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1.
Bioeng Transl Med ; 9(2): e10626, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38435827

RESUMO

Increased pulmonary vascular permeability is a characteristic feature of lung injury. However, there are no established methods that allow the three-dimensional visualization and quantification of pulmonary vascular permeability in vivo. Evans blue extravasation test and total protein test of bronchoalveolar lavage fluid (BALF) are permeability assays commonly used in research settings. However, they lack the ability to identify the spatial and temporal heterogeneity of endothelial barrier disruption, which is typical in lung injuries. Magnetic resonance (MR) and near-infrared (NIR) imaging have been proposed to image pulmonary permeability, but suffer from limited sensitivity and penetration depth, respectively. In this study, we report the first use of magnetic particle imaging (MPI) to assess pulmonary vascular leakage noninvasively in vivo in mice. A dextran-coated superparamagnetic iron oxide (SPIO), synomag®, was employed as the imaging tracer, and pulmonary SPIO extravasation was imaged and quantified to evaluate the vascular leakage. Animal models of acute lung injury and pulmonary fibrosis (PF) were used to validate the proposed method. MPI sensitively detected the SPIO extravasation in both acutely injured and fibrotic lungs in vivo, which was confirmed by ex vivo imaging and Prussian blue staining. Moreover, 3D MPI illustrated the spatial heterogeneity of vascular leakage, which correlated well with CT findings. Based on the in vivo 3D MPI images, we defined the SPIO extravasation index (SEI) to quantify the vascular leakage. A significant increase in SEI was observed in the injured lungs, in consistent with the results obtained via ex vivo permeability assays. Overall, our results demonstrate that 3D quantitative MPI serves as a useful tool to examine pulmonary vascular integrity in vivo, which shows promise for future clinical translation.

2.
Chemosphere ; 354: 141741, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38499071

RESUMO

In this study, an aerobic granular sludge electrochemical system (AGES) was established by applying the micro-electric field to an aerobic granular sludge (AGS) reactor for the degradation of sulfamethoxazole (SMZ). Under the stimulation of the micro-electric field, the granulation of sludge was improved and the degradation rate of SMZ was enhanced. The features of granular sludge were characterized by scanning electron microscopy and X-ray diffraction. The optimal degradation rate of SMZ (88%) was obtained at the voltage of 3 V and the effective electrode area of 800 mm2. The results of kinetics analyses revealed that the degradation of SMZ by AGES can be fitted with the second-order kinetic equation, showing a degradation rate constant (k) of 0.001 L mol-1·min-1. The degradation products of SMZ in the AGES system were detected by LC-MS and their possible degradation routes were elucidated. The micro-electric field in the AGES system played a selective role in microbes' enrichment and growth, changing the diversity of the microbial community. Pseudomonas, Tolumonas, and Acidovorax were the dominant bacteria in the AGES system, which is accountable for the abatement of SMZ and nutrients. This work provides a green means for improving AGS and paves the way for applying the AGS process to real-world wastewater treatment.


Assuntos
Microbiota , Esgotos , Esgotos/química , Eliminação de Resíduos Líquidos/métodos , Aerobiose , Reatores Biológicos , Nitrogênio
3.
Clin Neurol Neurosurg ; 239: 108226, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38484603

RESUMO

BACKGROUND AND PURPOSE: Studies on changes in the distal internal carotid artery based on high resolution magnetic resonance imaging (HRMRI) are scarce. Herein, we propose a histological classification system for patients with carotid artery pseudo-occlusion or occlusion based on preoperative HRMRI, for which we evaluated the feasibility and clinical implications. MATERIALS AND METHODS: From January 2017 to June 2021, 40 patients with Doppler ultrasound, CTA or MRA suggesting carotid artery occlusion were enrolled in this study. A new classification system based on HRMRI was established and subsequently verified by postoperative specimens. We recorded and analyzed patient characteristics, HRMRI data, recanalization rate, requirements of additional endovascular procedures, complications, and outcomes. RESULTS: Four histological classifications (type Ⅰ-Ⅳ) were identified. According to our classification system, 20 patients (50.00%) were type I, nine (22.50%) were type II, 7 (17.50%) were type III, and four (10.00%) were type Ⅳ. The success rate of recanalization was 88.89% (32/36) in type I-III patients. Four (44.44%) type Ⅱ patients and five (71.43%) type Ⅲ patients suffered from intraoperative dissection. CONCLUSION: Patients identified as types I (pseudo-occlusion) and II (thrombotic-occlusion) were able to be treated via hybrid revascularization with relatively low risk, while patients identified as type III (fibrous-occlusion) required more careful treatment. Recanalization is not suitable for patients identified as type Ⅳ. Our proposed classification system based on HRMRI data can be used as an adjunctive guide to predict the technical feasibility and success of revascularization via a hybrid technique.


