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1.
J Am Chem Soc ; 146(26): 17679-17690, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38889404

RESUMO

The complex interrelationships among thermoelectric parameters mean that a priori design of high-performing materials is difficult. However, band engineering can allow the power factor to be optimized through enhancement of the Seebeck coefficient. Herein, using layered Sb2Si2Te6 and Sc2Si2Te6 as model systems, we comprehensively investigate and compare their thermoelectric properties by employing density functional theory combined with semiclassical Boltzmann transport theory. Our simulations reveal that Sb2Si2Te6 exhibits superior electrical conductivity compared to Sc2Si2Te6 due to lower scattering rates and more pronounced band dispersion. Remarkably, despite Sb2Si2Te6 exhibiting a lower lattice thermal conductivity and superior electrical conductivity, Sc2Si2Te6 is predicted to achieve an extraordinary dimensionless figure of merit (ZT) of 3.51 at 1000 K, which significantly surpasses the predicted maximum ZT of 2.76 for Sb2Si2Te6 at 900 K. We find the origin of this behavior to be a combined increase in band (valley) degeneracy and anisotropy upon switching the conduction band orbital character from Sb p to Sc d, yielding a significantly improved Seebeck coefficient. This work suggests that enhancing band degeneracy and anisotropy (complexity) through compositional variation is an effective strategy for improving the thermoelectric performance of layered materials.

2.
Biochem Biophys Res Commun ; 701: 149525, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38320423

RESUMO

Angiogenesis, a finely regulated process, plays a crucial role in the progression of various diseases. Cerebral cavernous malformation 3 (CCM3), alternatively referred to as programmed cell death 10 (PDCD10), stands as a pivotal functional gene with a broad distribution across the human body. However, the precise role of CCM3 in angiogenesis regulation has remained elusive. YAP/TAZ, as core components of the evolutionarily conserved Hippo pathway, have garnered increasing attention as a novel mechanism in angiogenesis regulation. Nonetheless, whether CCM3 regulates angiogenesis through YAP/TAZ mediation has not been comprehensively explored. In this study, our primary focus centers on investigating the regulation of angiogenesis through CCM3 knockdown mediated by YAP/TAZ. Silencing CCM3 significantly enhances the proliferation, migration, and tubular formation of human umbilical vein endothelial cells (HUVECs), thereby promoting angiogenesis. Furthermore, we observe an upregulation in the expression levels of VEGF and VEGFR2 within HUVECs upon silencing CCM3. Mechanistically, the evidence we provide suggests for the first time that endothelial cell CCM3 knockdown induces the activation and nuclear translocation of YAP/TAZ. Finally, we further demonstrate that the YAP/TAZ inhibitor verteporfin can reverse the pro-angiogenic effects of siCCM3, thereby confirming the role of CCM3 in angiogenesis regulation dependent on YAP/TAZ. In summary, our findings pave the way for potential therapeutic targeting of the CCM3-YAP/TAZ signaling axis as a novel approach to promote angiogenesis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Angiogênese , Proteínas Reguladoras de Apoptose , Proteínas de Membrana , Proteínas Proto-Oncogênicas , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional , Proteínas de Sinalização YAP , Humanos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Angiogênese/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Fosfoproteínas/metabolismo , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Proto-Oncogênicas/metabolismo
3.
Small ; : e2311317, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38712469

RESUMO

The advent of 2D materials has ushered in the exploration of their synthesis, characterization and application. While plenty of 2D materials have been synthesized on various metallic substrates, interfacial interaction significantly affects their intrinsic electronic properties. Additionally, the complex transfer process presents further challenges. In this context, experimental efforts are devoted to the direct growth on technologically important semiconductor/insulator substrates. This review aims to uncover the effects of substrate on the growth of 2D materials. The focus is on non-metallic substrate used for epitaxial growth and how this highlights the necessity for phase engineering and advanced characterization at atomic scale. Special attention is paid to monoelemental 2D structures with topological properties. The conclusion is drawn through a discussion of the requirements for integrating 2D materials with current semiconductor-based technology and the unique properties of heterostructures based on 2D materials. Overall, this review describes how 2D materials can be fabricated directly on non-metallic substrates and the exploration of growth mechanism at atomic scale.

