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1.
Neural Regen Res ; 18(3): 603-608, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36018184

RESUMO

ß2-Microglobulin (ß2M), a component of the major histocompatibility complex class I molecule, is associated with aging-related cognitive impairment and Alzheimer's disease. Although upregulation of ß2M is considered to be highly related to ischemic stroke, the specific role and underlying mechanistic action of ß2M are poorly understood. In this study, we established a rat model of focal cerebral ischemia by occlusion of the middle cerebral artery. We found that ß2M levels in the cerebral spinal fluid, serum, and brain tissue were significantly increased in the acute period but gradually decreased during the recovery period. RNA interference was used to inhibit ß2M expression in the acute period of cerebral stroke. Tissue staining with 2,3,5-triphenyltetrazolium chloride and evaluation of cognitive function using the Morris water maze test demonstrated that decreased ß2M expression in the ischemic penumbra reduced infarct volume and alleviated cognitive deficits, respectively. Notably, glial cell, caspase-1 (p20), and Nod-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation as well as production of the inflammatory cytokines interleukin-1ß, interleukin-6, and tumor necrosis factor-α were also effectively inhibited by ß2M silencing. These findings suggest that ß2M participates in brain injury and cognitive impairment in a rat model of ischemic stroke through activation of neuroinflammation associated with the NLRP3 inflammasome.

2.
Huan Jing Ke Xue ; 43(11): 4931-4938, 2022 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-36437065

RESUMO

Microplastics widely exist in various environmental media and have become a global environmental problem. To investigate the pollution characteristics, deposition patterns, and influencing factors of microplastics in the sediments of bay beach, five typical beaches were selected in Xiamen Bay. According to the tidal variation, 0-10 cm, 10-20 cm, and 20-30 cm sediment column samples were collected in layers at the high tide line, middle tide line, and low tide line at the same time, and the characteristics of the horizontal and vertical distribution of microplastics in the beach sediments were studied. The results showed that the abundance of microplastics in 45 sediment samples in Xiamen Bay beach ranged from 39 to 260 n·kg-1, with an average abundance of (114±26) n·kg-1. The shapes of microplastics were mainly fibers, fragments, granules, and foams, with fibers making up the largest proportion. The main components were polyethylene terephthalate (PET), cellophane, and polyethylene (PE). The colors of microplastics included transparent, yellow, blue, black, white, etc. The average abundance of microplastics showed a certain pattern depending on the beach location, intertidal zone, and sampling depth. Moreover, the abundance and distribution of microplastics on the beach were affected by various natural and human factors such as waves, tides, shoreline shape, the number of tourists, and the cleaning of marine floating debris. These results aid the understanding of the distribution characteristics and sources of microplastics in beach sediments, provide a basis for the transport of microplastics from land to sea, and provide data support for the collection of sea floating garbage and shoreline garbage.


Assuntos
Microplásticos , Poluentes Químicos da Água , Humanos , Plásticos , Sedimentos Geológicos , Baías , Monitoramento Ambiental/métodos , Poluentes Químicos da Água/análise
3.
ACS Nano ; 16(11): 19363-19372, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36350673

RESUMO

Electroporation (EP) is an effective and widely accepted intracellular delivery method for fundamental research and medical applications. Existing electroporation methods usually require a commercially available EP system or tailor-made high-voltage (HV, up to kV) power source and are complicated, expensive, harmful to the cells, and even dangerous to the operators. A triboelectric nanogenerator (TENG) is a highly studied device that can generate HV output with limited charges and ultrahigh internal impedance. Here, we developed a Bulk Electroporation System based on TENG (BEST). To maximize the load voltage of the TENG, a flowing EP unit with a capillary was designed as a resistive load to realize impedance matching. A low conductivity buffer was used to further match and assist cell electroporation. Besides, the electrical model and experiments on cells transfected with the BEST showed that the bulk electric field of the cell medium could reach up to 1 kV/cm, therefore resulting in a nearly 30 times increase of trans-membrane potential, thus largely improving transfection efficiency. Finally, using 40 kDa FITC-dextran, we showed that a delivery efficiency above 50% with a cell viability maintained over 90% can be achieved in HeLa cells. This work demonstrated the potential of TENG in the biomedical field as a naturally safe HV power source. It also provided a simple, alternative, and low-cost solution for EP research and related biomedicine applications.


