Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 854
Filtrar
Más filtros

Tipo del documento
Intervalo de año de publicación
1.
Chem Rev ; 123(19): 11664-11721, 2023 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-37707958

RESUMEN

Microporous zeolites that can act as heterogeneous catalysts have continued to attract a great deal of academic and industrial interest, but current progress in their synthesis and application is restricted to single-phase zeolites, severely underestimating the potential of intergrowth frameworks. Compared with single-phase zeolites, intergrowth zeolites possess unique properties, such as different diffusion pathways and molecular confinement, or special crystalline pore environments for binding metal active sites. This review first focuses on the structural features and synthetic details of all the intergrowth zeolites, especially providing some insightful discussion of several potential frameworks. Subsequently, characterization methods for intergrowth zeolites are introduced, and highlighting fundamental features of these crystals. Then, the applications of intergrowth zeolites in several of the most active areas of catalysis are presented, including selective catalytic reduction of NOx by ammonia (NH3-SCR), methanol to olefins (MTO), petrochemicals and refining, fine chemicals production, and biomass conversion on Beta, and the relationship between structure and catalytic activity was profiled from the perspective of intergrowth grain boundary structure. Finally, the synthesis, characterization, and catalysis of intergrowth zeolites are summarized in a comprehensive discussion, and a brief outlook on the current challenges and future directions of intergrowth zeolites is indicated.

2.
Proc Natl Acad Sci U S A ; 119(39): e2202563119, 2022 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-36122234

RESUMEN

Hundreds of members have been synthesized and versatile applications have been promised for endofullerenes (EFs) in the past 30 y. However, the formation mechanism of EFs is still a long-standing puzzle to chemists, especially the mechanism of embedding clusters into charged carbon cages. Here, based on synthesis and structures of two representative vanadium-scandium-carbido/carbide EFs, VSc2C@Ih (7)-C80 and VSc2C2@Ih (7)-C80, a reasonable mechanism-C1 implantation (a carbon atom is implanted into carbon cage)-is proposed to interpret the evolution from VSc2C carbido to VSc2C2 carbide cluster. Supported by theoretical calculations together with crystallographic characterization, the single electron on vanadium (V) in VSc2C@Ih (7)-C80 is proved to facilitate the C1 implantation. While the V=C double bond is identified for VSc2C@Ih (7)-C80, after C1 implantation the distance between V and C atoms in VSc2C2@Ih (7)-C80 falls into the range of single bond lengths as previously shown in typical V-based organometallic complexes. This work exemplifies in situ self-driven implantation of an outer carbon atom into a charged carbon cage, which is different from previous heterogeneous implantation of nonmetal atoms (Group-V or -VIII atoms) driven by high-energy ion bombardment or high-pressure offline, and the proposed C1 implantation mechanism represents a heretofore unknown metal-carbon cluster encapsulation mechanism and can be the fundamental basis for EF family genesis.

3.
BMC Genomics ; 25(1): 194, 2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38373886

RESUMEN

BACKGROUND: Bone morphogenetic proteins (BMPs) are part of the transforming growth factor beta (TGF-ß) superfamily and play crucial roles in bone development, as well as in the formation and maintenance of various organs. Triplophysa dalaica, a small loach fish that primarily inhabits relatively high elevations and cooler water bodies, was the focus of this study. Understanding the function of BMP genes during the morphogenesis of T. dalaica helps to clarify the mechanisms of its evolution and serves as a reference for the study of BMP genes in other bony fishes. The data for the T. dalaica transcriptome and genome used in this investigation were derived from the outcomes of our laboratory sequencing. RESULTS: This study identified a total of 26 BMP genes, all of which, except for BMP1, possess similar TGF-ß structural domains. We conducted an analysis of these 26 BMP genes, examining their physicochemical properties, subcellular localization, phylogenetic relationships, covariance within and among species, chromosomal localization, gene structure, conserved motifs, conserved structural domains, and expression patterns. Our findings indicated that three BMP genes were associated with unstable proteins, while 11 BMP genes were located within the extracellular matrix. Furthermore, some BMP genes were duplicated, with the majority being enriched in the GO:0008083 pathway, which is related to growth factor activity. It was hypothesized that genes within the BMP1/3/11/15 subgroup (Group I) play a significant role in the growth and development of T. dalaica. By analyzing the expression patterns of proteins in nine tissues (gonad, kidney, gill, spleen, brain, liver, fin, heart, and muscle), we found that BMP genes play diverse regulatory roles during different stages of growth and development and exhibit characteristics of division of labor. CONCLUSIONS: This study contributes to a deeper understanding of BMP gene family member expression patterns in high-altitude, high-salinity environments and provides valuable insights for future research on the BMP gene family in bony fishes.