Assuntos
Doenças das Artérias Carótidas , Estenose das Carótidas , Trombose , Humanos , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Estenose das Carótidas/complicações , Projetos Piloto , Estudos de Viabilidade , Artéria Carótida Interna/diagnóstico por imagem , Artéria Carótida Interna/cirurgia , Artéria Carótida Interna/patologia , Trombose/complicações , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/cirurgia , Doenças das Artérias Carótidas/complicações , Imageamento por Ressonância Magnética , Resultado do Tratamento , Estudos Retrospectivos
4.
Heliyon ; 10(6): e27450, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38524532

RESUMO

The inhalation of zinc chloride (ZnCl2) smoke is one of common resources of lung injury, potentially resulting in severe pulmonary complications and even mortality. The influence of ZnCl2 smoke on lysine succinylation (Ksucc) in the lungs remains uncertain. In this study, we used a ZnCl2 smoke inhalation mouse model to perform global proteomic and lysine succinylome analyses. A total of 6781 Ksucc sites were identified in the lungs, with injured lungs demonstrating a reduction to approximately 2000 Ksucc sites, and 91 proteins exhibiting at least five differences in the number of Ksucc sites. Quantitative analysis revealed variations in expression of 384 proteins and 749 Ksucc sites. The analysis of protein-protein interactions was conducted for proteins displaying differential expression and differentially expressed lysine succinylation. Notably, proteins with altered Ksucc exhibited increased connectivity compared with that in differentially expressed proteins. Beyond metabolic pathways, these highly connected proteins were also involved in lung injury-associated pathological reactions, including processes such as focal adhesion, adherens junction, and complement and coagulation cascades. Collectively, our findings contribute to the understanding of the molecular mechanisms underlaying ZnCl2 smoke-induced lung injury with a specific emphasis on lysine succinylation. These findings could pave the way for targeted interventions and therapeutic strategies to mitigate severe pulmonary complications and mortality associated with such injuries in humans.

5.
Environ Sci Pollut Res Int ; 31(11): 16497-16510, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38321275

RESUMO

In this study, nickel-cobalt co-modified stainless steel mesh (Ni-Co@SSM) was prepared and used as the biocathode in microbial electrolysis cell (MEC) for sulfamethazine (SMT) degradation. The optimal electrochemical performance of the Ni-Co@SSM was obtained at the electrodeposition time of 600 s, electrodeposition current density of 20 mA cm-2, and nickel-cobalt molar ratio of 1:2. The removal of SMT in MEC with the Ni-Co@SSM biocathode (MEC-Ni-Co@SSM) was 82%, which increased by 30% compared with the conventional anaerobic reactor. Thirteen intermediates were identified and the potential degradation pathways of SMT were proposed. Proteobacteria, Firmicutes, Patescibacteria, Chloroflexi, Bacteroidetes, and Euryarchaeota are the dominant bacteria at the phylum level in the MEC-Ni-Co@SSM, which are responsible for SMT metabolism. Due to the electrical stimulation, there was an increase in the abundance of the metabolic function and the genetic information processing. This work provides valuable insight into utilizing MECs for effective treatment of antibiotic-containing wastewater.


