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1.
Neural Regen Res ; 17(5): 1023-1033, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34558529

RESUMO

The formation of nerve bundles, which is partially regulated by neural cell adhesion molecule 1 (NCAM1), is important for neural network organization during peripheral nerve regeneration. However, little is known about how the extracellular matrix (ECM) microenvironment affects this process. Here, we seeded dorsal root ganglion tissue blocks on different ECM substrates of peripheral nerve ECM-derived matrix-gel, Matrigel, laminin 521, collagen I, and collagen IV, and observed well-aligned axon bundles growing in the peripheral nerve ECM-derived environment. We confirmed that NCAM1 is necessary but not sufficient to trigger this phenomenon. A protein interaction assay identified collagen VI as an extracellular partner of NCAM1 in the regulation of axonal fasciculation. Collagen VI interacted with NCAM1 by directly binding to the FNIII domain, thereby increasing the stability of NCAM1 at the axolemma. Our in vivo experiments on a rat sciatic nerve defect model also demonstrated orderly nerve bundle regeneration with improved projection accuracy and functional recovery after treatment with 10 mg/mL Matrigel and 20 µg/mL collagen VI. These findings suggest that the collagen VI-NCAM1 pathway plays a regulatory role in nerve bundle formation. This study was approved by the Animal Ethics Committee of Guangzhou Medical University (approval No. GY2019048) on April 30, 2019.

2.
Chemosphere ; : 132817, 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34752837

RESUMO

Indirect electrochemical oxidation by hydroxyl radicals is the predominant degradation mechanism in electrolysis with a boron-doped diamond (BDD) anode. However, this electrochemical method exhibits low reactivity in removal of hydrophilic aromatic pollutants owing to mass transfer limitation. In this study, the combination of ultraviolet light and BDD electrolysis could increase the degradation rate of hydrophilic aromatic pollutants by approximately 8-10 times relative to electrolysis alone. According to the results of the scavenging experiments and identification of benzoic acid oxidation products, surface-bound hydroxyl radical (•OH(surface)) was the primary reactive species degrading aromatic pollutants in the BDD electrolysis process, whereas freely-diffusing homogeneous hydroxyl radical (•OH(free)) was the major reactive species in the UV-assisted BDD electrolysis process. Cyclic voltammetry revealed that UV light decomposed H2O2 formed on the BDD anode surface, thus retarding O2 evolution and facilitating •OH(free) generation. This work also explored the potential application of UV-assisted BDD electrolysis in removing COD from bio-pretreated landfill leachate containing high concentrations of hydrophilic aromatic pollutants. This study shed light on the importance of the existing state of •OH on removal of pollutants during BDD electrolysis, and provided a facile and efficient UV-assisted strategy for promoting degradation of hydrophilic aromatic pollutants.

3.
Small ; : e2104112, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34816589

RESUMO

Foreign body reactions (FBR) to implants seriously impair tissue-implant integration and postoperative adhesion. The macrophage, owing to its phenotypic plasticity, is a major regulator in the formation of the inflammatory microenvironment; NF-κB signaling also plays a vital role in the process. It is hypothesized that NF-κB phosphorylation exerts a proinflammatory regulator in FBR to polylactide membranes (PLA-M) and adhesion. First, in vitro and in vivo experiments show that PLA-M induces NF-κB phosphorylation in macrophages, leading to M1 polarization and release of inflammatory factors. The inflammatory microenvironment formed due to PLA-M accelerates myofibroblast differentiation and release of collagen III and MMP2, jointly resulting in peritendinous adhesion. Therefore, JSH-23 (a selective NF-κB inhibitor)-loaded PLA membrane (JSH-23/PLA-M) is fabricated by blend electrospinning to regulate the associated M1 polarization for peritendinous anti-adhesion. JSH-23/PLA-M specifically inhibits NF-κB phosphorylation in macrophages and exhibits anti-inflammatory and anti-adhesion properties. The findings demonstrate that NF-κB phosphorylation has a critical role in PLA-induced M1 polarization and aggravating FBR to PLA-M. Additionally, JSH-23/PLA-M precisely targets modulation of NF-κB phosphorylation in FBR to break the vicious cycle in peritendinous adhesion therapy.