Asunto(s)
Proteínas Morfogenéticas Óseas , Cipriniformes , Animales , Filogenia , Proteínas Morfogenéticas Óseas/genética , Proteínas Morfogenéticas Óseas/metabolismo , Cipriniformes/genética , Factor de Crecimiento Transformador beta/genética , Transcriptoma
4.
Apoptosis ; 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38635022

RESUMEN

Hypoxic pulmonary hypertension (HPH) is a pathophysiological syndrome in which pulmonary vascular pressure increases under hypoxic stimulation and there is an urgent need to develop emerging therapies for the treatment of HPH. LncRNA MIR210HG is a long non-coding RNA closely related to hypoxia and has been widely reported in a variety of tumor diseases. But its mechanism in hypoxic pulmonary hypertension is not clear. In this study, we identified for the first time the potential effect of MIR210HG on disease progression in HPH. Furthermore, we investigated the underlying mechanism through which elevated levels of MIR210HG promotes the transition from a contractile phenotype to a synthetic phenotype in PASMCs under hypoxia via activation of autophagy-dependent ferroptosis pathway. While overexpression of HIF-2α in PASMCs under hypoxia significantly reversed the phenotypic changes induced by MIR210HG knockdown. We further investigated the potential positive regulatory relationship between STAT3 and the transcription of MIR210HG in PASMCs under hypoxic conditions. In addition, we established both in vivo and in vitro models of HPH to validate the differential expression of specific markers associated with hypoxia. Our findings suggest a potential mechanism of LncRNA MIR210HG in the progression of HPH and offer potential targets for disease intervention and treatment.

5.
Anal Chem ; 96(1): 531-537, 2024 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-38115190

RESUMEN

Electrochemical biosensing devices face challenges of severe nonspecific adsorption in complex biological matrices for the detection of biomarkers, and thus, there is a significant need for sensitive and antifouling biosensors. Herein, a sensitive electrochemical biosensor with antifouling and antiprotease hydrolysis ability was constructed for the detection of human epidermal growth factor receptor 2 (HER2) by integrating multifunctional branched peptides with distearoylphosphatidylethanolamine-poly(ethylene glycol) (DSPE-PEG) self-assembled bilayer. The peptide was designed to possess antifouling, antiprotease hydrolysis, and HER2 recognizing capabilities. Molecular dynamics simulations demonstrated that the DSPE was able to effectively self-assemble into a bilayer, and the water contact angle and electrochemical experiments verified that the combination of peptide with the DSPE-PEG bilayer was conducive to enhancing the hydrophilicity and antifouling performance of the modified surface. The constructed HER2 biosensor exhibited excellent antifouling and antiprotease hydrolysis capabilities, and it possessed a linear range of 1.0 pg mL-1 to 1.0 µg mL-1, and a limit of detection of 0.24 pg mL-1. In addition, the biosensor was able to detect HER2 in real human serum samples without significant biofouling, and the assaying results were highly consistent with those measured by the enzyme-linked immunosorbent assay (ELISA), indicating the promising potential of the antifouling biosensor for clinical diagnosis.


Asunto(s)
Incrustaciones Biológicas , Técnicas Biosensibles , Humanos , Técnicas Electroquímicas/métodos , Péptidos/química , Técnicas Biosensibles/métodos , Polietilenglicoles , Incrustaciones Biológicas/prevención & control , Inhibidores de Proteasas
6.
Biochem Biophys Res Commun ; 710: 149871, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38579538

RESUMEN

Brassinosteroid activated kinase 1 (BAK1) is a cell-surface coreceptor which plays multiple roles in innate immunity of plants. HopF2 is an effector secreted by the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 into Arabidopsis and suppresses host immune system through interaction with BAK1 as well as its downstream kinase MKK5. The association mechanism of HopF2 to BAK1 remains unclear, which prohibits our understanding and subsequent interfering of their interaction for pathogen management. Herein, we found the kinase domain of BAK1 (BAK1-KD) is sufficient for HopF2 association. With a combination of hydrogen/deuterium exchange mass spectrometry and mutational assays, we found a region of BAK1-KD N-lobe and a region of HopF2 head subdomain are critical for intermolecular interaction, which is also supported by unbiased protein-protein docking with ClusPro and kinase activity assay. Collectively, this research presents the interaction mechanism between Arabidopsis BAK1 and P. syringae HopF2, which could pave the way for bactericide development that blocking the functioning of HopF2 toward BAK1.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Pseudomonas syringae/fisiología , Brasinoesteroides , Proteínas Bacterianas/química , Proteínas de Arabidopsis/fisiología , Enfermedades de las Plantas/microbiología , Proteínas Serina-Treonina Quinasas/química
7.
Planta ; 260(1): 22, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38847958