Assuntos
Níquel , Sulfametazina , Níquel/análise , Sulfametazina/metabolismo , Eletrodos , Eletrólise , Águas Residuárias , Bactérias/metabolismo
7.
Funct Integr Genomics ; 23(2): 84, 2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36930242

RESUMO

The growth of cancer, the effectiveness of treatment, and prognosis are all closely related to PANoptosis (include pyroptosis, apoptosis, and necroptosis). It remains unclear whether PANoptosis genes (PANGs) may contribute to lower-grade glioma (LGG) tumor microenvironment (TME). In this study, we collected 1203 LGG samples from three public databases and reported that PANoptosis involves TME interaction and prognosis. Firstly, we provided a comprehensive review of the pan-cancer landscape of PANGs in terms of expression characteristics, prognostic value, mutational profile, and pathway regulation. Then, we identified two distinct PANclusters, each with its own molecular, clinical, and immunological profile. We then developed a scoring system for LGG patients called PANscore. As well as investigating immune characteristics, tumor mutational characteristics, and drug sensitivity, we examined the differences between groups with high PANscores and those with low PANscores. Based on this PANscore and clinicopathological variables, an instant nomogram for predicting clinical survival in LGG patients was developed. Our thorough examination of PANGs in LGG revealed their probable function in TME, as well as their clinicopathological characteristics and prognosis. These discoveries could deepen our comprehension of PANGs in LGG and provide doctors fresh perspectives on how to forecast prognosis and create more efficient, individualized treatment plans.


Assuntos
Glioma , Microambiente Tumoral , Humanos , Microambiente Tumoral/genética , Glioma/genética , Apoptose , Mutação
8.
Nat Commun ; 14(1): 1311, 2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36899048

RESUMO

Mantle plumes have played a key role in tectonic events such as continental break-up and large magmatic events since at least the formation of Gondwana. However, as their signatures on Earth's surface, many of large igneous provinces have disappeared into the mantle during Earth's long-term evolution, meaning that plume remnants in the mantle are crucial in advancing mantle plume theory and accurately reconstructing Earth history. Here we present an electrical conductivity model for North Asia constructed from geomagnetic data. The model shows a large high-electrical-conductivity anomaly in the mantle transition zone beneath the Siberian Traps at the time of their eruption that we interpret to be a thermal anomaly with trace amounts of melt. This anomaly lies almost directly over an isolated low-seismic-wave-velocity anomaly known as the Perm anomaly. The spatial correlation of our anomaly with the Siberian Traps suggests that it represents a remnant of a superplume that was generated from the Perm anomaly. This plume was responsible for the late Permian Siberian large igneous province. The model strengthens the validity of the mantle plume hypothesis.

9.
Int J Hyg Environ Health ; 248: 114120, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36709744

RESUMO

OBJECTIVES: Droplets or aerosols loaded with SARS-CoV-2 can be released during breathing, coughing, or sneezing from COVID-19-infected persons. To investigate whether the most commonly applied air-cleaning device in dental clinics, the oral spray suction machine (OSSM), can provide protection to healthcare providers working in clinics against exposure to bioaerosols during dental treatment. METHOD: In this study, we measured and characterized the temporal and spatial variations in bioaerosol concentration and deposition with and without the use of the OSSM using an experimental design in a dental clinic setting. Serratia marcescens (a bacterium) and ΦX174 phage (a virus) were used as tracers. The air sampling points were sampled using an Anderson six-stage sampler, and the surface-deposition sampling points were sampled using the natural sedimentation method. The Computational Fluid Dynamics method was adopted to simulate and visualize the effect of the OSSM on the concentration spatial distribution. RESULTS: During dental treatment, the peak exposure concentration increased by up to 2-3 orders of magnitude (PFU/m3) for healthcare workers. Meanwhile, OSSM could lower the mean bioaerosol exposure concentration from 58.84 PFU/m3 to 4.10 PFU/m3 for a healthcare worker, thereby inhibiting droplet and airborne transmission. In terms of deposition, OSSM significantly reduced the bioaerosol surface concentration from 28.1 PFU/m3 to 2.5 PFU/m3 for a surface, effectively preventing fomite transmission. CONCLUSION: The use of OSSM showed the potential to restraint the spread of bioaerosols in clinical settings. Our study demonstrates that OSSM use in dental clinics can reduce the exposure concentrations of bioaerosols for healthcare workers during dental treatment and is beneficial for minimizing the risk of infectious diseases such as COVID-19.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Microbiologia do Ar , Aerossóis e Gotículas Respiratórios , Bactérias
10.
Materials (Basel) ; 15(21)2022 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-36363032