4.
Front Cell Dev Biol ; 9: 764275, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805171

RESUMO

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. As the main GIST drivers, gain-of-function mutations in KIT or PDGFRA are closely associated with not only tumor development and progression but also therapeutic response. In addition to the status of KIT and PDGFRA, little is known about other potential GIST-related genes. In this study, we identified the mutation profiles in 49 KIT-mutated GIST tumors using the whole exome sequencing (WES) method. Furthermore, some representative mutations were further validated in an independent GIST cohort using the SNaPshot SNP assay. We identified extensive and diverse mutations of KIT in GIST, including many undescribed variants. In addition, we revealed some new tumor-related gene mutations with unknown pathogenicity. By enrichment analyses of gene function and protein-protein interaction network construction, we showed that these genes were enriched in several important cancer- or metabolism-related signaling pathways, including PI3K-AKT,RTK-RAS, Notch, Wnt, Hippo, mTOR, AMPK, and insulin signaling. In particular, DNA repair-related genes, including MLH1, MSH6, BRCA1, BRCA2, and POLE, are frequently mutated in GISTs, suggesting that immune checkpoint blockade may have promising clinical applications for these GIST subpopulations. In conclusion, in addition to extensive and diverse mutations of KIT, some genes related to DNA-repair and cell metabolism may play important roles in the development, progression and therapeutic response of GIST.

5.
FEBS J ; 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34741776

RESUMO

Retinal pigment epithelium (RPE) cell damage is implicated in the pathogenesis of age-related macular degeneration (AMD). An increase of interferon-γ (IFN-γ) levels was observed in patients with AMD, but whether inflammatory factors are causally related to AMD progression is unclear. Here, we demonstrate a direct causal relationship between IFN-γ and RPE cell death. IFN-γ induced human retinal pigment epithelial cell (ARPE-19) death accompanied by increases in Fe2+ , reactive oxygen species, lipid peroxidation, and glutathione (GSH) depletion, which are main characteristics of ferroptosis. Mechanistically, IFN-γ upregulates the level of intracellular Fe2+ through inhibiting Fe2+ efflux protein SLC40A1 and induces GSH depletion by blocking cystine/glutamate antiporter, System xc-. At the same time, treatment with IFN-γ decreases the level of glutathione peroxidase 4 (GPx4), rendering the cells more sensitive to ferroptosis. JAK1/2 and STAT1 inhibitors could reverse the reduction of SLC7A11, GPx4 and GSH expression induced by IFN-γ, indicating IFN-γ induces ARPE-19 cell ferroptosis via activation of the JAK1-2/STAT1/SLC7A11 signaling pathway. The above results were largely confirmed in IFN-γ-treated mice in vivo. Finally, we used sodium iodate (NaIO3 )-induced retinal degeneration to further explore the role of ferroptosis in AMD in vivo. Consistent with the role of IFN-γ, treatment with NaIO3 decreased SLC7A11, GPx4 and SLC40A1 expressions. NaIO3 -induced RPE damage was accompanied by increased iron, lipid peroxidation products (4-hydroxynonenal, malondialdehyde), and GSH depletion, and ferroptosis inhibitors could reverse the above phenomenon. Taken together, our findings suggest that inhibiting ferroptosis or reducing IFN-γ may serve as a promising target for AMD.

6.
J Pharm Anal ; 11(5): 653-660, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34765279

RESUMO

A new electrochemical sensor for organophosphate pesticide (methyl-paraoxon) detection based on bifunctional cerium oxide (CeO2) nanozyme is here reported for the first time. Methyl-paraoxon was degraded into p-nitrophenol by using CeO2 with phosphatase mimicking activity. The CeO2 nanozyme-modified electrode was then synthesized to detect p-nitrophenol. Cyclic voltammetry was applied to investigate the electrochemical behavior of the modified electrode, which indicates that the signal enhancement effect may attribute to the coating of CeO2 nanozyme. The current research also studied and discussed the main parameters affecting the analytical signal, including accumulation potential, accumulation time, and pH. Under the optimum conditions, the present method provided a wider linear range from 0.1 to 100 µmol/L for methyl-paraoxon with a detection limit of 0.06 µmol/L. To validate the proof of concept, the electrochemical sensor was then successfully applied for the determination of methyl-paraoxon in three herb samples, i.e., Coix lacryma-jobi, Adenophora stricta and Semen nelumbinis. Our findings may provide new insights into the application of bifunctional nanozyme in electrochemical detection of organophosphorus pesticide.

