Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.233
Filtrar
1.
Front Psychol ; 13: 978994, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092056

RESUMO

Objective: The main purpose of this study was to explore the association between early fundamental motor skills (FMS) and executive function (EF) in preschool children. Methods: A total of 394 young children (4.07 ± 0.76 years) were evaluated. The FMS and EF were evaluated using the Test of Gross Motor Development-2 (TGMD-2) and the NIH Toolbox Cognition Battery (NTCB), respectively. Results: Total FMS score was moderately and positively correlated with total EF score (r = 0.33, p < 0.001) and was a significant predictor of total EF score (ß = 0.37, p < 0.001). Specifically, locomotor skills were significant predictors of inhibition control (ß = 0.21, p < 0.001), working memory (ß = 0.18, p < 0.01), and cognitive flexibility (ß = 0.24, p < 0.001), while object control skills were only significant predictors of inhibition control (ß = 0.17, p < 0.01). Conclusion: FMS were significantly and positively correlated with EF and were significant predictors of EF. Early childhood policymakers, preschool teachers, and researchers should take these connections seriously and implement appropriate complex motor intervention programs in future teaching to stimulate the development of both motor and higher-order cognitive skills in preschool children.

2.
Front Cardiovasc Med ; 9: 946399, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119747

RESUMO

Background: The Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction (EMPEROR-Preserved) is the first randomized controlled trial to provide promising evidence on the efficacy of adding empagliflozin to the standard therapy in patients with Heart Failure with Preserved Ejection Fraction (HFpEF), but the cost-effectiveness of add-on empagliflozin treatment remains unclear. Method: A Markov model using data from the EMPEROR-Preserved trial and national database was constructed to assess lifetime costs and utility from a China healthcare system perspective. The time horizon was 10 years and a 5% discount rate was applied. Incremental cost-effectiveness ratio (ICER) against willingness to pay (WTP) threshold was performed to evaluate the cost-effectiveness. A series of sensitivity analyses was applied to ensure the robustness of the results. Results: Compared to standard therapy, the increased cost of adding empagliflozin from $4,645.23 to $5,916.50 was associated with a quality-adjusted life years (QALYs) gain from 4.70 to 4.81, projecting an ICER of $11,292.06, which was lower than a WTP threshold of $12,652.5. Univariate sensitivity analysis revealed that the parameters with the largest impact on ICER were cardiovascular mortality in both groups, followed by the cost of empagliflozin and the cost of hospitalization for heart failure. Probabilistic sensitivity analysis indicated that when the WTP threshold was $12,652.5 and $37,957.5, the probability of being cost-effective for adding empagliflozin was 52.7% and 67.6%, respectively. Scenario analysis demonstrated that the cost of empagliflozin, the cost of hospitalization for heart failure, NYHA functional classes, and time horizon had a greater impact on the ICER. Conclusion: At a WTP threshold of $12,652.5, the add-on empagliflozin treatment for HFpEF was cost-effective in healthcare systems in China, which promoted the rational use of empagliflozin for HFpEF.

3.
J Virol Methods ; 310: 114612, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36084767

RESUMO

Goose astrovirus (GAstV) is a highly infectious pathogen that causes gout in goslings (<15 old) with typical symptoms of white urate disposition on the surface of the visceral organs and articular cavity, and a high mortality rate up to 50 %. To establish a real-time reverse transcription-polymerase chain reaction (rRT-PCR) assay for the rapid detection of the two GastV genotypes(GAstV-1 and GAstV-2), two pairs of primers and a pair of matching TaqMan probes were designed based on conserved regions of the ORF1b gene. The established duplex rRT-PCR assay showed no cross-reactivity with 10 other common waterfowl pathogens. The minimum detection limit was 10 copies/reaction for both GAstV-1 and GAstV-2. To validate the assay, 36 cloacal swabs from experimentally infected goslings and 33 field clinical samples were tested. The assay results of the experimentally infected goslings matched the infection scheme. The positive rates of GAstV-1 and GAstV-2 in the field clinical samples were 36.36 % and 54.55 %, respectively, and the co-infection rate of the two viruses was 21.21 % based on the duplex rRT-PCR assay. In conclusion, the established assay represents a specific, sensitive, and convenient tool for detecting GAstV-1, GAstV-2, and their co-infections, and for conducting epidemiological surveys.