RESUMO

Under the condition of long-time high-temperature oxidation, oxidation in Al-Si coating will lead to degradation of the coating. To solve this problem, the Al-Si coating was treated before the oxidation experiment at different pre-oxidation temperatures and times. The structure, morphology and element distribution of the oxide film were characterized by XRD, SEM and EPMA, and the oxidation kinetics curves were drawn. The results show that the oxidation resistance of the pre-oxidized samples is improved in the process of constant temperature oxidation at 1000 °C. When the pre-oxidation temperature is set at 950 °C, the mass gain of the samples is the lowest, and the accelerated decomposition of Cr2O3 caused by high pre-oxidation temperature is avoided. After oxidation for 300 h, the oxide film on the surface is still continuous and dense without peeling. The samples pre-oxidized at 950 °C for 7 h show the best oxidation resistance in a 1000 °C constant temperature oxidation process, more α-Al2O3 oxides are generated on the coating surface and the element diffusion between the matrix and the coating caused by overly long oxidation time is avoided.

11.
Chemosphere ; 308(Pt 1): 136264, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36064014

RESUMO

Peroxymonosulfate (PMS)-based advanced oxidation process is considered a potential technology for water treatment. Here, palygorskite (PAL)-mediated cobalt-copper-ferrite nanoparticles (16%-CoCu0.4Fe1·6O4@PAL, donated as 16%-CCFO@PAL) were employed for PMS activation to remove bisphenol S (BPS). BPS degradation was greater than 99% under the optimal conditions within 25 min, on which the effects of various influencing factors were explored. The adsorption dissociation energy of PMS over 16%-CCFO@PAL was -6.27 eV, which was lower than that of the Cu-free catalyst (-6.15 eV), demonstrating the excellent catalytic ability of 16%-CCFO@PAL. The efficient catalytic ability of 16%-CCFO@PAL was also verified in real water samples. The oxidation intermediates were identified and their generations were systematically analyzed by DFT calculations. The possible degradation pathways of BPS were proposed and the toxicity of products was predicted. BPS affected the normal development of zebrafish embryos and the levels of sex hormone in adult male zebrafish, and was harmful to the tissues, such as testis, liver, and intestine of zebrafish. The 16%-CCFO@PAL/PMS process can effectively reduce the toxicity of BPS-polluted water. This study paves the way for the real application of 16%-CCFO@PAL/PMS oxidation process and provides a new perspective for the evaluation of water toxicity.


Assuntos
Nanopartículas , Poluentes Químicos da Água , Animais , Cobalto/toxicidade , Cobre/toxicidade , Compostos Férricos , Compostos de Magnésio , Masculino , Peróxidos , Fenóis , Compostos de Silício , Sulfonas , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade , Peixe-Zebra
12.
Build Environ ; 225: 109624, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36164582

RESUMO

Dental clinics have a potential risk of infection, particularly during the COVID-19 pandemic. Multi-compartment dental clinics are widely used in general hospitals and independent clinics. This study utilised computational fluid dynamics to investigate the bioaerosol distribution characteristics in a multi-compartment dental clinic through spatiotemporal distribution, working area time-varying concentrations, and key surface deposition. The infection probability of SARS-CoV-2 for the dental staff and patients was calculated using the Wells-Riley model. In addition, the accuracy of the numerical model was verified by field measurements of aerosol concentrations performed during a clinical ultrasonic scaling procedure. The results showed that bioaerosols were mainly distributed in the compartments where the patients were treated. The average infection probability was 3.8% for dental staff. The average deposition number per unit area of the treatment chair and table are 28729 pcs/m2 and 7945 pcs/m2, respectively, which creates a possible contact transmission risk. Moreover, there was a certain cross-infection risk in adjacent compartments, and the average infection probability for patients was 0.84%. The bioaerosol concentrations of the working area in each compartment 30 min post-treatment were reduced to 0.07% of those during treatment, and the infection probability was <0.05%. The results will contribute to an in-depth understanding of the infection risk in multi-compartment dental clinics, forming feasible suggestions for management to efficiently support epidemic prevention and control in dental clinics.