4.
Plant Cell ; 33(12): 3658-3674, 2021 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-34524462

RESUMO

Protons (H+) in acidic soils arrest plant growth. However, the mechanisms by which plants optimize their biological processes to diminish the unfavorable effects of H+ stress remain largely unclear. Here, we showed that in the roots of Arabidopsis thaliana, the C2H2-type transcription factor STOP1 in the nucleus was enriched by low pH in a nitrate-independent manner, with the spatial expression pattern of NITRATE TRANSPORTER 1.1 (NRT1.1) established by low pH required the action of STOP1. Additionally, the nrt1.1 and stop1 mutants, as well as the nrt1.1 stop1 double mutant, had a similar hypersensitive phenotype to low pH, indicating that STOP1 and NRT1.1 function in the same pathway for H+ tolerance. Molecular assays revealed that STOP1 directly bound to the promoter of NRT1.1 to activate its transcription in response to low pH, thus upregulating its nitrate uptake. This action improved the nitrogen use efficiency (NUE) of plants and created a favorable rhizospheric pH for root growth by enhancing H+ depletion in the rhizosphere. Consequently, the constitutive expression of NRT1.1 in stop1 mutants abolished the hypersensitive phenotype to low pH. These results demonstrate that STOP1-NRT1.1 is a key module for plants to optimize NUE and ensure better plant growth in acidic media.


Assuntos
Proteínas de Transporte de Ânions/genética , Proteínas de Arabidopsis/genética , Arabidopsis/fisiologia , Nitratos/metabolismo , Proteínas de Plantas/genética , Rizosfera , Solo/química , Fatores de Transcrição/genética , Adaptação Fisiológica/genética , Proteínas de Transporte de Ânions/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Transporte Biológico , Concentração de Íons de Hidrogênio , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo
5.
Ann Hematol ; 103(5): 1697-1704, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38536476

RESUMO

Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) stands as a pivotal treatment for hematologic malignancies, often considered the sole effective treatment option. A frequent complication following allo-HSCT is poor graft function (PGF), with one of its primary manifestations being persistent thrombocytopenia (PT), comprising prolonged isolated thrombocytopenia (PIT) and secondary failure of platelet recovery (SFPR). Conventional treatment methods have had poor efficacy and a high transplantation-associated mortality rate. In recent years, the efficacy of eltrombopag has been reported in the treatment of post-transplantation PT, and additional thrombopoietin receptor agonists (TPO-RA) have been developed. Herombopag is a next-generation TPO-RA which has strong proliferation-promoting effects on human TPO-R-expressing cells (32D-MPL) and hematopoietic progenitor cells in vitro. We reviewed eighteen patients with transplantation-associated thrombocytopenia who received herombopag when eltrombopag was ineffective or poorly tolerated and evaluated its efficacy including effects on survival. Herombopag was administered at a median time of 197 days post-transplantation. Six patients achieved complete response (CR), with a median time to CR of 56 days. Five patients achieved partial response (PR), and the median time to PR was 43 days. Seven patients were considered to have no response (NR). The overall response (OR) rate was 61.1%, and the cumulative incidence (CI) of OR was 90.2%. No patients developed herombopag-associated grade 3-4 toxicity. The median follow-up period was 6.5 months. Twelve patients survived and six patients died, with an overall survival rate of 66.7%. This is the first study to demonstrate the efficacy and safety of herombopag in transplantation-associated thrombocytopenia after failing eltrombopag, introducing a new approach in the treatment of PT following allo-HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Pirazóis , Trombocitopenia , Humanos , Trombocitopenia/tratamento farmacológico , Trombocitopenia/etiologia , Benzoatos/uso terapêutico , Benzoatos/farmacologia , Hidrazinas/uso terapêutico , Hidrazinas/farmacologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Resposta Patológica Completa , Estudos Retrospectivos
6.
Anticancer Drugs ; 35(2): 163-176, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37948318