RESUMEN

MAIN CONCLUSION: The SiMBR genes in foxtail millet were identified and studied. Heterologous expression of SiMBR2 in Arabidopsis can improve plant tolerance to drought stress by decreasing the level of reactive oxygen species. Foxtail millet (Setaria italica L.), a C4 crop recognized for its exceptional resistance to drought stress, presents an opportunity to improve the genetic resilience of other crops by examining its unique stress response genes and understanding the underlying molecular mechanisms of drought tolerance. In our previous study, we identified several genes linked to drought stress by transcriptome analysis, including SiMBR2 (Seita.7G226600), a member of the MED25 BINDING RING-H2 PROTEIN (MBR) gene family, which is related to protein ubiquitination. Here, we have identified ten SiMBR genes in foxtail millet and conducted analyses of their structural characteristics, chromosomal locations, cis-acting regulatory elements within their promoters, and predicted transcription patterns specific to various tissues or developmental stages using bioinformatic approaches. Further investigation of the stress response of SiMBR2 revealed that its transcription is induced by treatments with salicylic acid and gibberellic acid, as well as by salt and osmotic stresses, while exposure to high or low temperatures led to a decrease in its transcription levels. Heterologous expression of SiMBR2 in Arabidopsis thaliana enhanced the plant's tolerance to water deficit by reducing the accumulation of reactive oxygen species under drought stress. In summary, this study provides support for exploring the molecular mechanisms associated with drought resistance of SiMBR genes in foxtail millet and contributing to genetic improvement and molecular breeding in other crops.


Asunto(s)
Arabidopsis , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Setaria (Planta) , Estrés Fisiológico , Setaria (Planta)/genética , Setaria (Planta)/fisiología , Setaria (Planta)/efectos de los fármacos , Arabidopsis/genética , Arabidopsis/fisiología , Estrés Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Sequías , Plantas Modificadas Genéticamente , Familia de Multigenes , Regiones Promotoras Genéticas/genética , Especies Reactivas de Oxígeno/metabolismo
8.
J Transl Med ; 22(1): 253, 2024 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-38459561

RESUMEN

Tobacco pollutants are prevalent in the environment, leading to inadvertent exposure of pregnant females. Studies of these pollutants' toxic effects on embryonic development have not fully elucidated the potential underlying mechanisms. Therefore, in this study, we aimed to investigate the developmental toxicity induced by cigarette smoke extract (CSE) at concentrations of 0.25, 1, and 2.5% using a zebrafish embryo toxicity test and integrated transcriptomic analysis of microRNA (miRNA) and messenger RNA (mRNA). The findings revealed that CSE caused developmental toxicity, including increased mortality and decreased incubation rate, in a dose-dependent manner. Moreover, CSE induced malformations and apoptosis, specifically in the head and heart of zebrafish larvae. We used mRNA and miRNA sequencing analyses to compare changes in the expression of genes and miRNAs in zebrafish larvae. The bioinformatics analysis indicates that the mechanism underlying CSE-induced developmental toxicity was associated with compromised genetic material damage repair, deregulated apoptosis, and disturbed lipid metabolism. The enrichment analysis and RT-qPCR show that the ctsba gene plays a crucial function in embryo developmental apoptosis, and the fads2 gene mainly regulates lipid metabolic toxicity. The results of this study improve the understanding of CSE-induced developmental toxicity in zebrafish embryos and contribute insights into the formulation of novel preventive strategies against tobacco pollutants during early embryonic development.


Asunto(s)
Contaminantes Ambientales , MicroARNs , Animales , Femenino , Pez Cebra/genética , Pez Cebra/metabolismo , Embrión no Mamífero/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Contaminantes Ambientales/metabolismo , Contaminantes Ambientales/farmacología
9.
Rev Cardiovasc Med ; 25(3): 96, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-39076962

