by both soil and chemical properties, as well as their use. The ecological risk quotients (RQs) of 6 OPFRs in the TP soil were calculated, and most of their ecological risks were relatively low or negligible. However, for the worst-case scenario calculated by the 95th percentile concentrations, TNBP and tris(2-chloro-isopropyl) phosphate (TCIPP) at site Lhasa and cresyl diphenyl phosphate (CDP) at site Nagri had moderate risks. More attentions should be paid to the Tibetan Plateau in the future due to the rising ecological risks of OPFRs, especially to the areas around cities.

6.
Circ Res ; 129(12): 1141-1157, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34704457

RESUMO

RATIONALE: The NLRP3 (NLR [NOD-like receptor] family, pyrin domain containing 3) inflammasome is an important driver of atherosclerosis. Our previous study shows that chaperone-mediated autophagy (CMA), one of the main lysosomal degradative process, has a regulatory role in lipid metabolism of macrophages. However, whether the NLRP3 inflammasome is regulated by CMA, and the role of CMA in atherosclerosis remains unclear. OBJECTIVE: To determine the role of CMA in the regulation of NLRP3 inflammasome and atherosclerosis. METHODS AND RESULTS: The expression of CMA marker, LAMP-2A (lysosome-associated membrane protein type 2A), was first analyzed in ApoE-/- mouse aortas and human coronary atherosclerotic plaques, and a significant downregulation of LAMP-2A in advanced atherosclerosis in both mice and humans was observed. To selectively block CMA, we generated macrophage-specific conditional LAMP-2A knockout mouse strains in C57BL/6 mice and ApoE-/- mice. Deletion of macrophage LAMP-2A accelerated atherosclerotic lesion formation in the aortic root and the whole aorta in ApoE-/- mice. Mechanistically, LAMP-2A deficiency promoted NLRP3 inflammasome activation and subsequent release of mature IL (interleukin)-1ß in macrophages and atherosclerotic plaques. Furthermore, gain-of-function studies verified that restoration of LAMP-2A levels in LAMP-2A-deficient macrophages greatly attenuated NLRP3 inflammasome activation. Importantly, we identified the NLRP3 protein as a CMA substrate and demonstrated that LAMP-2A deficiency did not affect the NLRP3 mRNA levels but hindered degradation of the NLRP3 protein through CMA pathway. CONCLUSIONS: CMA function becomes impaired during the progression of atherosclerosis, which increases NLRP3 inflammasome activation and secretion of IL-1ß, promoting vascular inflammation and atherosclerosis progression. Our study unveils a new mechanism by which NLRP3 inflammasome is regulated in macrophages and atherosclerosis, thus providing a new insight into the role of autophagy-lysosomal pathway in atherosclerosis. Pharmacological activation of CMA may provide a novel therapeutic strategy for atherosclerosis and other NLRP3 inflammasome/IL-1ß-driven diseases.

7.
Front Neurol ; 12: 700476, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484103

RESUMO

Lenticulostriate arteries (LSAs) supply blood to the basal ganglia region. Its lesion causes lacunar stroke and resulting neurological syndromes. However, due to its small caliber and large individual variance, the evaluation of LSAs was limited to descriptive and objective measurements. In this study, we aimed to develop a post-processing method to quantify LSAs in subcortical regions and compare their vascular volume to conventional LSA measurements. A processing pipeline was designed to extract subcortical areas in individual spaces while screening out vessels. The vascular volume of LSAs in the subcortical region was calculated from time-of-flight-magnetic resonance angiography (TOF-MRA) at 7 Tesla. The reproducibility was tested to be good for the vascular volume (n = 5, ICCA = 0.84). Comparing the results to conventional measurements, the vascular volume was significantly correlated with the number of branches (r = 0.402, p < 0.001) and the length (r = 0.246, p = 0.032) of LSAs. By applying the method to a group of healthy volunteers (n = 40), we found that most LSAs crossing through the putamen which thereby has the highest vascular density among subcortical nuclei. In general, we proposed a semi-automated processing pipeline for quantifying the vascular volume of LSAs in subcortical regions. The novel method was tested to be robust and provided reasonable results. This method revealed spatial relationships among the perforating arteries and basal ganglia. The vascular volume can be used to evaluated blood supply of subcortical regions, benefiting the radiologic evaluation of neurodegenerative diseases caused by small vascular lesions.