RESUMO

Chemotherapy is the main treatment option for acute myeloid leukemia (AML), but acquired resistance of leukemic cells to chemotherapeutic agents often leads to difficulties in AML treatment and disease relapse. High calcitonin receptor-like (CALCRL) expression is closely associated with poorer prognosis in AML patients. Therefore, this study was performed by performing CALCRL overexpression constructs in AML cell lines HL-60 and Molm-13 with low CALCRL expression. The results showed that overexpression of CALCRL in HL-60 and Molm-13 could confer resistance properties to AML cells and reduce the DNA damage and cell cycle G0/G1 phase blocking effects caused by daunorubicin (DNR) and others. Overexpression of CALCRL also reduced DNR-induced apoptosis. Mechanistically, the Cancer Clinical Research Database analyzed a significant positive correlation between XRCC5 and CALCRL in AML patients. Therefore, the combination of RT-PCR and Western blot studies further confirmed that the expression levels of XRCC5 and PDK1 genes and proteins were significantly upregulated after overexpression of CALCRL. In contrast, the phosphorylation levels of AKT/PKCε protein, a downstream pathway of XRCC5/PDK1, were significantly upregulated. In the response study, transfection of overexpressed CALCRL cells with XRCC5 siRNA significantly upregulated the drug sensitivity of AML to DNR. The expression levels of PDK1 protein and AKT/PKCε phosphorylated protein in the downstream pathway were inhibited considerably, and the expression of apoptosis-related proteins Bax and cleaved caspase-3 were upregulated. Animal experiments showed that the inhibitory effect of DNR on the growth of HL-60 cells and the number of bone marrow invasions were significantly reversed after overexpression of CALCRL in nude mice. However, infection of XCRR5 shRNA lentivirus in HL-60 cells with CALCRL overexpression attenuated the effect of CALCRL overexpression and upregulated the expression of apoptosis-related proteins induced by DNR. This study provides a preliminary explanation for the relationship between high CALCRL expression and poor prognosis of chemotherapy in AML patients. It offers a more experimental basis for DNR combined with molecular targets for precise treatment in subsequent studies.


Assuntos
Daunorrubicina , Leucemia Mieloide Aguda , Animais , Camundongos , Humanos , Daunorrubicina/farmacologia , Regulação para Cima , Camundongos Nus , Proteínas Proto-Oncogênicas c-akt/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Células HL-60 , Apoptose , Autoantígeno Ku/genética , Autoantígeno Ku/metabolismo , Autoantígeno Ku/farmacologia , TYK2 Quinase/genética , TYK2 Quinase/metabolismo , TYK2 Quinase/farmacologia , Janus Quinase 1/genética , Janus Quinase 1/metabolismo , Janus Quinase 1/farmacologia , Proteína Semelhante a Receptor de Calcitonina/genética , Proteína Semelhante a Receptor de Calcitonina/metabolismo
7.
EMBO Rep ; 23(9): e54128, 2022 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-35876654

RESUMO

The long noncoding RNA LINC00839 has been shown to be involved in the progression of some cancer types, such as bladder cancer, prostate cancer, breast cancer, and neuroblastoma. However, if LINC00839 has roles in colorectal cancer (CRC), it has not been elucidated so far. Here, we focus on the biological role and involved mechanisms of LINC00839 in CRC. We show that LINC00839 is selectively upregulated in CRC and locates to the nucleus. High expression of LINC00839 is associated with poor outcomes in CRC patients. Functional experiments show that LINC00839 promotes CRC proliferation, invasion, and metastasis in vitro and in vivo. Mechanistically, LINC00839 recruits Ruvb1 to the Tip60 complex and increases its acetylase activity. LINC00839 guides the complex to the NRF1 promoter and promotes acetylation of lysines 5 and 8 of histones H4, thereby upregulating the expression of NRF1. Subsequently, NRF1 activates mitochondrial metabolism and biogenesis, thereby promoting CRC progression. In summary, our study reports on a mechanism by which LINC00839 positively regulates NRF1, thus promoting mitochondrial metabolism and biogenesis, as well as CRC progression.