4.
Ann Transl Med ; 10(16): 886, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36111046

RESUMO

Background: Hepatic fibrosis is a widespread disease worldwide. Millions of people lose their lives due to hepatic fibrosis every year. The main causes of hepatic fibrosis include viral infection, alcoholism, and obesity. Many studies have been conducted on the single factors that cause hepatic fibrosis; however, no studies have examined whether hepatic fibrosis caused by multiple factors has concomitant expression molecules and signaling pathways. In this study, we sought to analyze the common differentially expressed messenger ribonucleic acids (mRNAs) of hepatic fibrosis caused by different factors, including hepatitis B virus (HBV) hepatic fibrosis, alcoholic hepatic fibrosis, and non-alcoholic hepatic fibrosis, and identify potential preventive and therapeutic targets. Methods: The GSE171294, GSE142530, and GSE126848 datasets from the Gene Expression Omnibus (GEO) public database were used in this study. A |log fold change| >0.5 and a P value <0.05 were defined as differentially expressed mRNAs via R software screening. To further screen the target mRNAs, the differential mRNAs were subjected to a functional enrichment analysis based on the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Finally, the relationships between differentially expressed mRNA-encoded proteins were analyzed by a protein-protein interaction (PPI) analysis. Results: A total of 54 differentially expressed mRNAs were identified. The KEGG analysis showed that the functions of different mRNAs mainly focused on Gonadotropin Releasing Hormone (GnRH) secretion, bile secretion and insulin secretion. The GO enrichment analysis showed that the differential mRNAs were mainly present in the cytoplasmic membrane region and exerted biological functions, such as activating channels and binding proteins by regulating biological processes (BPs), such as cells, cytoskeleton and heparin. The PPI network analysis revealed 16 nodes with 12 pairs of interactions. The 16 critical nodes included BCL6, CD4, CD24, IL32, CALD1, TRAF3, SOX9, KANSL3, MRGBP, PKD2, PKHD1, SYT1, ANXA4, KCNMA1, KCNN2, and CACNA1H. Conclusions: KCNN2, CD4, CD24, BCL6, KCNMA1, and other molecules obtained by the bioinformatics analysis of the RNA-sequencing data can be used as new research targets for hepatic fibrosis induced by different causes. Our findings could provide novel ideas for the treatment of hepatic fibrosis.

5.
Comput Intell Neurosci ; 2022: 3146637, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36052045

RESUMO

As an important part of the city, urban streets have always played an active role in carrying public needs and optimizing public living spaces. They are also important to open public spaces in the city. In addition, with technology integration and life, the interactive experience of artificial intelligence (AI) in Street View is gradually increasing. A streetscape planning and design method based on AI interactive experience is proposed. CSiXRevit 2022 software builds street simulation models for better street planning and design. Street digital imaging technology is used to analyze the original streetscape. Landscape features are integrated with the street model. Based on intelligent technology, urban landscape design is studied, and AI interactive experience is analyzed. Analytic hierarchy process (AHP) and AI technology evaluate the effect of landscape design. Firstly, AHP is used to construct the evaluation index system of the rural landscape design effect, and the index weight is determined. Back propagation neural network (BPNN) is used to construct an evaluation model of landscape design effect. Three indexes of target, project, and indicator layer are used to evaluate the effect of rural landscape design. The results show that (1) the variety and richness of streetscapes in the survey area should be increased. Interactive buildings should be placed on the street. (2) The comprehensive evaluation score of the street landscape is 0.60, and the design effect is excellent. The comprehensive evaluation values of the three project layers are 0.65, 0.48, and 0.67, respectively. The data show that the carrying capacity index of the study area is the best, and the vitality index is the weakest. Therefore, when designing the street landscape, the economic development has been strengthened by attracting investment, introducing large-scale exhibition shops, increasing street income, strengthening the construction of street public facilities, and paying attention to the public street experience. This work can provide references for related streetscape designs.