Assuntos
Fontes de Energia Elétrica , Eletroporação , Humanos , Células HeLa , Transfecção , Eletricidade
4.
Dalton Trans ; 51(45): 17361-17367, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36322012

RESUMO

Designing highly active and durable oxygen evolution reaction (OER) electrocatalysts is indispensable for promoting the sluggish reaction kinetics of OER to achieve low overpotential. RuO2 is one of the representative oxygen evolution electrocatalysts in acid electrolytes, but it still faces the problem of poor stability. Herein, RuO2 nanocrystal with an ultra-small size of approximately 3.5 nm loaded on N-doped hierarchical porous carbon (NHC) is successfully synthesized by RuCl3 dipping, followed by an annealing process. It is found that NHC is assembled of porous nanosheets with a high specific surface area (BET up to 2107 m2 g-1), which could provide more active sites for RuO2 loading and enable decorated catalysts to be effectively utilized. Combining the advantages of porous NHC and the high electrocatalytic activity of RuO2, the optimized electrocatalyst RuO2/NHC3 achieves a low overpotential of 186 mV at 10 mA cm-2 for acidic water oxidation with a Tafel slope as low as 60 mV dec-1 and maintains excellent long-term stability throughout the 27 h chronopotentiometry test in 0.5 M H2SO4. The elevated acidic OER activity and stability can be attributed to the diminutive size, abundant oxygen vacancies, and enlarged electrochemically active surface area of RuO2/NHC3. This work could provide opportunities to explore efficient anodic electrocatalysts in acidic media.

5.
J Am Heart Assoc ; 11(21): e026174, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36314496

RESUMO

Background Restenosis is one of the main bottlenecks in restricting the further development of cardiovascular interventional therapy. New signaling molecules involved in the progress have continuously been discovered; however, the specific molecular mechanisms remain unclear. MTMR14 (myotubularin-related protein 14) is a novel phosphoinositide phosphatase that has a variety of biological functions and is involved in diverse biological processes. However, the role of MTMR14 in vascular biology remains unclear. Herein, we addressed the role of MTMR14 in neointima formation and vascular smooth muscle cell (VSMC) proliferation after vessel injury. Methods and Results Vessel injury models were established using SMC-specific conditional MTMR14-knockout and -transgenic mice. Neointima formation was assessed by histopathological methods, and VSMC proliferation and migration were assessed using fluorescence ubiquitination-based cell cycle indicator, transwell, and scratch wound assay. Neointima formation and the expression of MTMR14 was increased after injury. MTMR14 deficiency accelerated neointima formation and promoted VSMC proliferation after injury, whereas MTMR14 overexpression remarkably attenuated this process. Mechanistically, we demonstrated that MTMR14 suppressed the activation of PLK1 (polo-like kinase 1) by interacting with it, which further leads to the inhibition of the activation of MEK/ERK/AKT (mitogen-activated protein kinase kinase/extracellular-signal-regulated kinase/protein kinase B), thereby inhibiting the proliferation of VSMC from the medial to the intima and thus preventing neointima formation. Conclusions MTMR14 prevents neointima formation and VSMC proliferation by inhibiting PLK1. Our findings reveal that MTMR14 serves as an inhibitor of VSMC proliferation and establish a link between MTMR14 and PLK1 in regulating VSMC proliferation. MTMR14 may become a novel potential therapeutic target in the treatment of restenosis.


Assuntos
Monoéster Fosfórico Hidrolases , Proteínas Serina-Treonina Quinases , Lesões do Sistema Vascular , Animais , Camundongos , Movimento Celular , Proliferação de Células , Células Cultivadas , Camundongos Transgênicos , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Neointima/patologia , Monoéster Fosfórico Hidrolases/metabolismo , Lesões do Sistema Vascular/genética , Lesões do Sistema Vascular/prevenção & controle , Lesões do Sistema Vascular/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo
6.
Int J Biochem Cell Biol ; 152: 106308, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36174923