8.
Front Cardiovasc Med ; 8: 690846, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485398

RESUMO

Filamins (FLNs) are actin cross-linking proteins, and as scaffolding proteins, FLNs are closely associated with the stabilization of the cytoskeleton. Nevertheless, the biological importance of FLNs in aortic dissection (AD) has not been well-elucidated. In this study, we first reanalyzed datasets downloaded from the Gene Expression Omnibus (GEO) database, and we found that in addition to the extracellular matrix, the actin cytoskeleton is a key structure associated with AD. Given that FLNs are involved in remodeling the cytoskeleton to affect cellular functions, we measured their expression levels in the aortas of patients with Stanford type A AD (TAAD). Our results showed that the mRNA and protein levels of FLNA were consistently decreased in dissected aortas of both humans and mice, while the FLNB protein level was upregulated despite decreased FLNB mRNA levels, and comparable expression levels of FLNC were observed between groups. Furthermore, the immunohistochemistry results demonstrated that FLNA was highly expressed in smooth muscle cells (SMCs) of aorta in non-AD samples, and downregulated in the medial layer of the dissected aortas of humans and mice. Moreover, we revealed that FOS and JUN, forming a dimeric transcription factor called AP-1 (activating protein-1), were positively correlated with the expression of FLNA in aorta. Either overexpression of FOS or JUN alone, or overexpression of FOS and JUN together, facilitated the expression of FLNA in primary cultured human aortic SMCs. In the present study, we not only detected the expression pattern of FLNs in aortas of humans and mice with or without AD, but we also found that the expression of FLNA in the AD samples was significantly reduced and that AP-1 might regulate the expression of FLNA. Our findings will contribute to the elucidation of the pathological mechanisms of AD and provide potential therapeutic targets for AD.

10.
Front Cell Infect Microbiol ; 11: 748795, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568100

RESUMO

Avian leukosis virus subgroup J (ALV-J) is an oncogenic retrovirus that causes immunosuppression and neoplastic diseases in poultry. Cytokine signal-transduction inhibitor molecule 3 (SOCS3) is an important negative regulator of the JAK2/STAT3 signaling pathway and plays certain roles in ALV-J infection. It is of significance to confirm the roles of SOCS3 in ALV-J infection and study how this gene affects ALV-J infection. In this study, we assessed the expression of the SOCS3 gene in vivo and in vitro, and investigated the roles of SOCS3 in ALV-J infection using overexpressed or interfered assays with the SOCS3 in DF-1 cells. The results showed that the SOCS3 expression of ALV-J infected chickens was different from uninfected chickens in the spleen, thymus and cecal tonsil. Further, SOCS3 is mainly expressed in the nucleus as determined by immunofluorescence assay. Overexpression of SOCS3 in DF-1 cells promoted the replication of ALV-J virus, and the expression of interferons (IFNα and INFß), inflammatory factors (IL-6 and TNFα) along with interferon-stimulating genes (CH25H, MX1, OASL, and ZAP). Conversely, interference of SOCS3 showed the opposite results. We also observed that SOCS3 promoted ALV-J virus replication by inhibiting JAK2/STAT3 phosphorylation. In conclusion, SOCS3 promotes ALV-J replication via inhibiting the phosphorylation of the JAK2/STAT3 signaling pathway. These results would advance further understanding of the persistent infection and the viral immune evasion of the ALV-J virus.