7.
Front Genet ; 12: 698046, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603371

RESUMO

Background: Prior studies have shown that the proliferation of V79 lung fibroblast cells could be inhibited by low background radiation (LBR) in deep underground laboratory (DUGL). In the current study, we revealed further molecular changes by performing whole transcriptome analysis on the expression profiles of long non-coding RNA (lncRNA), messenger RNA (mRNA), circular RNA (circRNA) and microRNA (miRNA) in V79 cells cultured for two days in a DUGL. Methods: Whole transcriptome analysis including lncRNA, mRNAs, circ RNA and miRNA was performed in V79 cells cultured for two days in DUGL and above ground laboratory (AGL), respectively. The differentially expressed (DE) lncRNA, mRNA, circRNA, and miRNA in V79 cells were identified by the comparison between DUGL and AGL groups. Quantitative real-time polymerase chain reaction(qRT-PCR)was conducted to verify the selected RNA sequencings. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was analyzed for the DE mRNAs which enabled to predict target genes of lncRNA and host genes of circRNA. Results: With |log2(Fold-change)| ≥ 1.0 and p < 0.05, a total of 1257 mRNAs (353 mRNAs up-regulated, 904 mRNAs down-regulated), 866 lncRNAs (145 lncRNAs up-regulated, 721 lncRNAs down-regulated), and 474 circRNAs (247 circRNAs up-regulated, 227 circRNAs down-regulated) were significantly altered between the two groups. There was no significant difference in miRNA between the two groups. The altered RNA profiles were mainly discovered in lncRNAs, mRNAs and circRNAs. DE RNAs were involved in many pathways including ECM-RI, PI3K-Akt signaling, RNA transport and the cell cycle under the LBR stress of the deep underground environment. Conclusion: Taken together, these results suggest that the LBR in the DUGL could induce transcriptional repression, thus reducing metabolic process and reprogramming the overall gene expression profile in V79 cells.

8.
Mol Cancer Res ; 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34610959

RESUMO

Previous studies have demonstrated that glucocorticoid receptor ß (GRß) functions as an oncoprotein, regulating the malignant phenotypes and stem-like cell maintaining in human glioblastoma (GBM). Of the glucocorticoid receptor (GR) isoforms, GRß and GRα are highly homologous, though the mechanism underlying the distinct functions of these two isoforms in GBM has not been clarified. Here by establishing a carboxyl-terminal (COOH-terminal) deletion mutant, we determined that GRß can be ubiquitinated. We also found that its COOH terminal is essential for this ubiquitination. The mutation of a lysine to arginine at residue 733 (K733R) blocked the ubiquitination of GRß, indicating that K733 is a key site for ubiquitination. Using K733R to establish nonubiquitinated GRß, we demonstrated that ubiquitination not only regulates the stability and nuclear translocation of GRß, but is also a vital mechanism for its oncogenic functions in vitro and in vivo. Protein interaction assay further indicated that ubiquitin-specific protease 49 (USP49) is a GRß-binding protein and the interaction depends on GRß ubiquitination. USP49 knockdown resulted in a decrease of cell proliferation, invasion, and an increase of cell apoptosis. More importantly, USP49 knockdown increased ubiquitination and amplified the oncogenic effects of GRß, confirming the decisive role of ubiquitination on GRß carcinogenicity. Taken together, these findings established that ubiquitination is a vial process for GRß the execution of oncogenic functions in GBM and that the K733 site is crucial for ubiquitination of GRß. IMPLICATIONS: This work is the first identify of the activation GRß by a single lysine point-mediated ubiquitination and proteasome degradation, which determines its oncogenic functions in GBM.