RESUMO

Deletion of the Schizosaccharomyces pombe pentatricopeptide repeat gene ppr10 severely impairs mitochondrial translation, resulting in defective oxidative phosphorylation (OXPHOS). ppr10 deletion also induces iron starvation response, resulting in increased reactive oxygen species (ROS) production and reduced viability under fermentative conditions. S. pombe has two principal stress-response pathways, which are mediated by the mitogen-activated protein kinase Sty1 and the basic leucine zipper transcription factor Pap1, respectively. In this study, we examined the roles of Sty1 and Pap1 in the cellular response to the mitochondrial translation defect caused by ppr10 deletion. We found that ppr10 deletion resulted in two waves of stress protein activation. The early response occurred in exponential phase and resulted in the expression of a subset of stress proteins including Gst2 and Obr1. The upregulation of some of these stress proteins in Δppr10 cells in early response is dependent on the basal nuclear levels of Sty1 or Pap1. The late response occurred in early stationary phase and coincided with the stable localization of Sty1 and Pap1 in the nucleus, presumably resulting in persistent activation of a large set of stress proteins. Deletion of sty1 in Δppr10 cells caused severe defects in cell division and growth, and further impaired cell viability. Deletion of the mitochondrial superoxide dismutase gene sod2 whose expression is controlled by Sty1 severely inhibited the growth of Δppr10 cells. Overexpression of sod2 improves the viability of Δppr10 cells. Our results support an important role for Sty1 in counteracting stress induced by ppr10 deletion under fermentative growth conditions.

7.
J Affect Disord ; 319: 244-251, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36162654

RESUMO

BACKGROUND/AIM: There is growing awareness that specific childhood trauma (CT) may confer to the unique risk of depression, but little is known about this. The present study seeks to provide insight into how CT subtypes may impact distinct depressive symptoms over time based on the dimensional model of adversity (DMA). METHODS: A total of 3535 college freshmen participated in a 2-year, four waves longitudinal tracking study. A conditional parallel latent growth curve model (LGCM) was constructed to examine the impacts of different types of CT (threat and deprivation) on the development of depressed mood and anhedonia, and whether these relationships vary across gender. RESULTS: Our findings revealed that threat and deprivation could differentially relate to depressed mood and anhedonia. Both threat and deprivation predicted initial depressed mood levels (ß = 0.309, p < 0.001; ß = 0.175, p < 0.001, respectively) and its trajectory (ß = -0.139, p = 0.068; ß = -0.168, p < 0.05, respectively). Only deprivation predicted anhedonia levels (ß = 0.318, p < 0.001) and trajectory (ß = -0.218, p < 0.001). This pattern of relationships between CT and depressive symptoms varied across gender. CONCLUSION: These findings highlight specific pathways and symptomatic manifestations of the impacts of different CT subtypes on depression and are consistent with the hypothesis of DMA. Threat and deprivation predicted more severe depressed mood, whereas deprivation uniquely conferred to the risk of depression via elevated anhedonia. Meanwhile, the deleterious effects of CT would persist during early adulthood. Gender differences were also discussed.


Assuntos
Experiências Adversas da Infância , Transtorno Depressivo , Humanos , Adulto , Anedonia , Depressão/epidemiologia , Depressão/diagnóstico , Estudos Longitudinais
8.
Chem Commun (Camb) ; 58(72): 10088-10090, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-35997034

RESUMO

Herein, choline chloride (CC) is adopted as an additive in an aqueous ZnCl2 electrolyte to enhance the electrochemical stability of zinc plating/stripping. The choline cation can be adsorbed on the zinc anode surface to inhibit the zinc dendrite growth. Meanwhile, the -OH group can disrupt the initial hydrogen bond networks in the electrolyte, which can alleviate the water-induced side reactions. As a result, the Zn||Zn symmetric cell stably cycles for over 1700 h (1.0 mA cm-2, 0.5 mA h cm-2).