Assuntos
Vírus da Leucose Aviária , Leucose Aviária , Doenças das Aves Domésticas , Animais , Galinhas , Fosforilação , Replicação Viral
11.
Front Cardiovasc Med ; 8: 734514, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513962

RESUMO

Background: Exosomes in cardiovascular diseases (CVDs) have become an active research field with substantial value and potential. Nevertheless, there are few bibliometric studies in this field. We aimed to visualize the research hotspots and trends of exosomes in CVDs using a bibliometric analysis to help understand the future development of basic and clinical research. Methods: The articles and reviews regarding exosomes in the CVDs were culled from the Web of Science Core Collection, and knowledge maps were generated using CiteSpace and VOSviewer software. Results: A total of 1,039 articles were included. The number of exosome articles in the CVDs increased yearly. These publications came from 60 countries/regions, led by the US and China. The primary research institutions were Shanghai Jiao Tong University and Nanjing Medical University. Circulation Research was the journal and co-cited journal with the most studies. We identified 473 authors among which Lucio Barile had the most significant number of articles and Thery C was co-cited most often. After analysis, the most common keywords are myocardium infarction, microRNA and mesenchymal stem cells. Ischemic heart disease, pathogenesis, regeneration, stem cells, targeted therapy, biomarkers, cardiac protection, and others are current and developing areas of study. Conclusion: We identified the research hotspots and trends of exosomes in CVDs using bibliometric and visual methods. Research on exosomes is flourishing in the cardiovascular medicine. Regenerative medicine, exosome engineering, delivery vehicles, and biomarkers will likely become the focus of future research.

12.
Exp Ther Med ; 22(4): 1152, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34504597

RESUMO

The aging of the population has led to an annual increase in the incidence of vascular calcification (VC). Specific protein 1 (Sp1) is a transcriptional activator that serves an important role in VC. The deacetylation of transcription factors represses their binding to the promoters of downstream genes, thereby causing their downregulation. The present study aimed to investigate the role of deacetylated Sp1 in the development of VC. In the present study, western blotting and immunoprecipitation (IP) were performed to detect the protein levels of acetylated Sp1. Western blotting and immunofluorescence staining were used to analyze phenotypic switching in vascular smooth muscle cells (VSMCs). Alizarin red S, alkaline phosphatase (ALP) activity and calcium content assays were used to assess calcium deposition in VSMCs. Western blotting, flow cytometry, TUNEL staining and caspase3 activity assay were used to evaluate apoptosis of VSMCs. Chromatin immunoprecipitation (ChIP) assay was used to detect Sp1 binding to the BMP2 promoter. The results indicated that, in a ß-glycerophosphate (ß-GP)-induced VSMC calcification model, the level of acetylated Sp1 was increased. Western blotting and immunofluorescence staining results showed that, compared with the Sp1 overexpression group (Sp1-WT), deacetylated Sp1 (Sp1-K704A) downregulated the expression of osteogenic markers runt-related transcription factor 2 (Runx2) and bone morphogenetic protein 2 (BMP2), and upregulated the expression of contraction marker α-smooth muscle actin (α-SMA) and calponin 1. In addition, deacetylated Sp1 also reduced the ALP activity and calcium content of calcified VSMCs, and the Alizarin red S assay revealed that the calcium crystallization of Sp1-K704A group was markedly decreased. Western blotting, flow cytometry, TUNEL staining and caspase-3 activity assay were detected to indicate that the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein ratio was increased, and caspase-3 activity and the apoptotic rate of VSMCs were decreased, in the Sp1-K704A group, as compared with the Sp1-WT group. ChIP assay revealed that Sp1 binding to the BMP2 promoter was downregulated in the Sp1-K704A group, compared with that in theSp1-WT group. In conclusion, a deacetylated mutant of Sp1 decreased Sp1 binding to the BMP2 promoter, thus decreasing apoptosis, phenotypic switching and calcium deposition in calcified VSMCs. This finding may indicate potential therapeutic targets for VC.