13.
J Hazard Mater ; 435: 128968, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35487000

RESUMO

Extensive studies revealed that Cl- could inhibit the removal of targeted pollutants under low Cl- conditions in the peroxymonosulfate (PMS) system. However, the enhanced effect of Cl- has always been overlooked under high Cl- conditions. Here, we find that high concentration of Cl- played a critical role in bisphenol S (BPS) degradation by activating PMS using 16%-CoFe2O4@PAL (16%-CFO@PAL). The removal of BPS was sharply enhanced after introducing 0.5 and 1.0 M Cl-, and the corresponding kobs increased to 0.922 min-1 and 1.103 min-1, which was 6-fold and 7-fold higher than the control (0.144 min-1), respectively. HOCl was demonstrated as the dominant species for removing BPS in 16%-CFO@PAL/PMS system under high Cl- circumstances. The typical chlorinated BPS intermediates were identified, which showed higher eco-toxicity than BPS. The chlorinated byproducts along with their toxicity could be effectively eliminated after 30 min. The possible formation mechanism of chlorinated products was further revealed by theoretical calculations. Toxicity assessment experiments showed that BPS significantly affected hormone levels of zebrafish and showed toxicity on the testis and liver of zebrafish, which could be reduced using 16%-CFO@PAL/PMS system. This study attracts attention to the overlooked HOCl in PMS-based processes under high salinity conditions.


Assuntos
Salinidade , Poluentes Químicos da Água , Animais , Peróxidos , Fenóis , Sulfonas , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade , Peixe-Zebra
14.
Front Physiol ; 13: 853956, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35370768

RESUMO

SLC26A10 is a member of the SLC26 gene family, but its role in insects is still unclear. We cloned the SLC26A10 gene of Nilaparvata lugens (NlSLC26A10) and found NlSLC26A10 contained 11 transmembrane regions and a STAS domain. Expression pattern analysis showed NlSLC26A10 expression was more upregulated in adults than in nymphs, highest in the ovary. After injection of double-stranded RNA (dsRNA) of NlSLC26A10, the mRNA level of NlSLC26A10 significantly decreased and, consequently, the ovarian development of adult females was hindered; the amount and the hatchability of eggs and yeast-like symbionts in mature oocytes decreased. Further study showed that NlSLC26A10 might result in decreased juvenile hormone level and vitellogenin expression. These results indicate that NlSLC26A10 plays an essential role in the reproduction of N. lugens.

15.
Insects ; 13(3)2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35323600

RESUMO

The brown planthopper, Nilaparvata lugens, is a difficult-to-control insect pest affecting rice yields in Asia. As a structural component of the inter-alpha-trypsin inhibitor (ITI), the inter-alpha-trypsin inhibitor heavy chain (ITIH) has been reported to be involved in various inflammatory or malignant disorders, ovarian development, and ovulation. To reveal the function of ITIH4 in N. lugens, the gene encoding N. lugens ITIH4 (NlITIH4) was cloned and characterized. NlITIH4 contains a signal peptide, a vault protein inter-alpha-trypsin domain, and a von Willebrand factor type A domain. qPCR analysis showed that NlITIH4 was expressed at all developmental stages and in all tissues (fat body, ovary, and gut), with the highest expression in the fat body. Double stranded NlITIH4 (dsNlITIH4) injection clearly led to an RNAi-mediated inhibition of the expression of NlITIH4 and resulted in reduced survival, delayed ovarian development, and reduced egg production and egg hatching. These results indicate that NlITIH4 plays an important role in the development and reproduction of N. lugens.