Assuntos
Colina , Zinco , Eletrólitos
9.
Cell Biochem Biophys ; 80(4): 723-735, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35994220

RESUMO

Malignant glioma, especially glioblastoma (GBM), has historically been associated with a low survival rate. The hyperactivation of STAT3 played a key role in GBM initiation and resistance to therapy; thus, there is an urgent requirement for novel STAT3 inhibitors. BP-1-102 was recently reported as a biochemical inhibitor of STAT3, but its roles and mechanism in biological behavior of glioma cells were still unclear. In this study, the effects of BP-1-102 on proliferation, apoptosis, invasion and neurosphere formation of glioma cell were investigated. Our results indicated that BP-1-102 inhibited the proliferation of U251 and A172 cells, and their IC50 values were 10.51 and 8.534 µM, respectively. Furthermore, BP-1-102 inhibited the invasion and migration abilities of U251 and A172 cells by decreasing the expression of matrix metallopeptidase 9, and induced glioma cell apoptosis by decreasing the expression of B-cell lymphoma-2. BP-1-102 also inhibited the formation of neurosphere. Mechanically, BP-1-102 reduced the phosphorylation of STAT3 and the p-STAT3's nuclear translocation in glioma cells. Thus, this study herein provided a potential drug for glioma therapy.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Ácidos Aminossalicílicos , Apoptose , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Glioma/metabolismo , Humanos , Metaloproteases/metabolismo , Metaloproteases/farmacologia , Invasividade Neoplásica/prevenção & controle , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fator de Transcrição STAT3/metabolismo , Sulfonamidas
10.
Food Chem Toxicol ; 168: 113321, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35931247

RESUMO

Vitamin C (VC), in regard to its effectiveness against tumors, has had a controversial history in cancer treatment. However, the anticancer mechanisms of VC are not fully understood. Here, we reported that VC exerted an anticancer effect on cancer cell and xenograft models via inhibiting HIF-1α-dependent cell proliferation and promoting p53-dependent cell apoptosis. To be specific, VC modulated the competitive binding of HIF-1α and p53 to their common E3 ubiquitin ligase CBL, thereby inhibiting tumorigenesis. Moreover, VC treatment activated SIRT1, resulting in p53 deacetylation and CBL-p53 complex dissociation, which in turn facilitated CBL recruitment of HIF-1α for ubiquitination in a proteasome-dependent manner. Altogether, our results provided a mechanistic rationale for exploring the therapeutic use of VC in cancer therapy.


Assuntos
Neoplasias da Mama , Ubiquitina-Proteína Ligases , Ácido Ascórbico/farmacologia , Ligação Competitiva , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Sirtuína 1/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
11.
Molecules ; 27(14)2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35889210

RESUMO

Breast cancer is one of the leading causes of death worldwide, and synthetic chemicals targeting specific proteins or various molecular pathways for tumor suppression, such as ERK inhibitors and degraders, have been intensively investigated. The targets of ERK participate in the regulation of critical cellular mechanisms and underpin the progression of anticancer therapy. In this study, we identified a novel small molecule, which we named Z734, as a new mitogen-activated protein kinase 1 (ERK2) degrader and demonstrated that Z734 inhibits cell growth by inducing p53-mediated apoptotic pathways in human breast cancer cells. Treatment with Z734 resulted in the inhibition of cancer cell proliferation, colony formation and migration invasion, as well as cancer cell death via apoptosis. In addition, the Co-IP and GST pulldown assays indicated that the HECT and RLD domains containing E3 ubiquitin protein ligase 3 (HERC3) could directly interact with ERK2 through the HECT domain, promoting ERK2 ubiquitination. We also observed a strong link between HERC3 and p53 for the modulation of apoptosis. HERC3 can increase the protein and phosphorylation levels of p53, which further promotes apoptotic activity. In a xenograft mouse model, the effect was obtained in a treatment group that combined Z734 with lapatinib compared with that of the single-treatment groups. In summary, our results indicated that Z734 actively controls the development of breast cancer through apoptosis, and HERC3 may mediate ERK2 and p53 signaling, which offers new potential targets for clinical therapy.


Assuntos
Neoplasias da Mama , Proteína Quinase 1 Ativada por Mitógeno , Animais , Apoptose , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Células MCF-7 , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Fosforilação , Transdução de Sinais , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
12.
Zhongguo Zhong Yao Za Zhi ; 47(14): 3718-3722, 2022 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-35850828