Assuntos
Inteligência Artificial , Meio Ambiente , Cidades , Inquéritos e Questionários
6.
J Helminthol ; 96: e65, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36065626

RESUMO

In this study, we report the first complete mitochondrial genome of the tapeworm Nippotaenia mogurndae in the order Nippotaeniidea Yamaguti, 1939. This mitogenome, which is 14,307 base pairs (bp) long with an A + T content of 72.2%, consists of 12 protein-coding genes, 22 transfer RNA (tRNA) genes, two rRNA genes, and two non-coding regions. Most tRNAs have a conventional cloverleaf structure, but trnS1 and trnR lack dihydrouridine arms of tRNA. The two largest non-coding regions, NCR1 (220 bp) and NCR2 (817 bp), are located between trnY and trnS2 and between nad5 and trnG, respectively. Phylogenetic analyses of mitogenomic data indicate that N. mogurndae is closely related to tapeworms in the order Cyclophyllidea.


Assuntos
Cestoides , Infecções por Cestoides , Genoma Mitocondrial , Animais , Cestoides/genética , Infecções por Cestoides/veterinária , Filogenia , RNA de Transferência/genética
7.
ACS Nano ; 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36149273

RESUMO

Molybdenum trioxide has served as a promising cathode material of rechargeable magnesium batteries (RMBs), because of its rich valence states and high theoretical capacity; yet, it still suffers from sluggish (de)intercalation kinetics and inreversible structure change for highly polarized Mg2+ in the interlayer and intralayer of structure. Herein, F- substitutional and H+ interstitial doping is proposed for α-MoO3 materials (denoted HMoOF) by the intralayer/interlayer engineering strategy to boost the performance of RMBs. F- substitutional doping generates molybdenum vacancies along the Mo-O-□ or Mo-F-□ configurations (where □ represents the cationic vacancy) for unlocking the inactive basal plane of the layered crystal structure, and it further accelerates Mg2+ diffusion along the b-axis. Interstitial-doped H+ can expand interlayer spacing for reducing Mg2+ energy barrier along the ac plane and serve as a "pillar" to stabilize the interlayer structure. Moreover, anion and cation dual doping trigger shallow impurity levels (acceptors levels and donor levels), which helps to easily acquire the electrons from the valence band and donate the electrons to the conduction band. Consequently, the HMoOF electrode exhibits a high reversible capacity (241 mA h g-1 at 0.1 A g-1), an excellent rate capability (137.4 mAh g-1 at 2 A g-1), and a long cycling stability (capacity retention of 98% after 800 cycles at 1 A g-1) in RMBs. This work affords meaningful insights in layered materials for developing high-kinetics and long-life RMBs.

8.
Quant Imaging Med Surg ; 12(9): 4502-4511, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36060604

RESUMO

Background: The myocardial status of patients who undergo percutaneous coronary intervention (PCI) must be evaluated accurately to enable treatment plans to be made for potential complications such as abrupt vessel closure, stent deformation, and myocardial chronic ischemia. This study examined the modality and clinical feasibility of iodine-based extracellular volume (ECV) assessment of the myocardium versus cardiovascular magnetic resonance (CMR) imaging in patients undergoing PCI. Methods: In all, 21 patients who underwent PCI were prospectively enrolled in the study. All patients underwent follow-up cardiac dual-layer spectral detector computed tomography (SDCT) and CMR imaging after PCI. Myocardial ECV was quantified by either computed tomography (ECVCT) or magnetic resonance (ECVMR) using iodine or T1-weighted mapping, respectively. The quality of SDCT and CMR images was independently assessed by two radiologists using a 4-point scale (1= poor and 4= excellent). Any patient with an image quality (IQ) score <2 was excluded. Consistency between radiologists was evaluated using intraclass correlation coefficients (ICC). Correlations between ECVCT and ECVMR values were analyzed using Pearson's test, and consistency was analyzed with Bland-Altman plots. Results: Nineteen of 21 patients completed both cardiac CT and CMR examinations, while three patients were excluded after IQ assessment (two with poor CMR IQ; one with a discontinuous coronary artery on CT images). The mean (±SD) IQ scores for CT and CMR images were 3.81±0.40 and 3.25±0.58, respectively, and interobserver agreement was good (ICC =0.93 and 0.92 for CT and CMR, respectively). The mean (±SD) ECVCT and ECVMR values were 35.93%±9.73% and 33.89%±7.51%, respectively, with good correlation (r=0.79, P<0.001). Bland-Altman analysis showed a difference of 2.04% (95% CI: -9.56%, 13.64%) between the ECVCT and ECVMR values. Conclusions: There is high correlation between iodine-based ECVCT and ECVMR values, which indicates that ECVCT is clinically feasible for evaluating the status of myocardial recovery in patients undergoing PCI.