RESUMEN

Background: Atrial fibrillation (AF), which occurs four to six times more frequently in hypertrophic cardiomyopathy (HCM) patients than in the general population, is the most common persistent arrhythmia and has a substantial therapeutic consequence. In HCM patients, there are currently no discovered signs that could be utilized to identify AF. Methods: From 2018 to 2022, 493 individuals with a continuous diagnosis of HCM were examined at Beijing Anzhen Hospital. AF was proven using routine electrocardiography (ECG), 24-hour Holter ECGs, or bedside ECGs. Echocardiography and blood tests were performed for all patients. Analysis and comparison of the traits were performed in HCM patients with AF (n = 77) and without AF (n = 416). Results: Age (p < 0.001), prevalence of ventricular tachycardia (VT, p < 0.001), prevalence of pulmonary artery hypertension (p = 0.027), and albumin-to-globulin ratio (AGR, p = 0.046) were all significantly higher in patients with AF, compared to patients without AF. In multivariate logistic analysis, age (odds ratio [OR], 1.063; 95% confidence interval [CI], 1.032-1.095; p < 0.001), history of VT (OR, 2.702; 95% CI, 1.007-7.255; p = 0.048), AGR (OR, 3.477; 95% CI, 1.417-8.536; p = 0.007), left atrial diameter (OR, 1.132; 95% CI, 1.073-1.194; p < 0.001), left ventricular end-diastolic diameter (OR, 0.861; 95% CI, 0.762-0.974; p = 0.017), left ventricular end-systolic diameter (OR, 1.239; 95% CI, 1.083-1.417; p = 0.002), and peak A wave velocity (OR, 0.983; 95% CI, 0.972-0.994; p = 0.002) were independently associated with AF in HCM patients. In the receiver operating characteristic curve analysis, the area under the curve for the established model was 0.819 (95% CI, 0.755-0.883, p = 0.033), with a sensitivity and specificity of 0.763 and 0.816, respectively, for AF occurrence in HCM patients. Conclusions: In individuals with HCM, a history of VT and a higher AGR are independently linked to AF. Further investigation is necessary to determine whether increased AGR represents a risk factor for embolic stroke or cardiovascular death.

10.
Opt Lett ; 49(2): 206-209, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38194529

RESUMEN

We demonstrate the suppression of inhomogeneous dephasing of cold 87Rb atoms optically trapped inside a hollow-core fiber. The differential light shift (DLS) for the clock transition caused by the trapping beam is reduced by one order of magnitude through the use of a weak compensation laser beam that is spatially mode-matched to the trapping beam. The coherence of the DLS-compensated system is characterized by microwave Ramsey interferometry, which shows Ramsey fringes with a contrast of over 0.6 at a separation time of 10 ms. The dephasing time, measured by Ramsey spectroscopy at different separation times, reaches tens of milliseconds after DLS cancellation, limited by the residual DLS caused by mode mismatching between the two laser beams. This work paves the way for compact and portable fiber-guided atom interferometers.

11.
FASEB J ; 37(6): e22955, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37159387

RESUMEN

The pathogenesis of allergic rhinitis (AR)-related olfactory dysfunction (OD) remains unknown. Inhibiting microglial response in olfactory bulb (OB) can ameliorate AR-related OD, but no precise targets have been available. In this study, we established a mouse model of ovalbumin (OVA)-induced AR and combined with the application of P2X7 receptor (P2X7R)-specific antagonists and cell culture in conditioned medium to investigate the role and mechanism of OB microglial P2X7R in AR-related OD. Serum IgE and IL-5 levels determined via ELISA and federated the number of nose-scratching to affirm the success of OVA-induced AR mouse model. Buried food pellet test was used to evaluate the olfactory function of mice. The changes of IBA1, GFAP, P2X7R, IL-1ß, IL-1Ra, and CASPASE 1 were detected by quantitative polymerase chain reaction and western blotting. The levels of adenosine triphosphate (ATP) were determined by the commercialized kit. The morphological changes of microglia were assessed using immunofluorescence staining and Sholl analysis. Findings showed that AR-related OD was associated with OB microglia-mediated imbalance between IL-1ß and IL-1Ra. Treatment with BBG improved the olfactory function in AR mice with restoring the balance between IL-1ß and IL-1Ra. In vitro, the conditioned medium obtained after HNEpC treatment with Der p1 could activate HMC3 to arise inflammatory reaction basing on "ATP-P2X7R-Caspase 1" axis, while inhibition of its P2X7R suppressed the reaction. In brief, microglial P2X7R in OB is a direct effector molecule in AR-related OD and inhibition of it may be a new strategy for the treatment of AR-related OD.


Asunto(s)
Trastornos del Olfato , Receptores Purinérgicos P2X7 , Rinitis Alérgica , Animales , Ratones , Adenosina Trifosfato , Caspasa 1 , Medios de Cultivo Condicionados , Modelos Animales de Enfermedad , Proteína Antagonista del Receptor de Interleucina 1 , Microglía , Bulbo Olfatorio , Ovalbúmina , Receptores Purinérgicos P2X7/genética , Rinitis Alérgica/complicaciones
12.
Environ Sci Technol ; 58(1): 895-905, 2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38134359

RESUMEN

N2O is a common byproduct in the selective catalytic oxidation of ammonia, and its generation often needs to be inhibited due to its strong greenhouse effect. In this paper, using Ag/ZSO-Y as a model catalyst, the N2O selectivity was reduced by 30% through modulation of the electron metal-support interaction. The results demonstrate that the work function of the support can be regulated by the content of the doping element. As the Zr content increases in SnO2, the work function of the support decreases. Moreover, there is a positive correlation between the charge transfer amount and the work function of the support. A series of in situ DRIFTS and density functional theory calculations revealed that the -NO and -N reactions are the primary pathways for N2O formation. By adjustment of the work function of the support through varying the Zr doping level, the electronic structure of Ag NPs was further tuned, resulting in an increased reaction energy barrier for -NO and -N reactions, effectively suppressing N2O formation.