RESUMO

Traditional Chinese medicine(TCM) has its unique understanding of the etiology, pathogenesis, and risk factors of di-seases, and is advantageous in the study of risk prognosis.First recorded in Huangdi's Internal Classic, the TCM theory of treating di-sease before its onset has a long history.Supplemented and improved by the later generations of doctors, the TCM theory of treating di-sease before its onset has been applied to clinical practice and achieved good results.With the development of modern medicine, it has become a new trend to construct the risk prediction model integrating the research results of modern medicine with disease and syndrome combination of TCM characteristics.The construction of risk prediction model of disease and syndrome combination is conducive to early clinical screening and intervention, and provides ideas for the integration of TCM and western medicine.Coronary heart disease(CHD) is one of the common chronic diseases, and percutaneous coronary intervention(PCI) is an important therapeutic approach.In-stent restenosis(ISR) is a common complication after PCI, which seriously affects the outcome and prognosis of patients.Although some patients can be treated with balloon dilatation and endovascular stents, a significant number of patients still refuse secondary stenting intervention.The construction of risk prediction model of disease and syndrome combination for ISR after PCI can provide an effective tool for clinical risk prediction of ISR and indicators with TCM characteristics for early screening and intervention of people at a high risk of ISR, and guide clinical monitoring and intervention, which has certain clinical significance and reference value for the prevention and reduction of ISR.


Assuntos
Reestenose Coronária , Intervenção Coronária Percutânea , Reestenose Coronária/etiologia , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Fatores de Risco , Stents/efeitos adversos , Resultado do Tratamento
13.
J Appl Microbiol ; 133(5): 2790-2801, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35870153

RESUMO

AIMS: Phenazines, such as phenazine-1-carboxylic acid (PCA), phenazine-1-carboxamide (PCN), 2-hydroxyphenazine-1-carboxylic acid (2-OH-PCA), 2-hydroxyphenazine (2-OH-PHZ), are a class of secondary metabolites secreted by plant-beneficial Pseudomonas. Ps. chlororaphis GP72 utilizes glycerol to synthesize PCA, 2-OH-PCA and 2-OH-PHZ, exhibiting broad-spectrum antifungal activity. Previous studies showed that the addition of dithiothreitol (DTT) could increase the phenazines production in Ps. chlororaphis GP72AN. However, the mechanism of high yield of phenazine by adding DTT is still unclear. METHODS AND RESULTS: In this study, untargeted and targeted metabolomic analysis were adopted to determine the content of metabolites. The results showed that the addition of DTT to GP72AN affected the content of metabolites of central carbon metabolism, shikimate pathway and phenazine competitive pathway. Transcriptome analysis was conducted to investigate the changed cellular process, and the result indicated that the addition of DTT affected the expression of genes involved in phenazine biosynthetic cluster and genes involved in phenazine competitive pathway, driving more carbon flux into phenazine biosynthetic pathway. Furthermore, genes involved in antioxidative stress, phosphate transport system and mexGHI-opmD efflux pump were also affected by adding DTT. CONCLUSION: This study demonstrated that the addition of DTT altered the expression of genes related to phenazine biosynthesis, resulting in the change of metabolites involved in central carbon metabolism, shikimate pathway and phenazine competitive pathway. SIGNIFICANCE AND IMPACT OF THE STUDY: This work expands the understanding of high yield of phenazine by the addition of DTT and provides several targets for increasing phenazine production.


Assuntos
Pseudomonas chlororaphis , Pseudomonas chlororaphis/genética , Pseudomonas chlororaphis/metabolismo , Glicerol/metabolismo , Antifúngicos/metabolismo , Ditiotreitol/metabolismo , Transcriptoma , Fenazinas/metabolismo , Metabolômica , Perfilação da Expressão Gênica , Carbono/metabolismo , Fosfatos/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo
14.
Sci Data ; 9(1): 312, 2022 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-35710683

RESUMO

With the rapid development of high-throughput sequencing technology, the amount of metagenomic data (including both 16S and whole-genome sequencing data) in public repositories is increasing exponentially. However, owing to the large and decentralized nature of the data, it is still difficult for users to mine, compare, and analyze the data. The animal metagenome database (AnimalMetagenome DB) integrates metagenomic sequencing data with host information, making it easier for users to find data of interest. The AnimalMetagenome DB is designed to contain all public metagenomic data from animals, and the data are divided into domestic and wild animal categories. Users can browse, search, and download animal metagenomic data of interest based on different attributes of the metadata such as animal species, sample site, study purpose, and DNA extraction method. The AnimalMetagenome DB version 1.0 includes metadata for 82,097 metagenomes from 4 domestic animals (pigs, bovines, horses, and sheep) and 540 wild animals. These metagenomes cover 15 years of experiments, 73 countries, 1,044 studies, 63,214 amplicon sequencing data, and 10,672 whole genome sequencing data. All data in the database are hosted and available in figshare https://doi.org/10.6084/m9.figshare.19728619 .