9.
ACS Omega ; 7(34): 29813-29822, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36061678

RESUMO

The motion behavior of particles impacting on the liquid surface can affect the capture efficiency of particles. It was found that there are three kinds of motion behaviors after particle impact on the liquid surface: sinking, rebound, and oscillation. In this paper, the processes of micron fly-ash particles impacting on the liquid surface were experimentally studied under normal temperature and pressure. The impact of fly-ash particles on the liquid surface was simulated by a dynamic model. Based on force analysis, the dynamic model was developed and verified by experimental data to distinguish between three motion behaviors. Then, the sinking/rebound critical velocity and rebound/oscillation critical velocity were calculated by the dynamic model. The critical velocities of particles impacting on the liquid surface under different particle sizes, receding angles, and surface tension coefficients were analyzed. As the particle size increased, sinking/rebound critical velocity and rebound/oscillation critical velocity decreased. As the receding angle increased, sinking/rebound critical velocity remained unchanged, and the rebound/oscillation critical velocity decreased. As the liquid surface tension coefficient increased, sinking/rebound critical velocity and rebound/oscillation critical velocity increased. On this basis, the behaviors of particles impacting on the liquid at low velocity were analyzed.

10.
Front Neurol ; 13: 988854, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061997

RESUMO

To determine the possible role of matrix metallopeptidase (MMP)-8 and MMP-9 in the development of chronic subdural hematoma (CSDH), we investigated their expression in CSDH. In our previous study, we analyzed hematoma fluid and peripheral blood of 83 patients with CSDH, including 17 postoperative patients. Based on these results, we included 50 people in the normal group and analyzed 20 markers in the peripheral blood of each person. In order to identify representative markers, it was assessed by using overall differential gene expression. The concentration of MMP-8 was significantly higher in the normal group than that in the preoperative and postoperative groups. The concentration of MMP-9 was significantly lower in the normal group than in both preoperative and postoperative groups. Immunohistochemistry confirmed the expression of MMP-8 and MMP-9 in CSDH membranes. In conclusion, our results provide evidence of the expression of MMP-8 and MMP-9 in CSDH. In addition, the expression of MMP-8 and MMP-9 suggests angiogenesis in CSDH formation.

11.
Front Cell Dev Biol ; 10: 971992, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36081904

RESUMO

Background: Colon adenocarcinoma (COAD), a malignant gastrointestinal tumor, has the characteristics of high mortality and poor prognosis. Even in the presence of oxygen, the Warburg effect, a major metabolic hallmark of almost all cancer cells, is characterized by increased glycolysis and lactate fermentation, which supports biosynthesis and provides energy to sustain tumor cell growth and proliferation. However, a thorough investigation into glycolysis- and lactate-related genes and their association with COAD prognosis, immune cell infiltration, and drug candidates is currently lacking. Methods: COAD patient data and glycolysis- and lactate-related genes were retrieved from The Cancer Genome Atlas (TCGA) and Gene Set Enrichment Analysis (GSEA) databases, respectively. After univariate Cox regression analysis, a nonnegative matrix factorization (NMF) algorithm was used to identify glycolysis- and lactate-related molecular subtypes. Least absolute shrinkage and selection operator (LASSO) Cox regression identified twelve glycolysis- and lactate-related genes (ADTRP, ALDOB, APOBEC1, ASCL2, CEACAM7, CLCA1, CTXN1, FLNA, NAT2, OLFM4, PTPRU, and SNCG) related to prognosis. The median risk score was employed to separate patients into high- and low-risk groups. The prognostic efficacy of the glycolysis- and lactate-related gene signature was assessed using Kaplan-Meier (KM) survival and receiver operating characteristic (ROC) curve analyses. The nomogram, calibration curves, decision curve analysis (DCA), and clinical impact curve (CIC) were employed to improve the clinical applicability of the prognostic signature. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on differentially expressed genes (DEGs) from the high- and low-risk groups. Using CIBERSORT, ESTIMATE, and single-sample GSEA (ssGSEA) algorithms, the quantities and types of tumor-infiltrating immune cells were assessed. The tumor mutational burden (TMB) and cytolytic (CYT) activity scores were calculated between the high- and low-risk groups. Potential small-molecule agents were identified using the Connectivity Map (cMap) database and validated by molecular docking. To verify key core gene expression levels, quantitative real-time polymerase chain reaction (qRT-PCR) assays were conducted. Results: We identified four distinct molecular subtypes of COAD. Cluster 2 had the best prognosis, and clusters 1 and 3 had poor prognoses. High-risk COAD patients exhibited considerably poorer overall survival (OS) than low-risk COAD patients. The nomogram precisely predicted patient OS, with acceptable discrimination and excellent calibration. GO and KEGG pathway enrichment analyses of DEGs revealed enrichment mainly in the "glycosaminoglycan binding," "extracellular matrix," "pancreatic secretion," and "focal adhesion" pathways. Patients in the low-risk group exhibited a larger infiltration of memory CD4+ T cells and dendritic cells and a better prognosis than those in the high-risk group. The chemotherapeutic agent sensitivity of patients categorized by risk score varied significantly. We predicted six potential small-molecule agents binding to the core target of the glycolysis- and lactate-related gene signature. ALDOB and APOBEC1 mRNA expression was increased in COAD tissues, whereas CLCA1 and OLFM4 mRNA expression was increased in normal tissues. Conclusion: In summary, we identified molecular subtypes of COAD and developed a glycolysis- and lactate-related gene signature with significant prognostic value, which benefits COAD patients by informing more precise and effective treatment decisions.