Asunto(s)
Amoníaco , Electrones , Amoníaco/química , Amoníaco/metabolismo , Oxidación-Reducción , Metales , Catálisis
13.
Jpn J Clin Oncol ; 54(1): 89-96, 2024 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-37721193

RESUMEN

OBJECTIVE: Numerous scattered case studies continue to demonstrate a strong correlation between acquired KRAS mutations and epidermal growth factor receptor-tyrosine kinase inhibitor resistance in non-small cell lung cancer. However, the comprehensive understanding of the KRAS pathway following the failure of epidermal growth factor receptor-tyrosine kinase inhibitor therapy remains limited. METHODS: We conducted a retrospective evaluation of the next generation sequencing data from 323 patients with advanced non-small cell lung cancer and EGFR-activating mutations after experiencing progression with epidermal growth factor receptor-tyrosine kinase inhibitor therapy. Our analysis specifically focused on the acquired changes to the KRAS gene. RESULTS: Among the 323 patients with advanced non-small cell lung cancer and EGFR-activating mutations who experienced resistance to epidermal growth factor receptor-tyrosine kinase inhibitor therapy, 14 individuals (4.3%) developed resistance due to acquired KRAS alterations. Of these 14 patients, 10 cases (71.4%) were due to KRAS missense mutations, 1 case (7.2%) was due to KRAS gene fusion and 3 cases (21.4%) were due to KRAS amplification. Notably, we identified one newly demonstrated KRAS gene fusion (KRAS and LMNTD1), one KRAS G13D and one KRAS K117N. The emergence of acquired KRAS alterations was often accompanied by novel mutations and high tumor mutation burden, with TP53, CNKN2A, PIK3CA, MYC, STK11, CDK4, BRCA2 and ERBB2 being the most frequently observed concurrent mutations. The median progression-free survival and overall survival for the 14 patients were 5.2 and 7.3 months, respectively. Acquired KRAS missense variants were associated with significantly worse progression-free survival compared with other KRAS variant subtypes (P < 0.028). CONCLUSIONS: This study provides significant evidence of the role of acquired KRAS variants in the development of resistance to epidermal growth factor receptor-tyrosine kinase inhibitor therapy. Our results contribute to the growing body of knowledge on the mutational profiles associated with resistance to epidermal growth factor receptor-tyrosine kinase inhibitor treatment. Furthermore, our study highlights the KRAS gene change as a significant mechanism of resistance to epidermal growth factor receptor-tyrosine kinase inhibitor therapy.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Proteínas Proto-Oncogénicas p21(ras)/genética , Estudios Retrospectivos , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Quinazolinas , Receptores ErbB/genética , Mutación , Resistencia a Antineoplásicos/genética
14.
Acta Pharmacol Sin ; 45(6): 1264-1275, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38438582

RESUMEN

In addition to the classical resistance mechanisms, receptor tyrosine-protein kinase AXL is a main mechanism of resistance to third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) osimertinib in EGFR-mutated non-small cell lung cancer (NSCLC). Developing an effective AXL inhibitor is important to sensitize osimertinib in clinical application. In this study we assessed the efficacy of brigatinib, a second-generation of anaplastic lymphoma kinase (ALK)-TKI, as a novel AXL inhibitor, in overcoming acquired resistance to osimertinib induced by AXL activation. We established an AXL-overexpression NSCLC cell line and conducted high-throughput screening of a small molecule chemical library containing 510 anti-tumor drugs. We found that brigatinib potently inhibited AXL expression, and that brigatinib (0.5 µM) significantly enhanced the anti-tumor efficacy of osimertinib (1 µM) in AXL-mediated osimertinib-resistant NSCLC cell lines in vitro. We demonstrated that brigatinib had a potential ability to bind AXL kinase protein and further inhibit its downstream pathways in NSCLC cell lines. Furthermore, we revealed that brigatinib might decrease AXL expression through increasing K48-linked ubiquitination of AXL and promoting AXL degradation in HCC827OR cells and PC-9OR cells. In AXL-high expression osimertinib-resistant PC-9OR and HCC827OR cells derived xenograft mouse models, administration of osimertinib (10 mg·kg-1·d-1) alone for 3 weeks had no effect, and administration of brigatinib (25 mg·kg-1·d-1) alone caused a minor inhibition on the tumor growth; whereas combination of osimertinib and brigatinib caused marked tumor shrinkages. We concluded that brigatinib may be a promising clinical strategy for enhancing osimertinib efficacy in AXL-mediated osimertinib-resistant NSCLC patients.