Assuntos
Bases de Dados Factuais , Metagenoma , Animais , Bovinos , Sequenciamento de Nucleotídeos em Larga Escala , Cavalos , Metadados , Metagenômica , Ovinos , Suínos
15.
Oxid Med Cell Longev ; 2022: 9469143, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35528518

RESUMO

Background: Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2), a novel immunoregulatory protein, has been reported to regulate inflammation and apoptosis. The role of TIPE2 in cardiovascular disease, especially cardiac hypertrophy, has not been elucidated. Thus, the aim of the present study was to explore the role of TIPE2 in cardiac hypertrophy. Methods: Mice were subjected to aortic banding (AB) to induce an adverse hypertrophic model. To overexpress TIPE2, mice were injected with a lentiviral vector expressing TIPE2. Echocardiographic and hemodynamic analyses were used to evaluate cardiac function. Neonatal rat cardiomyocytes (NRCMs) and mouse peritoneal macrophages (MPMs) were isolated and stimulated with angiotensin II. NRCMs and MPM were also cocultured and stimulated with angiotensin II. Cells were transfected with Lenti-TIPE2 to overexpress TIPE2. Results: TIPE2 expression levels were downregulated in hypertrophic mouse hearts and in macrophages in heart tissue. TIPE2 overexpression attenuated pressure overload-induced cardiac hypertrophy, fibrosis, and cardiac dysfunction. Moreover, we found that TIPE2 overexpression in neonatal cardiomyocytes did not relieve the angiotensin II-induced hypertrophic response in vitro. Furthermore, TIPE2 overexpression downregulated TLR4 and NF-κB signaling in macrophages but not in cardiomyocytes, which led to diminished inflammation in macrophages and consequently reduced the activation of hypertrophic Akt signaling in cardiomyocytes. TLR4 inhibition by TAK-242 did not enhance the antihypertrophic effect of TIPE2 overexpression. Conclusions: The present study indicated that TIPE2 represses macrophage activation by targeting TLR4, subsequently inhibiting cardiac hypertrophy.


Assuntos
Receptor 4 Toll-Like , Fator de Necrose Tumoral alfa , Angiotensina II/metabolismo , Angiotensina II/farmacologia , Animais , Cardiomegalia/patologia , Modelos Animais de Doenças , Inflamação/patologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Ratos , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
16.
Eur J Med Chem ; 238: 114446, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35597008

RESUMO

AlkB homolog 5 (ALKBH5) is an RNA m6A demethylase involved in the regulation of genes transcription, translation and metabolism and has been considered as a promising therapeutic target for various human diseases, especially cancers. However, there is still a lack of potent and selective ALKBH5 inhibitors. Herein, we report a new class of ALKBH5 inhibitors containing the 1-aryl-1H-pyrazole scaffold, which were obtained through fluorescence polarization-based screening, structural optimization and structure-activity relationship analysis. Among these compounds, 20m was the most potent one, which showed an IC50 value of 0.021 µM in fluorescence polarization assay. Compound 20m exhibited high selectivity towards ALKBH5 versus FTO as well as other AlkB subfamily members, indicating good selectivity for ALKBH5. Cellular thermal shift assay (CETSA) analysis showed that 20m could efficiently stabilize ALKBH5 in HepG2 cells. Dot blot assay demonstrated that 20m could increase m6A level in intact cells. Collectively, 20m is a potent, selective and cell active ALKBH5 inhibitor and could be used as a versatile chemical probe to explore the biological function of ALKBH5.