16.
J Oncol ; 2022: 8361775, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35356252

RESUMO

Objective: To investigate the efficiency of capecitabine (CAP) plus temozolomide (TEM) in refractory pituitary adenoma after tumor resection and its impact on serum prolactin (PRL), insulin-like growth factor 1 (IGF-1), and growth hormone (GH) levels. Methods: From January 2017 to January 2020, 80 patients assessed for eligibility receiving transsphenoidal tumor resection for refractory pituitary adenoma in the Department of Neurosurgery of our hospital were recruited. They were randomly distributed at a ratio of 1 : 1 via the random number table method to receive either bromocriptine and TEM (control group) or bromocriptine plus combination chemotherapy of TEM and CAP (study group). The two groups were compared in terms of clinical efficacy and serum levels of PRL, IGF-1, and GH. Results: The objective response rate (ORR) was 87.50% and 67.50% in the study group and the control group, respectively (P=0.032). Before treatment, two groups had similar levels of PRL, IGF-1, and GH. After treatment, PRL levels in the study group were lower than that in the control group (278.35 ± 39.25 versus 326.35 ± 42.45, P < 0.001). Compared with the control group, IGF-1 levels in the study group were also lower (311.78 ± 28.82 versus 364.35 ± 31.35, P < 0.001). The study group presented markedly lower levels of thyroid-stimulating hormone (TSH) and higher serum levels of free thyroxine-4 (FT-4) and adrenocorticotropic hormone (ACTH) versus the control group (P < 0.05). The incidence of adverse events was comparable between the study group (30.0%) and the control group (22.5%) (P > 0.05). All eligible patients had similar progression-free survival (PFS) after chemotherapy. Conclusion: For patients with refractory pituitary adenoma, the combination chemotherapy of CAP and TEM significantly improves clinical outcomes and corrects hormonal disturbances, with a good safety profile, but its long-term efficacy requires further investigation.

17.
J Hazard Mater ; 432: 128757, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35344892

RESUMO

Novel nitrogen (N)-doped cellulose biochar (NC1000-10) with large adsorption capacity (103.59 mg g-1) for atrazine (ATZ) was synthesized through the one-pot method. It has the best adsorption efficiency than N-doped biochars prepared from hemicellulose and lignin. The adsorption behaviors of ATZ by N-doped biochars with different N doping ratios (NC1000-5, NC1000-10, NC1000-20 and NC1000-30) were significantly different, which was attributed to the difference of sp2 conjugate C (ID/IG = 0.99-1.18) and doped heteroatom N (pyridinic N, pyrrolic N and graphitic N). Adsorption performance of ATZ on NC1000-10 conformed to the pseudo-second-order kinetic and Langmuir adsorption isotherm model. Thermodynamic calculations showed that adsorption performance was favorable. Besides, wide pH adaptability (pH = 2-10), good resistance to ionic strength and excellent recycling efficiency make it have extensive practical application potential. Further material characterizations and the density functional theory (DFT) calculations indicated that good adsorption performance of NC1000-10 for ATZ mainly depended on chemisorption, and π-π electron donor-acceptor (EDA) interaction contributed the most due to high graphitization degree. Specifically, pyridinic N and graphitic N further promoted adsorption performance by hydrophobic effect and π-π EDA interaction between ATZ and NC1000-10, respectively. Pyrrolic N and other surface functional groups (-COOH, -OH) facilitated the hydrogen bond effect.


Assuntos
Atrazina , Poluentes Químicos da Água , Adsorção , Carvão Vegetal/química , Elétrons , Cinética , Oxidantes , Poluentes Químicos da Água/análise
18.
J Mol Cell Biol ; 14(3)2022 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35259279

RESUMO

Sense mutations in several conserved modifiable sites of histone H3 have been found to be strongly correlated with multiple tissue-specific clinical cancers. These clinical site mutants acquire a distinctively new epigenetic role and mediate cancer evolution. In this study, we mimicked histone H3 at the 56th lysine (H3K56) mutant incorporation in mouse embryonic stem cells (mESCs) by lentivirus-mediated ectopic expression and analyzed the effects on replication and epigenetic regulation. The data show that two types of H3K56 mutants, namely H3 lysine 56-to-methionine (H3K56M) and H3 lysine 56-to-alanine (H3K56A), promote replication by recruiting more minichromosome maintenance complex component 3 and checkpoint kinase 1 onto chromatin compared with wild-type histone H3 and other site substitution mutants. Under this condition, the frequency of genomic copy number gain in H3K56M and H3K56A cells globally increases, especially in the Mycl1 region, a known molecular marker frequently occurring in multiple malignant cancers. Additionally, we found the disruption of H3K56 acetylation distribution in the copy-gain regions, which indicates a probable epigenetic mechanism of H3K56M and H3K56A. We then identified that H3K56M and H3K56A can trigger a potential adaptation to transcription; genes involved in the mitogen-activated protein kinase pathway are partially upregulated, whereas genes associated with intrinsic apoptotic function show obvious downregulation. The final outcome of ectopic H3K56M and H3K56A incorporation in mESCs is an enhanced ability to form carcinomas. This work indicates that H3K56 site conservation and proper modification play important roles in harmonizing the function of the replication machinery in mESCs.