10.
Chin J Nat Med ; 19(9): 700-705, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34561082

RESUMO

Biotransformation of α-asarone by Alternaria longipes CGMCC 3.2875 yielded two pairs of new neolignans, (+) (7S, 8S, 7'S, 8'R) iso-magnosalicin (1a)/(-) (7R, 8R, 7'R, 8'S) iso-magnosalicin (1b) and (+) (7R, 8R, 7'S, 8'R) magnosalicin (2a)/(-) (7S, 8S, 7'R, 8'S) magnosalicin (2b), and four known metabolites, (±) acoraminol A (3), (±) acoraminol B (4), asaraldehyde (5), and 2, 4, 5-trimethoxybenzoic acid (6). Their structures, including absolute configurations, were determined by extensive analysis of NMR spectra, X-ray crystallography, and quantum chemical ECD calculations. The cytotoxic activity and Aß42 aggregation inhibitory activity of all the compounds were evaluated. Compound 2 displayed significant anti-Aß42 aggregation activity with an inhibitory rate of 60.81% (the positive control EGCG: 69.17%). In addition, the biotransformation pathway of α-asarone by Alternaria longipes CGMCC 3.2875 was proposed.

11.
Entropy (Basel) ; 23(9)2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34573807

RESUMO

We study a scheme of thermal management where a three-qubit system assisted with a coherent auxiliary bath (CAB) is employed to implement heat management on a target thermal bath (TTB). We consider the CAB/TTB being ensemble of coherent/thermal two-level atoms (TLAs), and within the framework of collision model investigate the characteristics of steady heat current (also called target heat current (THC)) between the system and the TTB. It demonstrates that with the help of the quantum coherence of ancillae the magnitude and direction of heat current can be controlled only by adjusting the coupling strength of system-CAB. Meanwhile, we also show that the influences of quantum coherence of ancillae on the heat current strongly depend on the coupling strength of system-CAB, and the THC becomes positively/negatively correlated with the coherence magnitude of ancillae when the coupling strength below/over some critical value. Besides, the system with the CAB could serve as a multifunctional device integrating the thermal functions of heat amplifier, suppressor, switcher and refrigerator, while with thermal auxiliary bath it can only work as a thermal suppressor. Our work provides a new perspective for the design of multifunctional thermal device utilizing the resource of quantum coherence from the CAB.

12.
Org Biomol Chem ; 19(40): 8696-8700, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34581380

RESUMO

A mild and facile approach to construct various perfluoroketones via photo-catalyzed difluoroalkylation of difluoroenoxysilanes is developed. The reaction includes a strategy of combination of two fluorine-containing functional groups, which confers the reaction with characteristics like high efficiency, mild conditions, and broad scope. A variety of fluoroalkyl halides including perfluoroalkyl iodides, bromo difluoro esters and amides can be employed as radical precursors. Control experiments indicate that a single-electron transfer pathway may be involved in the reaction.

13.
Front Endocrinol (Lausanne) ; 12: 723631, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34434171

RESUMO

Objective: To determine whether papillary thyroid carcinoma (PTC) patients with benign or nonsuspicious nodules in the contralateral lobe have a higher rate of recurrence or worse survival after lobectomy compared to those without nodules in the contralateral lobe. Methods: Adult patients who underwent lobectomy and were diagnosed with unilateral PTC (2013-2015), were identified from an institutional database. Patients who previously had cytologically benign nodules or nonsuspicious nodules in the contralateral lobe comprised the contralateral nodule (CN) group. Patients who did not have nodules in the contralateral lobe comprised the unilateral nodule (UN) group. Results: 370 patients were included: 242 in the UN group and 128 in the CN group. After a median follow-up of 62 months (range, 16-85 months), recurrence was confirmed in 4.1% patients in the UN group and 5.5% patients in the CN group (p = 0.559). Clinical contralateral lobe PTC was detected in 2.9% (7/242) of patients from the UN group and 3.9% (5/128) of patients from the CN group (p = 0.601). The 5-year contralateral lobe recurrence-free survival (RFS) rates were 96.8% in the UN group and 97.4% in the CN group (p = 0.396). The 5-year loco-regional RFS rates were 98.4% in the UN group and 97.8% in the CN group (p = 0.690). The 5-year disease-specific survival rates were both 100%. Conclusion: PTC patients with benign or nonsuspicious CNs have similar recurrence and survival rates after lobectomy compared to those without CNs. CNs alone should not be an indication for total or completion thyroidectomy.