Assuntos
Homólogo AlkB 5 da RNA Desmetilase , RNA , Homólogo AlkB 5 da RNA Desmetilase/química , Homólogo AlkB 5 da RNA Desmetilase/metabolismo , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Humanos , RNA/química , Relação Estrutura-Atividade
17.
Sci Total Environ ; 837: 155887, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35568176

RESUMO

Air temperature (Ta) data obtained from meteorological stations were spatially discontinuous. Some satellite data have complete spatial coverage and strong relationships with Ta (e.g., elevation and land surface temperature). Therefore, Ta can be mapped using in situ Ta and satellite data. However, this method may have a large bias when estimating the extreme Ta. In this study, the error prediction and correction (EPC) method, incorporating Cubist machine learning algorithm, was proposed to improve the estimation of extreme Ta. The accuracy of the EPC method was compared with that of the widely used method in previous studies in east China from 2003 to 2012. The mean absolute errors (MAEs) of the estimated daily Ta using the EPC method ranged from 0.75-1.01 °C, which were 0.57-0.96 °C lower than that of the method in the literature. The biases of the estimated Ta obtained using the two methods were close to zero. However, the biases can be as high as 7.10 °C when Ta is extremely low and as low as -3.09 °C when Ta is extremely high. Compared with the method in the literature, the EPC method can reduce the MAE by 1.41 °C, root mean square error by 1.49 °C, and bias by 1.61 °C of the estimated extreme Ta. Additionally, the EPC method produced satisfactory accuracy (MAEs <0.9 °C) of the estimated heat and cold wave magnitudes. Finally, a 1 km resolution daily Ta map in east China from 2003 to 2012 was developed, which will be useful data in multiple research fields.


Assuntos
Temperatura Alta , Meteorologia , China , Temperatura Baixa , Meteorologia/métodos , Temperatura
19.
J Contam Hydrol ; 248: 104028, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35640420

RESUMO

Microplastics are emerging pollutants with sizes less than 5 mm, and they are ubiquitous. The occurrence of algal blooms has become a major problem affecting water quality in Chaohu Lake. To understand the relationship between the microplastic distribution and algal bloom density from a macroscopic point of view in Chaohu Lake, we collected microplastic samples from water and sediments during the wet and dry seasons and collected satellite remote sensing images of the algae density in recent years. The research results showed that the spatial and temporal distributions of microplastics were uneven and varied greatly. The average abundances of microplastics in the water samples were 2133 ± 1534 n•m-3 in the dry season and 1679 ± 1577 n•m-3 in the wet season, and the average abundance of microplastics in sediments was 308 ± 231 n•kg-1. The abundance of microplastics in the estuaries was higher than those in other locations, and it was higher in the western part of the lake than in the eastern part. The microplastics in water and sediments presented different sizes, colors, shapes and compositions. The abundance, distribution and migration of microplastics were mainly affected by population density, rainfall, runoff, hydrodynamic force and wind direction. At a more macroscopic level, the distribution of microplastics was similar to that of algal blooms, TN and TP to some extent, especially in the early stage of algal bloom outbreaks, and the algal density was significantly positively correlated with the flux of microplastics into the lake. Microplastics, as carriers of algae, could promote the growth of algae blooms in the early stage, while in the later stage, microplastics and algal blooms could aggregate and coprecipitate through adsorption or adhesion and then inhibit the growth of algae.


Assuntos
Lagos , Poluentes Químicos da Água , China , Monitoramento Ambiental , Eutrofização , Microplásticos , Plásticos , Poluentes Químicos da Água/análise
20.
Sci Rep ; 12(1): 5722, 2022 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-35388124

RESUMO

This study aimed to explore the ability of radiomics derived from both MRI and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) images to differentiate glioblastoma (GBM) from solitary brain metastases (SBM) and to investigate the combined application of multiple models. The imaging data of 100 patients with brain tumours (50 GBMs and 50 SBMs) were retrospectively analysed. Three model sets were built on MRI, 18F-FDG-PET, and MRI combined with 18F-FDG-PET using five feature selection methods and five classification algorithms. The model set with the highest average AUC value was selected, in which some models were selected and divided into Groups A, B, and C. Individual and joint voting predictions were performed in each group for the entire data. The model set based on MRI combined with 18F-FDG-PET had the highest average AUC compared with isolated MRI or 18F-FDG-PET. Joint voting prediction showed better performance than the individual prediction when all models reached an agreement. In conclusion, radiomics derived from MRI and 18F-FDG-PET could help differentiate GBM from SBM preoperatively. The combined application of multiple models can provide greater benefits.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Neoplasias Encefálicas/diagnóstico por imagem , Fluordesoxiglucose F18 , Glioblastoma/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Estudos Retrospectivos
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