12.
ACS Appl Mater Interfaces ; 14(36): 40491-40500, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36038135

RESUMO

Uncontrolled and excessive fibrosis after myocardial infarction (MI) in the peri-infarct zone leads to left ventricular remodeling and deterioration of cardiac function. Inhibiting fibroblast activation during the mature phase of cardiac repair improves cardiac remodeling and function after MI. Here, we engineered a biocompatible microneedle (MN) patch using gelatin methacryloyl and loaded it with galunisertib, a transforming growth factor-beta (TGF-ß)-specific inhibitor, to treat excessive cardiac fibrosis after MI. The MN patch could sustainably release galunisertib for more than 2 weeks and provide mechanical support for the fragile ventricular wall. After being applied to a rat model of MI, the galunisertib-loaded MN patch improved long-term cardiac function and reduced cardiac fibrosis by effectively inhibiting TGF-ß depending on fibroblast activation. This strategy shows the potential of the MN patch as an advanced platform to locally deliver direct antifibrotic drugs to prevent myocardial fibrosis for the treatment of MI and the promotion of cardiac repair.


Assuntos
Hidrogéis , Infarto do Miocárdio , Animais , Modelos Animais de Doenças , Fibrose , Gelatina , Metacrilatos , Infarto do Miocárdio/patologia , Miocárdio/patologia , Pirazóis , Quinolinas , Ratos , Fator de Crescimento Transformador beta
13.
ACS Omega ; 7(32): 27991-28002, 2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-35990436

RESUMO

In order to modify and optimize the performance of cement-based sealing materials and improve the gas drainage rate of boreholes. In this paper, nanosilica (NS), multiwalled carbon nanotubes (MWCNT), and graphene oxide (GO) were used to modify cement and optimize the pore structure. Uniaxial compression tests, X-ray diffraction (XRD), nuclear magnetic resonance (NMR), and combined fractal theory were used to analyze the mechanics and pore characteristics. The results show that the synergy of the three nanomaterials promotes the generation of hydration products such as calcium silicate hydrate (C-S-H) and ettringite (AFt), improves the total pore fractal dimension (D w) and seepage pore fractal dimension (D s), and optimizes the microscopic pore structure. However, when the content of NS increases from 2 to 4 wt %, the improvement in the mechanical properties is obviously weakened. The best ratio is where the SiO2 content is 2 wt %, the MWCNT content is 0.1 wt %, and the GO content is 0.03 wt %. Compared with pure cement, the fractal dimension increases significantly, the mechanical properties are increased by 24.7%, and the total porosity is reduced by 23.9%. This paper is of great significance for improving the efficiency of gas mining.