14.
Angew Chem Int Ed Engl ; 60(40): 21751-21755, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34346139

RESUMO

Singlet oxygen (1 O2 ) is an excellent active species for the selective degradation of organic pollutions. However, it is difficult to achieve high efficiency and selectivity for the generation of 1 O2 . In this work, we develop a graphitic carbon nitride supported Fe single-atoms catalyst (Fe1 /CN) containing highly uniform Fe-N4 active sites with a high Fe loading of 11.2 wt %. The Fe1 /CN achieves generation of 100 % 1 O2 by activating peroxymonosulfate (PMS), which shows an ultrahigh p-chlorophenol degradation efficiency. Density functional theory calculations results demonstrate that in contrast to Co and Ni single-atom sites, the Fe-N4 sites in Fe1 /CN adsorb the terminal O of PMS, which can facilitate the oxidization of PMS to form SO5 .- , and thereafter efficiently generate 1 O2 with 100 % selectivity. In addition, the Fe1 /CN exhibits strong resistance to inorganic ions, natural organic matter, and pH value during the degradation of organic pollutants in the presence of PMS. This work develops a novel catalyst for the 100 % selective production of 1 O2 for highly selective and efficient degradation of pollutants.

15.
Clin Ther ; 43(9): e264-e273, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34366153

RESUMO

PURPOSE: Henagliflozin is a highly selective and effective sodium glucose co-transporter (SGLT)-2 inhibitor developed for the treatment of patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate the effects of meal intake on the pharmacokinetic properties of henagliflozin, and to understand the excretion pathways of henagliflozin in humans. METHODS: In this Phase I, randomized, open-label, single-dose, two-period crossover study, 12 healthy male Chinese volunteers were randomized to receive either henagliflozin 10 mg in the fasted condition followed by henagliflozin 10 mg in the fed condition, or the reverse schedule, with the two administrations separated by a washout period of at least 7 days. Samples of blood, urine, and feces were collected and analyzed for the investigation of the pharmacokinetic profile and excretion pathways in the fasted and fed conditions. Any adverse events that occurred throughout the study were recorded for tolerability assessment. FINDINGS: After the administration of a single oral dose of henagliflozin, mean (SD) plasma AUC0-∞ and Cmax were 1200 (274) h · ng/mL and 179 (48.8) ng/mL, respectively, in the fasted state and were decreased to 971 (245) h · ng/mL and 115 (34.2) ng/mL in the fed state. The fed/fasted ratios (90% CIs) of the geometric mean values of Cmax, AUC0-t, and AUC0-∞ were 64% (54%-76%), 80% (76%-85%), and 80% (76%-85%), respectively. The median (range) Tmax was prolonged from 1.5 (1-3) hours in the fasted condition to 2 (1.5-6) hours in the fed condition. Mass-balance testing revealed that henagliflozin was eliminated primarily as the parent drug in feces and as glucuronide metabolites in urine. In the fasted state, the cumulative excretion percentages of the parent drug and its metabolites to dose in feces and urine were 40.6% and 33.9%, respectively. The values in the fed condition were changed to 50.4% and 25.5%, respectively. These findings suggest that postprandial administration decreases the absorption rate and the extent of henagliflozin exposure in humans, but has no effect on the metabolism or elimination of the drug. IMPLICATIONS: In the present study, the consumption of a high-fat meal prior to henagliflozin administration was associated with reductions in AUC0-∞ and Cmax of 19.4% and 36.4%, respectively. However, based on the analysis of the pharmacokinetic/pharmacodynamic findings on henagliflozin, this slight change may not have clinical significance. Mass balance of henagliflozin in humans was achieved with ∼75% of the administered dose recovered in excretions within 4 days after administration whether in the fasted or fed state. These findings suggest that henagliflozin tablets can be administered with or without food.