13.
Front Immunol ; 12: 731933, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484243

RESUMO

Background: Pyroptosis is a new programmed cell death discovered in recent years. Pyroptosis plays an important role in various diseases. Nevertheless, there are few bibliometric analysis systematically studies this field. We aimed to visualize the research hotspots and trends of pyroptosis using a bibliometric analysis to help understand the future development of basic and clinical research. Methods: The articles and reviews regarding pyroptosis were culled from Web of Science Core Collection. Countries, institutions, authors, references and keywords in this field were visually analyzed by using CtieSpace and VOSviewer software. Results: A total of 2845 articles and reviews were included. The number of articles regarding pyroptosis significantly increased yearly. These publications mainly come from 70 countries led by China and the USA and 418 institutions. We identified 605 authors, among which Thirumaladevi Kanneganti had the most significant number of articles, and Shi JJ was co-cited most often. Frontiers in immunology was the journal with the most studies, and Nature was the most commonly cited journal. After analysis, the most common keywords are nod like receptor family pyrin domain containing 3 inflammasome, apoptosis, cell death, gasdermin D, mechanism, caspase-1, and others are current and developing areas of study. Conclusion: Research on the pyroptosis is flourishing. Cooperation and exchanges between countries and institutions must be strengthened in the future. The related pathway mechanism of pyroptosis, the relationship between pyroptosis and other types of programmed cell deaths as well as the role of pyroptosis in various diseases have been the focus of current research and developmental trends in the future research.

14.
Phytother Res ; 35(11): 6310-6323, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34514657

RESUMO

Overactivation of TGF-ß/ALK5/Smad signaling pathway has been observed in the advanced stage of various human malignancies. As a key component of TGF-ß/ALK5/Smad signaling pathway transduction, TGF-ß type I receptor (also known as ALK5) has emerged as a promising therapeutic target for cancer treatment. In this study, to discover a novel ALK5 inhibitor, a commercial natural products library was screened using docking-based virtual screening, followed by luciferase reporter assay. A flavonoid glycoside kaempferol 3-O-gentiobioside (KPF 3-O-G) was identified as a potent ALK5 inhibitor through directly bound to the ATP-site of ALK5, resulting in the inhibitory effects on phosphorylation and translocation of Smad2 and expression of Smad4. Additionally, we found that KPF 3-O-G reduced cell proliferation and inhibited TGF-ß-induced cell migration and invasion. Moreover, western blotting and immunofluorescent analysis showed that KPF 3-O-G significantly reversed the TGF-ß-induced EMT biomarkers, including upregulation of E-cadherin and downregulation of N-cadherin, vimentin, and snail. In vivo study showed that KPF 3-O-G administration reduced tumor growth in human ovarian cancer xenograft mouse model, without obvious toxic effect. This study provided novel insight into the anticancer effects of KPF-3-O-G and indicated that KPF-3-O-G might be developed as potential therapeutics for cancer treatment after further validation.


Assuntos
Transição Epitelial-Mesenquimal , Quempferóis , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Camundongos , Receptor do Fator de Crescimento Transformador beta Tipo I , Transdução de Sinais , Fator de Crescimento Transformador beta
15.
Artigo em Inglês | MEDLINE | ID: mdl-34355321

RESUMO

As an inevitable industrial by-product, polyaluminum chloride residue (PACR) will cause serious harm to the environment if directly buried and dumped. The aim of this paper was searched a new economical, environmental, and practical way of utilization for PACR. In this paper, a novel non-burning PACR compound filler was made from mainly PACR. The prepared compound filler has excellent physical properties and phosphate adsorption efficiency of up to 99.9%. Static adsorption experiments showed that the adsorption process of phosphorus by the compound filler conformed to the pseudo-second-order kinetic model and intra-particle diffusion model. Langmuir and Freundlich isotherm models described the phosphorus adsorption process well, and the maximum phosphate adsorption capacity arrived at 42.55 mg/g. The phosphate adsorption by the compound filler is a spontaneous endothermic process. The main mechanisms are ligand exchange and Lewis acid-base interactions; calcium and aluminum play important roles in the adsorption of phosphorus by the compound filler. Dynamic column experiments showed that as much as 90% of the phosphorus removal by compound filler, and the phosphorus concentration decreased from 1 to ~0.1mg/L. The results provide a new waste resource utilization method for PACR and show the good application potential of prepared compound filler in constructed wetlands.