14.
Pain Med ; 2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-35997590

RESUMO

OBJECTIVE: To evaluate the effectiveness of Tuina in relieving the pain, negative emotions, and disability of patients with knee osteoarthritis (KOA). DESIGN: Single-centre, parallel, randomized controlled trial. SETTING: Shanghai Guanghua Integrated Chinese and Western Medicine Hospital, Shanghai, China. SUBJECTS: Adult patients with KOA who were able to speak Chinese and self-report symptoms were eligible. METHODS: A total of 104 patients were randomly allocated to receive the 6-week treatment of Tuina (Tuina group) or celecoxib (celecoxib group). Data on pain, negative emotions, and disability were collected at baseline, at week 2, 4 and 6, and follow-up (one month after the last treatment). The primary outcomes were the pressure pain thresholds. The secondary outcomes were: (1) numerical rating scale at rest and with movement; (2) Hamilton Anxiety Scale; (3) Hamilton Depression Scale; (4) Western Ontario and McMaster Universities Osteoarthritis Index; and (5) clinical effective rate. The adverse events of the trial were evaluated. RESULTS: In total, 99 patients completed the follow-up. Generalized linear mixed models were constructed to analyse the between-group differences. Statistically significant differences were found in the interaction effects (p < 0.05). In evaluating the group effect, statistical differences were found at week 6 and follow-up (p < 0.05). Further, all variables showed a time effect (p < 0.05). A statistical difference in the clinical effective rate was found between the Tuina and celecoxib groups (p < 0.05). CONCLUSIONS: Tuina produced superior effects for pain, negative emotions, and disability over time, as compared to celecoxib in patients with KOA.

16.
Front Endocrinol (Lausanne) ; 13: 950985, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35966089

RESUMO

The pregnane X receptor (PXR) is a master xenobiotic-sensing receptor in response to toxic byproducts, as well as a key regulator in intermediary lipid metabolism. Therefore, the present study was conducted to investigate the potential role of PXR in mediating the lipid dysregulation and xenobiotic responses under Cu-induced stress in largemouth bass (Micropterus salmoides). Four groups of largemouth bass (52.66 ± 0.03 g) were treated with control, Cu waterborne (9.44 µmol/L), Cu+RIF (Rifampicin, 100 mg/kg, PXR activator), and Cu+KET (Ketoconazole, 20 mg/kg, PXR inhibitor) for 48 h. Results showed that Cu exposure significantly elevated the plasma stress indicators and triggered antioxidant systems to counteract Cu-induced oxidative stress. Acute Cu exposure caused liver steatosis, as indicated by the significantly higher levels of plasma triglycerides (TG), lipid droplets, and mRNA levels of lipogenesis genes in the liver. Liver injuries were detected, as shown by hepatocyte vacuolization and severe apoptotic signals after Cu exposure. Importantly, Cu exposure significantly stimulated mRNA levels of PXR, suggesting the response of this regulator in the xenobiotic response. The pharmacological intervention of PXR by the agonist and antagonist significantly altered hepatic mRNA levels of PXR, implying that RIF and KET were effective agents of PXR in largemouth bass. Administration of RIF significantly exacerbated liver steatosis, and such alterations were dependent on the regulations on pparγ and cd36 rather than srebp1 signaling, which suggested that PXR-PPARγ might be another pathway for Cu-induced lipid deposition in fish. Whereas, KET administration showed reverse effects on lipid metabolism as indicated by the lower hepatic TG levels, suppressed mRNA levels of pparγ and cd36. Activation of PXR stimulated autophagy and inhibited apoptosis, leading to lower hepatic vacuolization; while inhibition of PXR showed higher apoptotic signals, inhibition of autophagic genes and stimulation of apoptotic genes. Taken together, PXR played a cytoprotective role in Cu-induced hepatotoxicity through regulations on autophagy and apoptosis. Overall, our data has demonstrated for the first time on the dual roles of PXR as a co-regulator in mediating xenobiotic responses and lipid metabolism in fish, which implying the potential of PXR as a therapy target for xenobiotics-induced lipid dysregulation and hepatotoxicity.