Assuntos
Neoplasias Colorretais , RNA Longo não Codificante , ATPases Associadas a Diversas Atividades Celulares/genética , ATPases Associadas a Diversas Atividades Celulares/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/genética , Neoplasias Colorretais/metabolismo , DNA Helicases/genética , DNA Helicases/metabolismo , Regulação Neoplásica da Expressão Gênica , Histonas/metabolismo , Humanos , Lisina Acetiltransferase 5/metabolismo , Masculino , Fator 1 Nuclear Respiratório/metabolismo , Regiões Promotoras Genéticas , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
8.
Eur J Clin Pharmacol ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38904800

RESUMO

OBJECTIVE: This paper was aimed at unveiling the effect of low-molecular-weight heparin calcium (LMWH) combined with magnesium sulfate and labetalol on coagulation, vascular endothelial function, and pregnancy outcome in early-onset severe preeclampsia (EOSP). METHODS: Pregnant women with EOSP were divided into the control group and the study group, each with 62 cases. Patients in the control group were treated with labetalol and magnesium sulfate, and those in the study group were treated with LMWH in combination with the control grou Blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]), 24-h urine protein, coagulation indices [D-dimer (D-D), plasma fibrinogen (Fg), prothrombin time (PT), activated partial thromboplastin time (APTT), and prothrombin time (TT)], endothelial function [endothelin (ET-1) and nitric oxide (NO)], oxidative stress indices [oxidized low-density lipoproteins (ox-LDL), lipid peroxidation (LPO), superoxide dismutase (SOD), and malondialdehyde (MDA)], pregnancy outcome, and adverse effects occurred in the two groups were compared. RESULTS: After treatment, lower SBP, DBP, and 24-h urine protein levels; lower Fg and D-D levels; higher PT, APPT, and TT levels; higher NO levels; lower ET-1 levels; lower ox-LDL, MDA, and LPO levels; higher SOD levels; and lower incidence of adverse pregnancy and adverse reactions were noted in the study group in contrast to the control group. CONCLUSION: EOSP patients given with LMWH combined with magnesium sulfate and labetalol can effectively reduce the patient's blood pressure and urinary protein level; improve coagulation function, oxidative stress, and vascular endothelial function indices; reduce the adverse pregnancy outcomes; and improve the safety of treatment.

9.
Graefes Arch Clin Exp Ophthalmol ; 262(5): 1409-1419, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37815595

RESUMO

PURPOSE: To compare the efficacy of different anti-vascular endothelial growth factor (VEGF) agents for the treatment of retinopathy of prematurity (ROP) in preterm infants. METHODS: Seven databases were searched for eligible literature up to February 22, 2023. Studies were included if they were randomised controlled trials (RCTs) investigating the efficacy of anti-VEGF agents for ROP in infants. A network meta-analysis (NMA) was performed. We also conducted subgroup analyses to determine the efficacy ranking of regimens used in different regions. The odds ratio (OR), standardised mean difference (SMD), and surface under the cumulative ranking curve (SUCRA) were calculated for each outcome. RESULTS: Thirteen RCTs of 10 different regimens, involving 1196 infants (2388 eyes), were identified. Bevacizumab (0.625 mg; OR = 0.16, 95% confidence interval [CI] 0.06-0.40, SUCRA = 80.6%) and conbercept (0.15 mg; OR = 0.08, 95% CI 0.02-0.30, SUCRA = 96.0%) were the most effective regimens in reducing the risk of ROP recurrence requiring retreatment in Western countries and China, respectively. Compared with laser therapy, bevacizumab (0.625 mg; SMD = 1.54, 95% CI 0.06-3.02) achieved significantly longer intervals between treatment and recurrence. No significant difference in the risk of retinal detachment was detected between any anti-VEGF agent and laser (p > 0.05). CONCLUSIONS: Bevacizumab (0.625 mg) and conbercept (0.15 mg) appeared to be the most effective therapies for ROP in Western countries and China, respectively. More high-quality RCTs are warranted to evaluate the efficacy and long-term safety of anti-VEGF drugs for the management of ROP.

10.
Artigo em Inglês | MEDLINE | ID: mdl-38916485

RESUMO

BACKGROUND: The therapeutic impact of the Wenyang Huoxue (WYXH) formula on coronary atherosclerotic heart disease (CHD) is well established, yet the precise mechanisms are currently not fully understood. This study provides preliminary insights into the potential mechanisms underlying the therapeutic effects of the formula on CHD by utilizing network pharmacology and molecular docking technology. MATERIALS AND METHODS: The primary active constituents and their corresponding action targets for the formula were retrieved from the TCMSP database. Utilizing Cytoscape 3.9.1 software, a network linking the components of the formula to their respective targets was constructed. Information was collected from Genecards, OMIM, TTD, and DrugBank databases to identify targets related to CHD. The common targets shared by the formula and CHD were then imported into the STRING database to create a protein-protein interaction (PPI) network. Following this, enrichment analyses were performed on the shared targets using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, molecular docking was conducted on the primary active compounds and the core targets. RESULTS: The network encompassing the components and targets of the formula comprises a total of 311 nodes and 895 edges. Compounds exhibiting higher degree centrality consist of quercetin, ß-sitosterol, and kaempferol. In the PPI network, proteins with elevated degree centrality are protein kinase B (AKT1), epidermal growth factor receptor (EGFR), and mitogen-activated protein kinase 3 (MAPK3). The results of GO and KEGG enrichment analyses reveal that the biological processes associated with the efficacy of the formula in treating CHD primarily involve positive regulation of gene expression, hypoxia response, and lipopolysaccharide response, among others. The signaling pathways primarily involved include phosphatidylinositol 3-kinase and protein kinase B (PI3K-AKT), MAPK3, tumor necrosis factor (TNF), and so on. Molecular docking results demonstrate a strong affinity between quercetin, ß-sitosterol, and kaempferol with AKT1, EGFR, and MAPK3. CONCLUSION: We showed for the first time that AKT1, EGFR, and MAPK3 are potential targets influenced by the WYHX formula in CHD treatment. The therapeutic effects could possibly involve signaling pathways such as the PI3K-AKT, MAPK, TNF, and AGE-RAGE pathways.

11.
J Math Biol ; 88(6): 63, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619652

RESUMO

Age structure is one of the crucial factors in characterizing the heterogeneous epidemic transmission. Vaccination is regarded as an effective control measure for prevention and control epidemics. Due to the shortage of vaccine capacity during the outbreak of epidemics, how to design vaccination policy has become an urgent issue in suppressing the disease transmission. In this paper, we make an effort to propose an age-structured SVEIHR model with the disease-caused death to take account of dynamics of age-related vaccination policy for better understanding disease spread and control. We present an explicit expression of the basic reproduction number R 0 , which determines whether or not the disease persists, and then establish the existence and stability of endemic equilibria under certain conditions. Numerical simulations are illustrated to show that the age-related vaccination policy has a tremendous influence on curbing the disease transmission. Especially, vaccination of people over 65 is better than for people aged 21-65 in terms of rapid eradication of the disease in Italy.


Assuntos
Epidemias , Vacinação , Humanos , Surtos de Doenças/prevenção & controle , Número Básico de Reprodução , Epidemias/prevenção & controle , Itália
12.
Nucleic Acids Res ; 50(W1): W568-W576, 2022 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35639771

RESUMO

Most complex disease-associated loci mapped by genome-wide association studies (GWAS) are located in non-coding regions. It remains elusive which genes the associated loci regulate and in which tissues/cell types the regulation occurs. Here, we present PCGA (https://pmglab.top/pcga), a comprehensive web server for jointly estimating both associated tissues/cell types and susceptibility genes for complex phenotypes by GWAS summary statistics. The web server is built on our published method, DESE, which represents an effective method to mutually estimate driver tissues and genes by integrating GWAS summary statistics and transcriptome data. By collecting and processing extensive bulk and single-cell RNA sequencing datasets, PCGA has included expression profiles of 54 human tissues, 2,214 human cell types and 4,384 mouse cell types, which provide the basis for estimating associated tissues/cell types and genes for complex phenotypes. We develop a framework to sequentially estimate associated tissues and cell types of a complex phenotype according to their hierarchical relationships we curated. Meanwhile, we construct a phenotype-cell-gene association landscape by estimating the associated tissues/cell types and genes of 1,871 public GWASs. The association landscape is generally consistent with biological knowledge and can be searched and browsed at the PCGA website.


Assuntos
Células , Computadores , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Internet , Fenótipo , Software , Animais , Humanos , Camundongos , Estudo de Associação Genômica Ampla/métodos , Transcriptoma , Células/metabolismo , Especificidade de Órgãos
13.
Mar Drugs ; 22(2)2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38393047

RESUMO

Patients with ulcerative colitis (UC) have higher rates of depression. However, the mechanism of depression development remains unclear. The improvements of EPA and DHA on dextran sulfate sodium (DSS)-induced UC have been verified. Therefore, the present study mainly focused on the effects of EPA and DHA on UC-induced depression in C57BL/6 mice and the possible mechanisms involved. A forced swimming test and tail suspension experiment showed that EPA and DHA significantly improved DSS-induced depressive-like behavior. Further analysis demonstrated that EPA and DHA could significantly suppress the inflammation response of the gut and brain by regulating the NLRP3/ASC signal pathway. Moreover, intestine and brain barriers were maintained by enhancing ZO-1 and occludin expression. In addition, EPA and DHA also increased the serotonin (5-HT) concentration and synaptic proteins. Interestingly, EPA and DHA treatments increased the proportion of dominant bacteria, alpha diversity, and beta diversity. In conclusion, oral administration of EPA and DHA alleviated UC-induced depressive-like behavior in mice by modulating the inflammation, maintaining the mucosal and brain barriers, suppressing neuronal damage and reverting microbiota changes.


Assuntos
Colite Ulcerativa , Humanos , Camundongos , Animais , Sulfato de Dextrana/toxicidade , Camundongos Endogâmicos C57BL , Colite Ulcerativa/metabolismo , Transdução de Sinais , Inflamação/metabolismo , Modelos Animais de Doenças , Colo/metabolismo
14.
Biochem Genet ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38856955

RESUMO

Patients with chronic pelvic inflammation (CPI) experience irregular menstrual, ectopic pregnancy, and infertility. Yiyi Baijiang Decoction attenuates CPI in patients with uncovered mechanisms. CPI therapeutic targets intersected with those of Yiyi Baijiang Decoction, followed by importing into STRING to obtain protein-target interaction. "Drug-component-disease-target" interaction was constructed by Cytoscape. mRNA and protein levels were detected by real-time quantitative PCR (RT-qPCR) and western blot. Yiyi Baijiang Decoction contained 199 active ingredients. There were 1071 drug targets for Yiyi Baijiang Decoction and 1622 therapeutic targets for CPI. The GO functional enrichment analysis revealed 3445 biological processes, and the KEGG pathway enrichment analysis screened 67 signal pathways. Decreased ALB, increased protein kinase B (AKT1), interleukin (IL)-6, vascular endothelial growth factor A (VEGFA), and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K/AKT)-extracellular-regulated protein kinases (ERK)1/2 activation in CPI mice were abolished by Yiyi Baijiang Decoction. Yiyi Baijiang Decoction attenuates CPI by inactivating PI3K/AKT and ERK1/2 and regulating ALB, VEGFA, AKT1, and IL-6.

15.
Chem Biodivers ; 21(4): e202302053, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38270380

RESUMO

Five compounds (1-5), one long-chain fatty acid (1), two thiophenes (2 and 3), one alkaloid (4), and one phenyl ester (5), were isolated from the aerial part of Echinops davuricus. The structures of the products were established by performing detailed nuclear magnetic resonance (NMR) analysis, and the structure of compound 1 was determined via high-resolution electrospray ionization mass spectrometry (HRESIMS) and NMR. Compounds 1, 4, and 5 were isolated from Echinops davuricus for the first time. Based on network pharmacology methods, AKR1B10 was selected as a key anticancer target. Compounds 1 and 5 exhibited significant AKR1B10 inhibitory activities, with IC50 values of 156.0±1.00 and 146.2±1.50 nM, respectively, with epalrestat used as the positive control (81.09±0.61 nM). Additionally, the interactions between the active compounds and AKR1B10 were evaluated via molecular docking. Ultimately, the GO and KEGG enrichment analysis indicated that the key signaling pathways associated with the active compounds may be related to the PI3K-Akt, MAPK, apoptotic, cellular senescence, and TNF signaling pathways and the human diseases corresponding to the targets are cancer. Our study reveals for the first time the anticancer properties of Echinops davuricus and provides a comprehensive understanding of its application in traditional medicine.


Assuntos
Medicamentos de Ervas Chinesas , Fosfatidilinositol 3-Quinases , Humanos , Simulação de Acoplamento Molecular , Tenrecidae , Ésteres , Ácidos Graxos , Aldo-Ceto Redutases
16.
Nano Lett ; 23(1): 148-154, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36566458

RESUMO

The power of surface chemistry to create atomically precise nanoarchitectures offers intriguing opportunities to advance the field of quantum technology. Strategies for building artificial electronic lattices by individually positioning atoms or molecules result in precisely tailored structures but lack structural robustness. Here, taking the advantage of strong bonding of Br atoms on noble metal surfaces, we report the production of stable quantum corrals by dehalogenation of hexabromobenzene molecules on a preheated Au(111) surface. The byproducts, Br adatoms, are confined within a new surface reconstruction pattern and aggregate into nanopores with an average size of 3.7 ± 0.1 nm, which create atomic orbital-like quantum resonance states inside each corral due to the interference of scattered electron waves. Remarkably, the atomic orbitals can be hybridized into molecular-like orbitals with distinct bonding and antibonding states. Our study opens up an avenue to fabricate quantum structures with high yield and superior robustness.

17.
Drug Dev Res ; 85(1): e22137, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38349260

RESUMO

Acute myeloid leukemia (AML) patients with FLT3 internal tandem duplication (FLT3-ITD) and DNA methyltransferase 3A (DNMT3A) R882 double mutations had a worse prognosis compared with AML with FLT3-ITD or DNMT3A R882 single mutation. This study was designed to explore the specific role of Calcitonin Receptor Like (CALCRL) in AML with FLT3-ITD and DNMT3A R882 double mutations. MOLM13 cells were transduced with CRISPR knockout sgRNA constructs to establish the FTL3-ITD and DNMT3A-R882 double-mutated AML cell model. Quantitative real-time PCR and Western blot assay were carried out to examine corresponding gene and protein expression. Methylation of CALCRL promoter was measured by methylation-specific PCR (MSP). Cell viability, colony formation, flow cytometry, and sphere formation assays were conducted to determine cell proliferation, apoptosis, and stemness. MOLM13 cells were exposed to stepwise increasing concentrations of cytarabine (Ara-C) to generate MOLM13/Ara-C cells. An in vivo AML  animal model was established, and the tumor volume and weight were recorded. TUNEL assay was adopted to examine cell apoptosis in tumor tissues. DNMT3A-R882 mutation upregulated the expression of CALCRL while downregulated the DNA methylation level of CALCRL in MOLM13 cells. CALCRL knockdown greatly inhibited cell proliferation, promoted apoptosis and repressed cell stemness, accompanied with the downregulated Oct4, SOX2, and Nanog in DNMT3A-R882-mutated MOLM13 cells and MOLM13/Ara-C cells. Furthermore, CALCRL knockdown restricted tumor growth and the chemoresistance of AML in vivo, as well as inducing cell apoptosis in tumor tissues. Together, these data reveal that CALCRL is a vital regulator of leukemia cell survival and resistance to chemotherapy, suggesting CALCRL as a promising therapeutic target for the treatment of FTL3-ITD and DNMT3A-R882 double-mutated AML.


Assuntos
Leucemia Mieloide Aguda , Receptores da Calcitonina , Animais , Humanos , Resistencia a Medicamentos Antineoplásicos/genética , RNA Guia de Sistemas CRISPR-Cas , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Mutação , Citarabina , Tirosina Quinase 3 Semelhante a fms/genética , Proteína Semelhante a Receptor de Calcitonina
18.
J Psychosoc Oncol ; 42(2): 190-207, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37435866