Assuntos
Histonas , Lisina , Acetilação , Animais , Epigênese Genética , Histonas/metabolismo , Lisina/metabolismo , Camundongos , Células-Tronco Embrionárias Murinas/metabolismo
19.
Aging (Albany NY) ; 13(21): 24339-24348, 2021 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-34775378

RESUMO

In the present study, we found the expression of miR-15a-5p (miR-15a) was increased in glioma tissues, and we further explore the underlying mechanism of miR-15a in glioma progression. Microarray analysis used to identify the differentially expressed microRNAs (miRNAs) in glioma tissues. The expression of miR-15a in glioma tissues and cell lines was tested by qRT-PCR. Luciferase assay was used to determine the binding between miR-15a and Smad7. Wound healing and transwell assay were used to examine the role of miR-15a/Smad7 in SHG139 cells. Western blot was used to detect the protein level of Smad7 and epithelial-mesenchymal transition (EMT) markers. A tumor formation model in nude mice was established to measure the role of miR-15a in vivo. MiR-15a was significantly increased in glioma tissues and cells, which indicated a poor prognosis of glioma patients. MiR-15a mimics induced miR-15a level in SHG139 cells, and promoted the malignancy of SHG139 cells, while miR-15a inhibitor showed the opposite effects. Luciferase assay indicated that Smad7 was the direct target of miR-15a, and Smad7 was down-regulated in glioma tissues. Functional experiments revealed that miR-15a inhibitor inhibited the EMT pathway and the migration and invasion of glioma cells, but the silencing of Smad7 reversed the effects of miR-15a inhibitor in EMT pathway and glioma progression. Finally, we performed animal experiments to verify the role of miR-15a in vivo. Present study showed that deletion of miR-15a inhibited the activation of EMT signaling via targeting Smad7, thus suppressed the tumorigenesis and tumor growth of glioma.


Assuntos
Transição Epitelial-Mesenquimal/genética , Glioma , MicroRNAs/genética , Proteína Smad7/genética , Animais , Linhagem Celular Tumoral , Inativação Gênica , Glioma/genética , Glioma/metabolismo , Glioma/patologia , Humanos , Masculino , Camundongos , Camundongos Nus
20.
Aging (Albany NY) ; 13(17): 21122-21133, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34520391

RESUMO

Glioma is a prevalent brain malignancy with aggressive progression and with grave prognosis in adults. Circular RNAs have been reported to regulate glioma development and function as the diagnostic, prognostic, and therapeutic biomarkers. In this study, we were interested the function of circular RNA ZNF609 in modulating glioma. Remarkably, knockdown of ZNF609 by siRNA in glioma cells reduced cell viabilities and Edu-positive. The silencing of ZNF609 stimulated the apoptosis of glioma cells. Meanwhile, the ZNF609 depletion inhibited the invasion and migration of glioma cells. In glioma cells, the mRNA and protein expression of E-cadherin was enhanced, while Vimentin was reduced by the inhibition of ZNF609. The glucose uptake, lactate product, and ATP production in glioma cells were suppressed by ZNF609 knockdown. Mechanically, miR-378b was sponged by ZNF609 and targeted SLC2A1 in glioma cells. ZNF609 enhanced SLC2A1 expression by inhibiting miR-378b. The inhibition of miR-378b or the enhancement of SLC2A1 reversed ZNF609 depletion-regulated glioma cell proliferation in vitro. The depletion of ZNF609 suppressed glioma cell growth in the nude mice. Therefore, we concluded that ZNF609 contributed to cell survival and glycolysis of glioma by targeting miR-378b/SLC2A1 axis. ZNF609 and miR-378b may function as potential treatment targets in glioma.


Assuntos
Glioma/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Glicólise/fisiologia , MicroRNAs/metabolismo , RNA Circular/metabolismo , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Sistemas de Liberação de Medicamentos , Transportador de Glucose Tipo 1/genética , Humanos , MicroRNAs/genética , Mimetismo Molecular , Invasividade Neoplásica , Interferência de RNA , RNA Circular/genética , RNA Interferente Pequeno
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