16.
Int J Rheum Dis ; 24(10): 1247-1256, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34314100

RESUMO

BACKGROUND: Takayasu arteritis (TAK) is a rare large vessel vasculitis, and epidemiological data on TAK are lacking in China. Thus, we designed this study to estimate the TAK prevalence and incidence in residential Shanghai, China. METHODS: Data on diagnosed TAK cases aged over 16 years were retrieved from 22 tertiary hospitals in Shanghai through hospital electronic medical record systems between January 1, 2015 and December 31, 2017 to estimate the prevalence and incidence. A systematic literature review based on searches in PubMed, Ovid-Medline, Excerpta Medica Database (EMBASE), Web of Science, and China National Knowledge Infrastructure (CNKI) was performed to summarize TAK distribution across the world. RESULTS: In total 102 TAK patients, with 64% female, were identified. The point prevalence (2015-2017) was 7.01 (95% CI 5.65-8.37) cases per million, and the mean annual incidence was 2.33 (1.97-3.21) cases per million. The average age of TAK patients was 44 ± 16 years, with the highest prevalence (11.59 [9.23-19.50] cases per million) and incidence (3.55 [0.72 3.74] cases per million) in the 16 to 34 years population. Seventeen reports were included in the system review, showing that the epidemiology of TAK varied greatly across the world. The incidence and prevalence were both relatively higher in Asian countries, with the prevalence ranging 3.3-40 cases per million and annual incidence ranging 0.34-2.4 cases per million. CONCLUSIONS: The prevalence and incidence of TAK in Shanghai was at moderate to high levels among the previous reports. The disease burden varied globally among racial populations.

17.
Sci Total Environ ; 797: 149201, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34303978

RESUMO

Microplastics (MPs) are the significant environmental factor for bioavailability of hydrophobic organic contaminants (HOCs) in aquatic environments. Nevertheless, the bioavailability of microplastic-associated HOCs remains unclear. In this research, the freely dissolved pyrene concentrations were kept stable with passive dosing devices, and the pyrene content in D. magna tissues as well as D. magna immobilization were analyzed to quantify bioavailability of pyrene (a representative HOC) associated with naturally-aged polystyrene (PS) MPs. Furthermore, the uptake mechanisms of pyrene associated with MPs of different sizes were explored by investigating the distribution of MPs in D. magna tissues with scanning electron microscopy. Especially, a new schematic model of bioavailability process was established. The results demonstrated that a part of pyrene associated with 0-1.5 µm MPs could directly cross cell membrane through endocytosis from intestine and exposure solutions to D. magna tissues except the 10-60 and 60-230 µm MPs. The bioavailability of microplastic-associated pyrene was ordered as 0-1.5 µm (20.0-21.6%) > 10-60 µm (10.7-13.8%) > 60-230 µm MPs (6.0-9.8%), which were essentially resulted from the difference in uptake mechanisms of pyrene associated with MPs of different sizes. This work suggests that the bioavailability of microplastic-associated HOCs should be considered when assessing water quality and environmental risk of HOCs in natural waters.


Assuntos
Daphnia , Poluentes Químicos da Água , Animais , Disponibilidade Biológica , Microplásticos , Plásticos , Pirenos/análise , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
18.
Histol Histopathol ; : 18366, 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34323284

RESUMO

Glioblastoma (GBM) is the most common and aggressive brain tumor in adults, characterized by diffuse infiltration, dysplasia, and resistance to therapy. Metabolic remodeling and immunosuppression are typical events which contribute to GBM progression, but the molecular link between these two events remains largely undetermined. Studies have shown that high levels of transforming growth factor-ß (TGF-ß) and its receptors are associated with glioma malignancy and a poor prognosis. TGF-ß plays an important role in cell metabolism and immunity. During tumorigenesis, TGF-ß induces a shift in cell metabolism from oxidative phosphorylation to aerobic glycolysis, providing a favorable environment for tumor growth. Locally, TGF-ß creates an immunosuppressive microenvironment and promotes the malignant phenotype of GBM. In this review, we aim to link GBM aerobic glycolysis and immunosuppression through TGF-ß to provide new ideas for the study of GBM.