RESUMO

OBJECTIVE: To explore the combined effects of mindfulness and psychological capital on mental health of breast cancer patients and to examine the mediating effect of positive emotions in their relationship. METHODS: A convenient sampling method was used in this study, and 522 breast cancer patients aged 18 to 59 who received chemotherapy in a tertiary cancer hospital were enrolled. Polynomial regression with response surface analysis was mainly employed to explore the relationship between mindfulness, psychological capital, and mental health. A block-variable approach was used to verify the mediating effect of positive emotions. RESULTS: In cases of congruence, mental health was better when mindfulness and psychological capital were both high instead of being both low (the slope of the congruence was 0.540, p < 0.001); In cases of incongruence, poorer mental health was found in breast cancer patients with low psychological capital and high mindfulness compared with those who had high psychological capital and low mindfulness (the slope of the incongruence was -0.338, p < 0.001), and the combined effects were a positive curve (positive U-shaped) related to mental health (ß = 0.102, p = 0.040). In addition, positive emotions played a mediating role in the relationship between the block variable (mindfulness and psychological capital) and mental health, and the indirect effect was 0.131. CONCLUSIONS: This study expanded the research on the effects of mindfulness and psychological capital in improving mental health as well as the conflict between the two variables related to mental health by employing a new analytical technique among breast cancer patients.


Assuntos
Neoplasias da Mama , Atenção Plena , Humanos , Feminino , Saúde Mental , Neoplasias da Mama/psicologia , Atenção Plena/métodos , Pacientes
19.
Angew Chem Int Ed Engl ; : e202406585, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38863281

RESUMO

Polymer electrolytes play a crucial role in advancing rechargeable magnesium batteries (RMBs) owing to their exceptional characteristics, including high flexibility, superior interface compatibility, broad electrochemical stability window, and enhanced safety features. Despite these advantages, research in this domain remains nascent, plagued by single preparation approaches and challenges associated with the compatibility between polymer electrolytes and Mg metal anode. In this study, we present a novel synthesis strategy to fabricate a glycerol α,α'-diallyl ether-3,6-dioxa-1,8-octanedithiol-based polymer electrolyte supported by glass fiber substrate (GDT@GF) through anion modification and thiol-ene click chemistry polymerization. The developed route exhibits novelty and high efficiency, leading to the production of GDT@GF membranes featuring exceptional mechanical properties, heightened ionic conductivity, elevated Mg2+ transference number, and commendable compatibility with Mg anode. The assembled modified Mo6S8||GDT@GF||Mg cells exhibit outstanding performance across a wide temperature range and address critical safety concerns, showcasing the potential for applications under extreme conditions. Our innovative preparation strategy offers a promising avenue for the advancement of polymer electrolytes in high-performance rechargeable magnesium batteries, while also opens up possibilities for future large-scale applications and the development of flexible electronic devices.

20.
Plant J ; 112(2): 549-564, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36062335

RESUMO

Iron deficiency is a major constraint for plant growth in calcareous soils. The interplay between NO3 - and Fe nutrition affects plant performance under Fe-deficient conditions. However, how NO3 - negatively regulates Fe nutrition at the molecular level in plants remains elusive. Here, we showed that the key nitrate transporter NRT1.1 in Arabidopsis plants, especially in the shoots, was markedly downregulated at post-translational levels by Fe deficiency. However, loss of NRT1.1 function alleviated Fe deficiency chlorosis, suggesting that downregulation of NRT1.1 by Fe deficiency favors plant tolerance to Fe deficiency. Further analysis showed that although disruption of NRT1.1 did not alter Fe levels in both the shoots and roots, it improved the reutilization of apoplastic Fe in shoots but not in roots. In addition, disruption of NRT1.1 prevented Fe deficiency-induced apoplastic alkalization in shoots by inhibiting apoplastic H+ depletion via NO3 - uptake. In vitro analysis showed that reduced pH facilitates release of cell wall-bound Fe. Thus, foliar spray with an acidic buffer promoted the reutilization of Fe in the leaf apoplast to enhance plant tolerance to Fe deficiency, while the opposite was true for the foliar spray with a neutral buffer. Thus, downregulation of the shoot-part function of NRT1.1 prevents apoplastic alkalization to ensure the reutilization of apoplastic Fe under Fe-deficient conditions. Our findings may provide a basis for elucidating the link between N and Fe nutrition in plants and insight to scrutinize the relevance of shoot-expressed NRT1.1 to the plant response to stress.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Ferro/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Raízes de Plantas/metabolismo , Proteínas de Arabidopsis/metabolismo , Solo , Regulação da Expressão Gênica de Plantas , Nitratos/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Transporte de Ânions/genética
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