Assuntos
Bass , Doença Hepática Induzida por Substâncias e Drogas , Fígado Gorduroso , Receptores de Esteroides , Animais , Antígenos CD36/metabolismo , Fígado Gorduroso/metabolismo , Metabolismo dos Lipídeos/fisiologia , PPAR gama/metabolismo , Receptor de Pregnano X/metabolismo , RNA Mensageiro/metabolismo , Receptores de Esteroides/genética , Triglicerídeos , Xenobióticos/farmacologia
18.
Front Neuroanat ; 16: 968320, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36032994

RESUMO

Recently, researchers have paid progressively more attention to the study of neural development in infant rats. However, due to the lack of complete intracerebral localization information, such as clear nuclear cluster boundaries, identified main brain structures, and reliable stereotaxic coordinates, it is difficult and restricted to apply technical neuroscience to infant rat's brain. The present study was undertaken to refine the atlas of infant rats. As such, we established a stereotaxic atlas of the infant rat's brain at postnatal days 7-13. Furthermore, dye calibration surgery was performed in P7-P13 infant rats by injecting Methylene blue, and sections were incubated in Nissl solutions. From the panoramic images of the brain sections, atlases were made. Our article has provided the appearance and measurements of P7-P13 Sprague-Dawley rat pups. Whereas the atlas contains a series of about 530 coronal brain section images from olfactory bulbs to the brainstem, a list of abbreviations of the main brain structures, and reliable stereotaxic coordinates, which were demonstrated by vertical and oblique injections with fluorescent dye DiI. The present findings demonstrated that our study of P7-P13 atlases has reasonable nucleus boundaries and accurate and good repeatability of stereotaxic coordinates, which can make up for the shortage of postnatal rat brain atlas currently in the field.

19.
Cell Mol Immunol ; 19(9): 1030-1041, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35962189

RESUMO

Aberrant expression of Myc is one of the most common oncogenic events in human cancers. Scores of Myc inhibitors are currently under development for treating Myc-driven cancers. In addition to directly targeting tumor cells, Myc inhibition has been shown to modulate the tumor microenvironment to promote tumor regression. However, the effect of Myc inhibition on immune cells in the tumor microenvironment remains poorly understood. Here, we show that the adaptive immune system plays a vital role in the antitumor effect of pharmacologic inhibition of Myc. Combining genetic and pharmacologic approaches, we found that Myc inhibition enhanced CD8 T cell function by suppressing the homeostasis of regulatory T (Treg) cells and the differentiation of resting Treg (rTreg) cells to activated Treg (aTreg) cells in tumors. Importantly, we demonstrated that different Myc expression levels confer differential sensitivity of T cell subsets to pharmacologic inhibition of Myc. Although ablation of the Myc gene has been shown to suppress CD8 T cell function, Treg cells, which express much less Myc protein than CD8 T cells, are more sensitive to Myc inhibitors. The differential sensitivity of CD8 T and Treg cells to Myc inhibitors resulted in enhanced CD8 T cell function upon Myc inhibition. Our findings revealed that Myc inhibitors can induce an antitumor immune response during tumor progression.


Assuntos
Neoplasias , Linfócitos T Reguladores , Linfócitos T CD8-Positivos , Humanos , Subpopulações de Linfócitos T , Microambiente Tumoral
20.
Artigo em Inglês | MEDLINE | ID: mdl-36008690

RESUMO

PURPOSE: The aim of this retrospective study is to evaluate the impact on efficacy and safety between epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) alone and in combination with Shenqi Fuzheng injection (SFI) in patients with advanced NSCLC harboring epidermal growth factor receptor (EGFR) activating mutations. METHODS: Retrospectively, information of 88 patients receiving EGFR-TKIs as first-line targeted treatment or in combination with SFI in the Affiliated Drum Tower Hospital of Nanjing University Medical College and the Affiliated Cancer Hospital of Anhui University of Science and Technology was collected. The primary endpoint was to assess progression-free survival (PFS) and safety of EGFR-TKIs alone or in combination with SFI. RESULTS: Between January 2016 and December 2019, a total of 88 patients were enrolled in this research, including 50 cases in the EGFR-TKIs single agent therapy group and 38 cases in the SFI combined with EGFR-TKIs targeted-therapy group. The median PFS (mPFS) of monotherapy group was 10.50 months (95%CI 9.81-11.19), and 14.30 months (95%CI 10.22-18.38) in the combination therapy group. Compared to the single EGFR-TKIs administration, combinational regimen with SFI exhibited a lower incidence of rash and diarrhea in patients and was even better tolerated. CONCLUSIONS: SFI combined with the first-generation EGFR-TKIs are more efficient, can prominently prolong the PFS and attenuate the adverse reactions in patients with advanced NSCLC with EGFR-sensitive mutations.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...