Asunto(s)
Acrilamidas , Compuestos de Anilina , Antineoplásicos , Tirosina Quinasa del Receptor Axl , Carcinoma de Pulmón de Células no Pequeñas , Resistencia a Antineoplásicos , Receptores ErbB , Neoplasias Pulmonares , Ratones Desnudos , Compuestos Organofosforados , Inhibidores de Proteínas Quinasas , Proteínas Proto-Oncogénicas , Pirimidinas , Proteínas Tirosina Quinasas Receptoras , Animales , Femenino , Ratones , Acrilamidas/farmacología , Acrilamidas/uso terapéutico , Compuestos de Anilina/farmacología , Compuestos de Anilina/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Línea Celular Tumoral , Resistencia a Antineoplásicos/efectos de los fármacos , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Indoles , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Ratones Endogámicos BALB C , Mutación , Compuestos Organofosforados/farmacología , Compuestos Organofosforados/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Pirimidinas/farmacología , Pirimidinas/uso terapéutico , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Proteínas Tirosina Quinasas Receptoras/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
15.
Acta Pharmacol Sin ; 45(7): 1349-1365, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38504011

RESUMEN

Ischemic stroke is a major cause of disability and death worldwide, and its management requires urgent attention. Previous studies have shown that vagus nerve stimulation (VNS) exerts neuroprotection in ischemic stroke by inhibiting neuroinflammation and apoptosis. In this study, we evaluated the timing for VNS intervention in ischemic stroke, and the underlying mechanisms  of VNS-induced neuroprotection. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 60 min. The left vagus nerve at cervical level was exposed and attached to an electrode connected to a low-frequency electrical stimulator. Vagus nerve stimulation (VNS) was given for 60 min before, during and after tMCAO (Pre-VNS, Dur-VNS, Post-VNS). Neurological function was assessed 24 h after reperfusion. We found that all the three VNS significantly protected against the tMCAO-induced injury evidenced by improved neurological function and reduced infarct volume. Moreover, the Pre-VNS was the most effective against the ischemic injury. We found that tMCAO activated microglia in the ischemic core and penumbra regions of the brain, followed by the NLRP3 inflammasome activation-induced neuroinflammation, which finally triggered neuronal death. VNS treatment preserved α7nAChR expression in the penumbra regions, inhibited NLRP3 inflammasome activation and ensuing neuroinflammation, rescuing cerebral neurons. The role of α7nAChR in microglial NLRP3 inflammasome activation in ischemic stroke was further validated using genetic manipulations, including Chrna7 knockout mice and microglial Chrna7 overexpression mice, as well as pharmacological interventions using the α7nAChR inhibitor methyllycaconitine and agonist PNU-282987. Collectively, this study demonstrates the potential of VNS as a safe and effective strategy to treat ischemic stroke, and presents a new approach targeting microglial NLRP3 inflammasome, which might be therapeutic for other inflammation-related diseases.


Asunto(s)
Infarto de la Arteria Cerebral Media , Inflamasomas , Accidente Cerebrovascular Isquémico , Ratones Endogámicos C57BL , Microglía , Proteína con Dominio Pirina 3 de la Familia NLR , Estimulación del Nervio Vago , Receptor Nicotínico de Acetilcolina alfa 7 , Animales , Receptor Nicotínico de Acetilcolina alfa 7/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Estimulación del Nervio Vago/métodos , Accidente Cerebrovascular Isquémico/metabolismo , Microglía/metabolismo , Ratones , Inflamasomas/metabolismo , Masculino , Infarto de la Arteria Cerebral Media/terapia , Neuroprotección , Ratones Noqueados
16.
J Comput Assist Tomogr ; 48(1): 19-25, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37551145