19.
Sleep Breath ; 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34291360

RESUMO

OBJECTIVE: To investigate the correlation between obstructive sleep apnea (OSA) and coagulation status and to speculate on the underlying mechanism in children with OSA. METHODS: We divided 345 children with OSA (age 2-14 years) into four groups according to the apnea-hypopnea index (AHI). We compared platelet (PLT) and coagulation parameters among groups. Correlations between the polysomnography parameters and coagulation parameters were investigated. RESULTS: Children with OSA had higher PLT counts than those without OSA (P < 0.001), while no significant difference was observed in prothrombin time, international normalized ratio, activated partial thromboplastin time, thrombin time, or fibrinogen among children with/without OSA. In linear regression analysis, the AHI and oxygen desaturation index (ODI) presented positive correlation with the PLT count (R2 = 0.155, beta = 0.307, P < 0.001 and R2 = 0.113, beta = 0.262, P < 0.001), and there was no correlation among the AHI, ODI, and other coagulation parameters. The minimum and mean oxygen saturation of arterial blood manifested negative correlation with the PLT count (R2 = 0.076, beta = - 0.116, P = 0.034 and R2 = 0.083, beta = - 0.140, P = 0.008, respectively). CONCLUSIONS: Children with OSA have a higher PLT count, positively correlated with OSA severity, and no evidence of coagulation disorder.

20.
World J Gastroenterol ; 27(26): 4221-4235, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34326621

RESUMO

BACKGROUND: Ubiquitin-specific protease 15 (USP15) is an important member of the ubiquitin-specific protease family, the largest deubiquitinase subfamily, whose expression is dysregulated in many types of cancer. However, the biological function and the underlying mechanisms of USP15 in gastric cancer (GC) progression have not been elucidated. AIM: To explore the biological role and underlying mechanisms of USP15 in GC progression. METHODS: Bioinformatics databases and western blot analysis were utilized to determine the expression of USP15 in GC. Immunohistochemistry was performed to evaluate the correlation between USP15 expression and clinicopathological characteristics of patients with GC. A loss- and gain-of-function experiment was used to investigate the biological effects of USP15 on GC carcinogenesis. RNA sequencing, immunofluorescence, and western blotting were performed to explore the potential mechanism by which USP15 exerts its oncogenic functions. RESULTS: USP15 was up-regulated in GC tissue and cell lines. The expression level of USP15 was positively correlated with clinical characteristics (tumor size, depth of invasion, lymph node involvement, tumor-node-metastasis stage, perineural invasion, and vascular invasion), and was related to poor prognosis. USP15 knockdown significantly inhibited cell proliferation, invasion and epithelial-mesenchymal transition (EMT) of GC in vitro, while overexpression of USP15 promoted these processes. Knockdown of USP15 inhibited tumor growth in vivo. Mechanistically, RNA sequencing analysis showed that USP15 regulated the Wnt signaling pathway in GC. Western blotting confirmed that USP15 silencing led to significant down-regulation of ß-catenin and Wnt/ß-catenin downstream genes (c-myc and cyclin D1), while overexpression of USP15 yielded an opposite result and USP15 mutation had no change. Immunofluorescence indicated that USP15 promoted nuclear translocation of ß-catenin, suggesting activation of the Wnt/ß-catenin signaling pathway, which may be the critical mechanism promoting GC progression. Finally, rescue experiments showed that the effect of USP15 on gastric cancer progression was dependent on Wnt/ß-catenin pathway. CONCLUSION: USP15 promotes cell proliferation, invasion and EMT progression of GC via regulating the Wnt/ß-catenin pathway, which suggests that USP15 is a novel potential therapeutic target for GC.


Assuntos
Neoplasias Gástricas , Via de Sinalização Wnt , Linhagem Celular Tumoral , Proliferação de Células , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica/genética , Neoplasias Gástricas/genética , Proteases Específicas de Ubiquitina/genética , beta Catenina/metabolismo
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