16.
Cell Death Differ ; 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34363017

RESUMO

Hematopoietic stem cell (HSC) fate is tightly controlled by various regulators, whereas the underlying mechanism has not been fully uncovered due to the high heterogeneity of these populations. In this study, we identify tetraspanin CD63 as a novel functional marker of HSCs in mice. We show that CD63 is unevenly expressed on the cell surface in HSC populations. Importantly, HSCs with high CD63 expression (CD63hi) are more quiescent and have more robust self-renewal and myeloid differentiation abilities than those with negative/low CD63 expression (CD63-/lo). On the other hand, using CD63 knockout mice, we find that loss of CD63 leads to reduced HSC numbers in the bone marrow. In addition, CD63-deficient HSCs exhibit impaired quiescence and long-term repopulating capacity, accompanied by increased sensitivity to irradiation and 5-fluorouracil treatment. Further investigations demonstrate that CD63 is required to sustain TGFß signaling activity through its interaction with TGFß receptors I and II, thereby playing an important role in regulating the quiescence of HSCs. Collectively, our data not only reveal a previously unrecognized role of CD63 but also provide us with new insights into HSC heterogeneity.

17.
iScience ; 24(8): 102884, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34401668

RESUMO

Catalytic transfer hydrogenation (CTH) of biomass-derived furfural (FAL) to furfuryl alcohol is recognized as one of the most versatile techniques for biomass valorization. However, the irreversible sintering of metal sites under the high-temperature reaction or during the coke removal regeneration process poses a serious concern. Herein, we present a silicalite-1-confined ultrasmall CuO structure (CuO@silicalite-1) and then compared its catalytic efficiency against conventional surface-supported CuO structure (CuO/silicalite-1) toward CTF of FAL with alcohols. Characterization results revealed that CuO nanoparticles encapsulated within the silicalite-1 matrix are ∼1.3 nm in size in CuO@silicalite-1, exhibiting better dispersion as compared to that in the CuO/silicalite-1. The CuO@silicalite-1, as a result, exhibited nearly 100-fold higher Cu-mass-based activity than the CuO/silicalite-1 counterpart. More importantly, the activity of the CuO@silicalite-1 catalyst can be regenerated via facile calcination to remove the surface-bound carbon deposits, unlike the CuO/silicalite-1 that suffered severe deactivation after use and cannot be effectively regenerated.

18.
Free Radic Biol Med ; 174: 144-156, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34389464

RESUMO

Ionizing radiation (IR)-induced excessive reactive oxygen species (ROS) is an important contributor of the injury of hematopoietic system. Grape seed proanthocyanidin extract (GSPE) is a new type of antioxidant, whereas whether it could ameliorate IR-induced hematopoietic injury remains unclear. Here, we show that GSPE treatment improves the survival of irradiated mice and alleviates IR-induced myelosuppression. Meanwhile, the hematopoietic reconstituting ability of hematopoietic stem cells (HSCs) in mice following irradiation exposure is significantly increased after GSPE treatment. Furthermore, GSPE treatment can reduce IR-induced ROS production and relieve DNA damage and apoptosis in hematopoietic stem progenitor cells (HSPCs). Interestingly, we find that a critical antioxidant-associated gene fokhead box transcription factor O1 (Foxo1) is significantly decreased in HSPCs after irradiation. Consistently, hematopoietic specific deletion of Foxo1 increases the radiosensitivity of mice. Further investigations reveal that GSPE treatment specifically upregulates the expression of Foxo1, as well as its target genes superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2) and catalase (CAT). Importantly, Foxo1 deficiency largely abolishes the radioprotection of GSPE on HSPCs. Collectively, our data demonstrate that GSPE plays an important role in ameliorating IR-induced HSPC injury via the Foxo1-mediated pathway. Therefore, GSPE may be used as a promising radioprotective agent.


Assuntos
Extrato de Sementes de Uva , Proantocianidinas , Animais , Antioxidantes/farmacologia , Proteína Forkhead Box O1/genética , Extrato de Sementes de Uva/farmacologia , Células-Tronco Hematopoéticas , Camundongos , Proantocianidinas/farmacologia , Radiação Ionizante
19.
J Neurointerv Surg ; 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34452988

RESUMO

BACKGROUND: This study was performed to quantify intracranial aneurysm wall thickness (AWT) and enhancement using 7T MRI, and their relationship with aneurysm size and type. METHODS: 27 patients with 29 intracranial aneurysms were included. Three-dimensional T1 weighted pre- and post-contrast fast spin echo with 0.4 mm isotropic resolution was used. AWT was defined as the full width at half maximum on profiles of signal intensity across the aneurysm wall on pre-contrast images. Enhancement ratio (ER) was defined as the signal intensity of the aneurysm wall over that of the brain parenchyma. The relationships between AWT, ER, and aneurysm size and type were investigated. RESULTS: 7T MRI revealed large variations in AWT (range 0.11-1.24 mm). Large aneurysms (>7 mm) had thicker walls than small aneurysms (≤7 mm) (0.49±0.05 vs 0.41±0.05 mm, p<0.001). AWT was similar between saccular and fusiform aneurysms (p=0.546). Within each aneurysm, a thicker aneurysm wall was associated with increased enhancement in 28 of 29 aneurysms (average r=0.65, p<0.05). Thicker walls were observed in enhanced segments (ER >1) than in non-enhanced segments (0.53±0.09 vs 0.38±0.07 mm, p<0.001). CONCLUSION: Improved image quality at 7T allowed quantification of intracranial AWT and enhancement. A thicker aneurysm wall was observed in larger aneurysms and was associated with stronger enhancement.

20.
Front Aging Neurosci ; 13: 620763, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34295237

RESUMO

Objective: Severe carotid artery stenosis (CAS) can lead to atrophy of gray matter (GM) and memory impairment; however, the underlying mechanism is unknown. Thus, we aimed to identify memory impairment and GM atrophy and explore the possible correlation between them in patients with asymptomatic severe CAS. Methods: Twenty-four patients with asymptomatic severe CAS and 10 healthy controls completed the mini-mental state examination (MMSE) and clinical memory scale (CMS) and underwent 7T magnetic resonance imaging (MRI) scan. Field intensity inhomogeneities were corrected. Images were processed using VBM8, and GM images were flipped. First, 11 flipped and 10 non-flipped images of patients with unilateral CAS and 5 flipped and 5 non-flipped images of controls were pre-processed using DARTEL algorithm and analyzed using an analysis of variance (ANOVA). Second, flipped and non-flipped images of unilateral patients were similarly pre-processed and analyzed using the paired t-test. Third, pre-processed non-flipped GM images and CMS scores of 24 patients were analyzed by multiple regression analysis. Nuisance variables were corrected accordingly. Results: Basic information was well matched between patients and controls. MMSE scores of patients were in the normal range; however, memory function was significantly reduced (all P < 0.05). GM volumes of patients were significantly reduced in the anterior circulation regions. The stenosis-side hemispheres showed greater atrophy. GM volumes of the left pars opercularis, pars triangularis, and middle frontal gyrus were strongly positively correlated with the total scores of CMS (all r > 0.7, P = 0.001). Additionally, the left middle frontal gyrus was strongly positively correlated with associative memory (r = 0.853, P = 0.001). The left pars opercularis was moderately positively correlated with semantic memory (r = 0.695, P = 0.001). Conclusion: Patients with asymptomatic CAS suffer from memory impairment. Bilateral anterior circulation regions showed extensive atrophy. The hemisphere with stenosis showed severer atrophy. Memory impairment in patients may be related to atrophy of the left frontal gyrus and atrophy of different regions may result in different memory impairments.

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