RESUMEN

OBJECTIVES: Whether or not a gastric cancer (GC) patient exhibits lymph node metastasis (LNM) is critical to accurately guiding their treatment and prognostic evaluation, necessitating the ability to reliably predict preoperative LNM status. The present meta-analysis sought to examine the diagnostic value of computed tomography (CT)-based predictive models as a tool to gauge the preoperative LNM status of patients with GC. METHODS: Relevant articles were identified in the PubMed, Web of Science, and Wanfang databases. These studies were used to conduct pooled analyses examining sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) values, and area under the curve values were computed for summary receiver operating characteristic curves. RESULTS: The final meta-analysis incorporated data from 15 studies, all of which were conducted in China, enrolling 3,817 patients with GC (LNM+: 1790; LNM-: 2027). The developed CT-based predictive model exhibited respective pooled sensitivity, specificity, PLR, and NLR values of 84% (95% confidence interval [CI], 0.79-0.87), 81% (95% CI, 0.76-0.85), 4.39 (95% CI, 3.40-5.67), and 0.20 (95% CI, 0.16-0.26). The identified results were not associated with significant potential for publication bias ( P = 0.071). Similarly, CT-based analyses of LN status exhibited respective pooled sensitivity, specificity, PLR, and NLR values of 62% (95% CI, 0.53-0.70), 77% (95% CI, 0.72-0.81), 2.71 (95% CI, 2.20-3.33), and 0.49 (95% CI, 0.40-0.61), with no significant risk of publication bias ( P = 0.984). CONCLUSIONS: Overall, the present meta-analysis revealed that a CT-based predictive model may outperform CT-based analyses alone when assessing the preoperative LNM status of patients with GC, offering superior diagnostic utility.


Asunto(s)
Neoplasias Gástricas , Humanos , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/patología , Tomografía Computarizada por Rayos X , Probabilidad , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología
17.
Artículo en Inglés | MEDLINE | ID: mdl-38907791

RESUMEN

PURPOSE OF REVIEW: To explore the mechanism and therapeutic effect of sympathetic nerve regulation on neuropathic pain. RECENT FINDINGS: A comprehensive search was conducted in the PubMed and CNKI libraries, using the following keywords: stele ganglion block, neuropathic pain, sympathetic nerve block, sympathetic chemical destruction, and sympathetic radiofrequency thermocoagulation. We selected and critically reviewed research articles published in English that were related to sympathetic modulation in the treatment of neuropathic pain. The collected literature will be classified according to content and reviewed in combination with experimental results and clinical cases. Neuropathic pain was effectively treated with sympathetic regulation technology. Its mechanism includes the inhibition of sympathetic nerve activity, regulation of the inflammatory response, and inhibition of pain transmission, which greatly alleviates neuropathic pain in patients. Stellate ganglion blocks, thoracic and lumbar sympathectomies, chemical destruction, and radiofrequency thermocoagulation have been widely used to treat neuropathic pain. Sympathetic regulation can effectively relieve pain symptoms and improve the patient's quality of life by inhibiting sympathetic nerve activity, reducing the production and release of pain-related mediators, and inhibiting pain transmission. CT-guided radiofrequency thermocoagulation of the thoracic and lumbar sympathetic nerves is effective and durable, with few complications, and is recommended as a treatment for intractable neuropathic pain.

18.
World J Surg Oncol ; 22(1): 51, 2024 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-38336734

RESUMEN

BACKGROUND: Presurgical computed tomography (CT)-guided localization is frequently employed to reduce the thoracotomy conversion rate, while increasing the rate of successful sublobar resection of ground glass nodules (GGNs) via video-assisted thoracoscopic surgery (VATS). In this study, we compared the clinical efficacies of presurgical CT-guided hook-wire and indocyanine green (IG)-based localization of GGNs. METHODS: Between January 2018 and December 2021, we recruited 86 patients who underwent CT-guided hook-wire or IG-based GGN localization before VATS resection in our hospital, and compared the clinical efficiency and safety of both techniques. RESULTS: A total of 38 patients with 39 GGNs were included in the hook-wire group, whereas 48 patients with 50 GGNs were included in the IG group. There were no significant disparities in the baseline data between the two groups of patients. According to our investigation, the technical success rates of CT-based hook-wire- and IG-based localization procedures were 97.4% and 100%, respectively (P = 1.000). Moreover, the significantly longer localization duration (15.3 ± 6.3 min vs. 11.2 ± 5.3 min, P = 0.002) and higher visual analog scale (4.5 ± 0.6 vs. 3.0 ± 0.5, P = 0.001) were observed in the hook-wire patients, than in the IG patients. Occurrence of pneumothorax was significantly higher in hook-wire patients (27.3% vs. 6.3%, P = 0.048). Lung hemorrhage seemed higher in hook-wire patients (28.9% vs. 12.5%, P = 0.057) but did not reach statistical significance. Lastly, the technical success rates of VATS sublobar resection were 97.4% and 100% in hook-wire and IG patients, respectively (P = 1.000). CONCLUSIONS: Both hook-wire- and IG-based localization methods can effectively identified GGNs before VATS resection. Furthermore, IG-based localization resulted in fewer complications, lower pain scores, and a shorter duration of localization.


Asunto(s)
Neoplasias Pulmonares , Nódulos Pulmonares Múltiples , Nódulo Pulmonar Solitario , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Verde de Indocianina , Nódulo Pulmonar Solitario/diagnóstico por imagen , Nódulo Pulmonar Solitario/cirugía , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Cirugía Torácica Asistida por Video/métodos , Pulmón , Nódulos Pulmonares Múltiples/diagnóstico por imagen , Nódulos Pulmonares Múltiples/cirugía
19.
Biomed Chromatogr ; 38(7): e5873, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38587039

RESUMEN

Ziziphi Spinosae Semen (ZSS) and fried ZSS (FZSS) have been used for treating insomnia and depression in China. However, the potential influence of chemical variations on their efficacy remains unclear. This study demonstrated that compared with ZSS, FZSS exhibited an increase in the content of seven compounds, while the fatty oil content decreased. Both ZSS and FZSS exhibited antidepressive effects in a chronic unpredictable mild stress rat model, indicating a synergistic regulation of deficiencies in 5-hydroxytryptamine in the brain and the hyperactivation of severe peripheral inflammation. ZSS demonstrated a superior modulatory effect compared with FZSS, as indicated by integrated pharmacodynamic index, metabolic profile, and relative distance value. The potential mechanism underlying their antidepressive effects involved the modulation of gut microbiota structure to alleviate excessive inflammatory responses and imbalanced tryptophan metabolism. Correlation analysis indicated that the higher fatty oil contents should be comprehensively considered as the main reason for ZSS's superior antidepressive effects, achieved through the regulation of pyroglutamic acid levels.


Asunto(s)
Antidepresivos , Microbioma Gastrointestinal , Metabolómica , Ratas Sprague-Dawley , Ziziphus , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Microbioma Gastrointestinal/fisiología , Ziziphus/química , Ratas , Metabolómica/métodos , Antidepresivos/farmacología , Antidepresivos/química , Masculino , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Depresión/metabolismo , Depresión/tratamiento farmacológico , Metaboloma/efectos de los fármacos , Metaboloma/fisiología , Modelos Animales de Enfermedad
20.
Altern Ther Health Med ; 30(1): 102-110, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37773652

RESUMEN

Objective: A large proportion of patients undergoing assisted reproductive therapy (ART) suffer from premature ovarian insufficiency (POI). The knowledge structure, research hotspots, and research trends related to ART for patients with POI are still unclear and have not been systematically summarized. We aimed to analyze the research status of ART for patients with POI and deeply explore its knowledge structure and research trends. Our findings may provide treatment recommendations for clinicians and guidance for researchers in further research. Methods: The PubMed database for publications on ART for patients with POI was searched. The Bibliographic Item Co-occurrence Matrix Builder (BICOMB) obtained the Co-word matrix and co-occurrence matrix. The H-index method was used to extract high-frequency main Medical Subject Headings (MeSH) terms/subheadings. Then we used software such as graphical clustering toolkit (gCluto), Microsoft Excel, Ucinet and NetDraw to carry out the biclustering analysis, strategic diagram analysis and social network analysis of the major MeSH terms/subheadings. Results: The high-frequency major MeSH terms/subheadings were analyzed by biclustering, strategic diagram, and social network analyses. A total of 431 articles from 1983 to 2023 were retrieved. Analysis showed that a total of 176 journals published relevant papers, including FERTILITY AND STERILITY, ranking first. In addition, we extracted 20 high-frequency major MeSH terms/subheadings. We grouped them into five categories: cryopreservation of oocyte and ovarian tissue, oocyte donation, in vitro activation (IVA) of primordial follicles, overview of therapy for patients with POI, therapy of iatrogenic POI. Within these five categories, there were 4, 4, 3, 4, and 5 major MeSH terms/subheadings, respectively. The major MeSH terms/subheadings were evenly distributed, and no particular group had a particular central tendency. Conclusion: The therapy of Iatrogenic POI is in the core position of research and is becoming increasingly mature. Oocyte donation and IVA of primordial follicles are the trends of future research. This study is helpful to understand the current research status, knowledge structure, and research trends of ART for patients with POI, and provide reference for improving ART for patients with POI in the future. Our study may guide clinicians to apply more established research to treat patients, which may lead to better treatment outcomes for patients. At the same time, we also suggest that researchers can conduct research in the field of future research trends, which may lead to greater research results.


Asunto(s)
Infertilidad , Técnicas Reproductivas Asistidas , Humanos , Bibliometría , Fertilidad , Enfermedad Iatrogénica
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA