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1.
Anal Chim Acta ; 1308: 342660, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38740460

RESUMEN

BACKGROUND: The research on cysteine (Cys) determination is deemed as a hot topic, since it has been reported to be connected with various physiological processes and disease prediction. However, existing Cys-responding probes may expose some defects such as long reaction time, disappointing photostability, and suboptimal sensitivity. Under such a circumstance, our team has proposed an efficient fluorescent probe with novel sensing mechanism to perfectly cope with the above-mentioned drawbacks. RESULTS: A novel cascade reaction-based probe 9-(2,2-dicyanovinyl)-2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-8-yl acrylate (DPQA) has been synthesized for the first time. Undergoing addition-cleavage and cyclization-rearrangement processes, DPQA reacts with Cys to generate an iminocoumarin product with relucent green fluorescence, namely 11-imino-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinoline-10-carbonitrile (IMC-J), and the relative fluorescence quantum yield (Φf) soars from 0.007 to 0.793. Utilizing such a mechanism, DPQA shows a superb turn-on signal (172-fold), low detection limit (4.1 nM), and wide detection range (5-6000 nM) toward Cys detection. Encouraged by the admirable sensing performance of DPQA, bioimaging of endogenous Cys has been attempted in HeLa cells with satisfactory results. Moreover, cell model of H2O2-induced oxidative stress has been established and the Cys fluctuation during this process has been inspected, elucidating how living cells confront with the eruption of reactive oxygen species (ROS) storm. SIGNIFICANCE: The probe DPQA with such an intriguing cascade responding process for Cys detection has been endowed with many merits, such as fast reaction and superior sensitivity, conducive to improving responsiveness and rendering it more suitable for further applications. Thereby, we expect that the DPQA would be an efficient tool for detecting Cys fluctuation in living cells of different physiological processes.


Asunto(s)
Cisteína , Colorantes Fluorescentes , Cisteína/análisis , Cisteína/química , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Humanos , Células HeLa , Espectrometría de Fluorescencia , Estructura Molecular , Límite de Detección
2.
Spectrochim Acta A Mol Biomol Spectrosc ; 314: 124175, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38565051

RESUMEN

Copper is an essential trace element in the human body, and its level is directly related to many diseases. While the source of copper in human body is mainly intake from food, then the detection of copper ions (Cu2+) in food becomes crucial. Here, we synthesized a novel probe (E)-3-hydroxy-2-styryl-4H-benzo[h]chromen-4-one (NSHF) and explored the binding ability of NSHF for Cu2+ using nuclear magnetic resonance hydrogen spectroscopy (1H NMR), high-resolution mass spectrometry (HRMS), Job's plot method and density functional theory (DFT). NSHF shows the advantages of fast response time, good selectivity and high sensitivity for Cu2+. The fluorescence intensity ratio (F/F0) of NSHF shows a good linear relationship with the concentration of Cu2+ and the detection limit is 0.061 µM. NSHF was successfully applied to the detection of Cu2+ in real samples. In addition, a simple and convenient Cu2+ detection platform was constructed by combining NSHF with a smartphone and a UV lamp, which can realize the rapid detection of Cu2+. This work provides an effective tool for the real-time detection of Cu2+.


Asunto(s)
Cobre , Colorantes Fluorescentes , Humanos , Cobre/análisis , Colorantes Fluorescentes/química , Espectrometría de Fluorescencia , Iones/análisis , Alimentos
3.
World J Gastroenterol ; 30(14): 2038-2058, 2024 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-38681131

RESUMEN

BACKGROUND: Acute pancreatitis (AP) encompasses a spectrum of pancreatic inflammatory conditions, ranging from mild inflammation to severe pancreatic necrosis and multisystem organ failure. Given the challenges associated with obtaining human pancreatic samples, research on AP predominantly relies on animal models. In this study, we aimed to elucidate the fundamental molecular mechanisms underlying AP using various AP models. AIM: To investigate the shared molecular changes underlying the development of AP across varying severity levels. METHODS: AP was induced in animal models through treatment with caerulein alone or in combination with lipopolysaccharide (LPS). Additionally, using Ptf1α to drive the specific expression of the hM3 promoter in pancreatic acinar cells transgenic C57BL/6J- hM3/Ptf1α(cre) mice were administered Clozapine N-oxide to induce AP. Subsequently, we conducted RNA sequencing of pancreatic tissues and validated the expression of significantly different genes using the Gene Expression Omnibus (GEO) database. RESULTS: Caerulein-induced AP showed severe inflammation and edema, which were exacerbated when combined with LPS and accompanied by partial pancreatic tissue necrosis. Compared with the control group, RNA sequencing analysis revealed 880 significantly differentially expressed genes in the caerulein model and 885 in the caerulein combined with the LPS model. Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Set Enrichment Analysis indicated substantial enrichment of the TLR and NOD-like receptor signaling pathway, TLR signaling pathway, and NF-κB signaling pathway, alongside elevated levels of apoptosis-related pathways, such as apoptosis, P53 pathway, and phagosome pathway. The significantly elevated genes in the TLR and NOD-like receptor signaling pathways, as well as in the apoptosis pathway, were validated through quantitative real-time PCR experiments in animal models. Validation from the GEO database revealed that only MYD88 concurred in both mouse pancreatic tissue and human AP peripheral blood, while TLR1, TLR7, RIPK3, and OAS2 genes exhibited marked elevation in human AP. The genes TUBA1A and GADD45A played significant roles in apoptosis within human AP. The transgenic mouse model hM3/Ptf1α(cre) successfully validated significant differential genes in the TLR and NOD-like receptor signaling pathways as well as the apoptosis pathway, indicating that these pathways represent shared pathological processes in AP across different models. CONCLUSION: The TLR and NOD receptor signaling pathways play crucial roles in the inflammatory progression of AP, notably the MYD88 gene. Apoptosis holds a central position in the necrotic processes of AP, with TUBA1A and GADD45A genes exhibiting prominence in human AP.


Asunto(s)
Ceruletida , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Lipopolisacáridos , Ratones Endogámicos C57BL , Ratones Transgénicos , Páncreas , Pancreatitis , Factores de Transcripción , Animales , Ceruletida/toxicidad , Ratones , Pancreatitis/genética , Pancreatitis/inducido químicamente , Pancreatitis/patología , Pancreatitis/metabolismo , Perfilación de la Expresión Génica/métodos , Páncreas/patología , Páncreas/metabolismo , Humanos , Transcriptoma , Masculino , Transducción de Señal , Células Acinares/metabolismo , Células Acinares/patología
4.
J Pharm Anal ; 14(4): 100905, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38665224

RESUMEN

Epigenomic imbalance drives abnormal transcriptional processes, promoting the onset and progression of cancer. Although defective gene regulation generally affects carcinogenesis and tumor suppression networks, tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes, which may have significant implications for the development and application of epigenetic therapy, cancer immunotherapy, and their combinations. Herein, we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes, DNA methylation, histone post-translational modification, and chromatin structure in tumor immunogenicity, and introduce these epigenetic research methods. We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immunotherapy through the complex interaction between cancer epigenetics and cancer immunology.

5.
Spectrochim Acta A Mol Biomol Spectrosc ; 315: 124288, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38636427

RESUMEN

Realizing the accurate recognition and quantification of heavy metal ions is pivotal but challenging in the environmental, biological, and physiological science fields. In this work, orange fluorescence emitting quantum dots (OQDs) have been facilely synthesized by one-step method. The participation of silver ion (Ag+) can evoke the unique aggregation-induced emission (AIE) of OQDs, resulting in prominent fluorescence enhancement, which is scarcely reported previously. Moreover, the Ag+-triggered turn-on fluorescence can be continuously shut down by mercury ion (Hg2+). This intriguing sequential fluorescence variation exhibits great sensing potency for discrimination and quantification of Ag+ and Hg2+. Meanwhile, our OQDs also exhibit good selectivity, sensitivity, and rapid response toward Ag+ and Hg2+ detection. Due to their high performance, OQDs have been applied to the determination of Ag+ and Hg2+ levels in daily necessities and water samples with satisfactory results. Moreover, a portable smartphone-assisted sensing platform based on chromatic change has been constructed, facilitating the real-time and naked-eye visualization in the resource-confined scene. We anticipate that the discovery of these OQDs would be advantageous for exploring novel QDs materials for fluorescence detection.

6.
Eur J Med Chem ; 271: 116435, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38648728

RESUMEN

Multiple myeloma (MM), a cancer of plasma cells, is the second most common hematological malignancy which is characterized by aberrant plasma cells infiltration in the bone marrow and complex heterogeneous cytogenetic abnormalities. Over the past two decades, novel treatment strategies such as proteasome inhibitors, immunomodulators, and monoclonal antibodies have significantly improved the relative survival rate of MM patients. However, the development of drug resistance results in the majority of MM patients suffering from relapse, limited treatment options and uncontrolled disease progression after relapse. There are urgent needs to develop and explore novel MM treatment strategies to overcome drug resistance and improve efficacy. Here, we review the recent small molecule therapeutic strategies for MM, and introduce potential new targets and corresponding modulators in detail. In addition, this paper also summarizes the progress of multi-target inhibitor therapy and protein degradation technology in the treatment of MM.


Asunto(s)
Antineoplásicos , Resistencia a Antineoplásicos , Mieloma Múltiple , Bibliotecas de Moléculas Pequeñas , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/patología , Humanos , Resistencia a Antineoplásicos/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Inhibidores de Proteasoma/farmacología , Inhibidores de Proteasoma/química , Inhibidores de Proteasoma/uso terapéutico , Estructura Molecular
7.
J Agric Food Chem ; 72(17): 10097-10105, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38630689

RESUMEN

With the booming development of food manufacturing, developing ideal analytical tools to precisely quantify food additives is highly sought after in the food science field. Herein, a new series of quinoline-derived multifunctional fluorescent probes has been synthesized. Bearing double reactive sites, these compounds display fluorescence response toward both bisulfite (HSO3-) and hypochlorous acid (HClO). Among these compact structures, compound ethyl-2-cyano-3-(6-(methylthio)quinolin-2-yl)acrylate (QTE) was screened out. Probe QTE not only shows ratiometric variation toward HSO3- with little cross talk but also performs turn-off signal toward HClO. In addition, probe QTE has been utilized for bioimaging of HClO in living cells. Furthermore, the HSO3- content in dried food samples has been appraised by QTE with satisfactory results. Meanwhile, relying on the apparent chromaticity change, a flexible dark-box device has been elaborated for chromatic analysis, promoting visualization of HSO3- in the field.


Asunto(s)
Colorantes Fluorescentes , Ácido Hipocloroso , Quinolinas , Sulfitos , Colorantes Fluorescentes/química , Quinolinas/química , Ácido Hipocloroso/análisis , Humanos , Sulfitos/análisis , Sulfitos/química , Análisis de los Alimentos/métodos
9.
J Med Chem ; 67(6): 4346-4375, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38484122

RESUMEN

Over the past decades, the role of rearranged during transfection (RET) alterations in tumorigenesis has been firmly established. RET kinase inhibition is an essential therapeutic target in patients with RET-altered cancers. In clinical practice, initial efficacy can be achieved in patients through the utilization of multikinase inhibitors (MKIs) with RET inhibitory activity. However, the effectiveness of these MKIs is impeded by the adverse events associated with off-target effects. Recently, many RET-selective inhibitors, characterized by heightened specificity and potency, have been developed, representing a substantial breakthrough in the field of RET precision oncology. This Perspective focuses on the contemporary understanding of RET mutations, recent advancements in next-generation RET inhibitors, and the challenges associated with resistance to RET inhibitors. It provides valuable insights for the development of next-generation MKIs and selective RET inhibitors.


Asunto(s)
Neoplasias Pulmonares , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Proteínas Proto-Oncogénicas c-ret/genética , Medicina de Precisión , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Mutación , Neoplasias Pulmonares/tratamiento farmacológico
10.
J Med Chem ; 67(5): 4194-4224, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38442261

RESUMEN

Retinoic acid receptor-related orphan receptor γ (RORγ) acts as a crucial transcription factor in Th17 cells and is involved in diverse autoimmune disorders. RORγ allosteric inhibitors have gained significant research focus as a novel strategy to inhibit RORγ transcriptional activity. Leveraging the high affinity and selectivity of RORγ allosteric inhibitor MRL-871 (1), this study presents the design, synthesis, and characterization of 11 allosteric fluorescent probes. Utilizing the preferred probe 12h, we established an efficient and cost-effective fluorescence polarization-based affinity assay for screening RORγ allosteric binders. By employing virtual screening in conjunction with this assay, 10 novel RORγ allosteric inhibitors were identified. The initial SAR studies focusing on the hit compound G381-0087 are also presented. The encouraging outcomes indicate that probe 12h possesses the potential to function as a powerful tool in facilitating the exploration of RORγ allosteric inhibitors and furthering understanding of RORγ function.


Asunto(s)
Colorantes Fluorescentes , Células Th17 , Colorantes Fluorescentes/farmacología , Factores de Transcripción , Regulación de la Expresión Génica , Polarización de Fluorescencia , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo
11.
Respir Res ; 25(1): 134, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38500102

RESUMEN

Neu1 is a sialidase enzyme that plays a crucial role in the regulation of glycosylation in a variety of cellular processes, including cellular signaling and inflammation. In recent years, numerous evidence has suggested that human NEU1 is also involved in the pathogenesis of various respiratory diseases, including lung infection, chronic obstructive pulmonary disease (COPD), asthma, and pulmonary fibrosis. This review paper aims to provide an overview of the current research on human NEU1 and respiratory diseases.


Asunto(s)
Asma , Trastornos Respiratorios , Humanos , Neuraminidasa/genética , Inflamación
12.
Phytother Res ; 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38517014

RESUMEN

As a complementary and alternative therapy, traditional Chinese medicine (TCM) has been playing a significant role in gastric cancer treatment. Data from individual systematic reviews have not been comprehensively summarized, and the relationship between certain interventions and outcomes are ill-defined. This study aimed to analyze the advantages of TCM interventions for gastric cancer by the method of evidence mapping. We searched PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Chinese Scientific Journals Database, and Wanfang Database for systematic reviews of TCM treating gastric cancer up to December 31, 2023. We used Excel, Endnote 20, and Python software for the analysis of incorporated studies. We assessed the quality of included SRs by AMSTAR-2 and performed evidence mapping including 89 SRs, 1648 RCTs and 122,902 patients, identifying 47 types of interventions and 39 types of outcomes. From a visual overview, we displayed that most SRs reported beneficial effects in improving short- and long-term survival, myelosuppression, and immune function, even though the quality of evidence was generally low. The benefits of Brucea javanica Oil Emulsion Injection, ShenQiFuZheng Injection, XiaoAiPing, Astragalus-Containing TCM and Guben Xiaoji Therapy were found the most solid in corresponding aspects. Our findings suggest that although more rigorous clinical trials and SRs are needed to identify the precise effectiveness, integrating such evidence into clinical care of gastric cancer is expected to be beneficial.

13.
Front Surg ; 11: 1278421, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38486794

RESUMEN

Calcium sulfate and calcium sulfate-based biomaterials have been widely used in non-load-bearing bone defects for hundreds of years due to their superior biocompatibility, biodegradability, and non-toxicity. However, lower compressive strength and rapid degradation rate are the main limitations in clinical applications. Excessive absorption causes a sharp increase in sulfate ion and calcium ion concentrations around the bone defect site, resulting in delayed wound healing and hypercalcemia. In addition, the space between calcium sulfate and the host bone, resulting from excessively rapid absorption, has adverse effects on bone healing or fusion techniques. This issue has been recognized and addressed. The lack of sufficient mechanical strength makes it challenging to use calcium sulfate and calcium sulfate-based biomaterials in load-bearing areas. To overcome these defects, the introduction of various inorganic additives, such as calcium carbonate, calcium phosphate, and calcium silicate, into calcium sulfate is an effective measure. Inorganic materials with different physical and chemical properties can greatly improve the properties of calcium sulfate composites. For example, the hydrolysis products of calcium carbonate are alkaline substances that can buffer the acidic environment caused by the degradation of calcium sulfate; calcium phosphate has poor degradation, which can effectively avoid the excessive absorption of calcium sulfate; and calcium silicate can promote the compressive strength and stimulate new bone formation. The purpose of this review is to review the poor properties of calcium sulfate and its complications in clinical application and to explore the effect of various inorganic additives on the physicochemical properties and biological properties of calcium sulfate.

14.
Int J Mol Sci ; 25(5)2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38473715

RESUMEN

In female mammals, the proliferation and apoptosis of granulosa cells (GCs) have been shown to determine the fate of follicles. DNA methyltransferases (DNMTs) and SLCO3A1 have been reported to be involved in the survival of GCs and follicular growth. However, the molecular mechanisms enabling DNMTs to regulate the expression of SLCO3A1 to participate in follicular growth are unclear. In this study, we found that the knockdown of DNMT1 enhanced the mRNA and protein levels of SLCO3A1 by regulating the chromatin accessibility probably. Moreover, SLCO3A1 upregulated the mRNA and protein levels of MCL1, PCNA, and STAR to promote the proliferation of GCs and facilitated cell cycle progression by increasing the mRNA and protein levels of CCNE1, CDK2, and CCND1, but it decreased apoptosis by downregulating the mRNA and protein levels of CASP3 and CASP8. Moreover, SLCO3A1 promoted the growth of porcine follicles and development of mice follicles. In conclusion, the knockdown of DNMT1 upregulated the mRNA and protein levels of SLCO3A1, thereby promoting the proliferation of GCs to facilitate the growth and development of ovarian follicles, and these results provide new insights into investigations of female reproductive diseases.


Asunto(s)
Células de la Granulosa , Folículo Ovárico , Ratones , Femenino , Porcinos , Animales , Células de la Granulosa/metabolismo , Folículo Ovárico/metabolismo , Proliferación Celular/genética , Mamíferos/genética , ARN Mensajero/genética
15.
Mikrochim Acta ; 191(3): 159, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38411763

RESUMEN

Hundreds of thousands of people dying from the abuse of fentanyl and its analogs. Hence, the development of an efficient and highly accurate detection method is extremely relevant and challenging. Therefore, we proposed the introduction of oxygen defects into Fe2(MoO4)3 nanoparticles for improving the catalyst performance and combining it with multi-walled carbon nanotubes (MWCNTs) for electrochemical detection of fentanyl and its analogs. Oxygen vacancy-rich Fe2(MoO4)3 (called r-Fe2(MoO4)3) nanoparticles were successfully synthesized and characterized in detail by scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive spectrometry (EDS), X-ray diffraction (XRD), Fourier transform infrared (FT-IR), Raman spectra, BET, X-ray photoelectron spectroscopy (XPS), and electron paramagnetic resonance (EPR) and investigated by comparison with oxygen vacancy-poor Fe2(MoO4)3 (called p-Fe2(MoO4)3). The obtained oxygen vacancy-rich Fe2(MoO4)3 was ultrasonically composited with MWCNTs for modification of glassy carbon electrodes (GCEs) used for the electrochemical detection of fentanyl and its analogs. The modified MWCNT-GCE showed ultrasensitivity to fentanyl, sufentanil, alfentanil, and acetylfentanyl with limits of detection (LOD) of 0.006 µmol·L-1, 0.008 µmol·L-1, 0.018 µmol·L-1, and 0.024 µmol·L-1, respectively, and could distinguish among the four drugs based on their peak voltages. Besides, the obtained r-Fe2(MoO4)3/MWCNT composite also exhibited high repeatability, selectivity, and stability. It showed satisfactory detection performance on real samples, with recoveries of 70.53 ~ 94.85% and 50.98 ~ 82.54% in serum and urine for the four drugs in a concentration range 0.2 ~ 1 µM, respectively. The experimental results confirm that the introduction of oxygen vacancies effectively improves the sensitivity of fentanyl electrochemical detection, and this work provides some inspiration for the development of catalytic materials for electrochemical sensors with higher sensitivity.

16.
Spectrochim Acta A Mol Biomol Spectrosc ; 311: 123993, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38340447

RESUMEN

The considerable risk posed by Au3+ residues to the environment and human health has sparked interest in researching Au3+ monitoring techniques. The detection results in the usual ratio mode are more reliable. In this work, we develop a dual-mode strategy based on reducing carbon dots coupling with two-signal ratiometric and colorimetric methods for high-sensitivity, good-selectivity, and wide-range detection of Au3+. Cyan carbon dots (C-CDs) were synthesized by a simple and efficient one-step hydrothermal method. The C-CDs with rich amino group used m-phenylenediamine as carbon source, which made it have the potential as a reducing agent. After the addition of Au3+, Au3+ was reduced to Au0, generating stable gold nanoparticles (AuNPs). The fluorescence signal (F490) of C-CDs decreased. At the same time, the large size of AuNPs enhances the second-order scattering signal (S770) and produces the UV-visible absorption peak of AuNPs. Therefore, the dual-mode sensing strategy combining S770/F490 ratiometric and colorimetric detection of Au3+ is realized with high accuracy and sensitivity. Au3+ was determined in real samples and a good recovery was obtained. The dual-mode method has good performance and practicality, so it shows great potential for environment testing in a simple and reliable way.

17.
Bioorg Med Chem ; 100: 117631, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38330848

RESUMEN

Acute myeloid leukemia (AML) is the most common type of blood cancer and has been strongly correlated with the overexpression of Fms-like tyrosine kinase 3 (FLT3), a member of the class III receptor tyrosine kinase family. With the emergence of FLT3 internal tandem duplication alteration (ITD) and tyrosine kinase domain (TKD) mutations, the development of FLT3 small molecule inhibitors has become an effective medicinal chemistry strategy for AML. Herein, we have designed and synthesized two series of 1H-pyrrolo[2,3-b]pyridine derivatives CM1-CM24, as FLT3 inhibitors based on F14, which we previously reported, that can target the hydrophobic FLT3 back pocket. Among these derivates, CM5 showed significant inhibition of FLT3 and FLT3-ITD, with inhibitory percentages of 57.72 % and 53.77 % respectively at the concentration of 1 µΜ. Furthermore, CM5 demonstrated potent inhibition against FLT3-dependent human AML cell lines MOLM-13 and MV4-11 (both harboring FLT3-ITD mutant), with IC50 values of 0.75 µM and 0.64 µM respectively. In our cellular mechanistic studies, CM5 also effectively induces apoptosis by arresting cell cycle progression in the G0/G1 phase. In addition, the amide and urea linker function were discussed in detail based on computational simulations studies. CM5 will serve as a novel lead compound for further structural modification and development of FLT3 inhibitors specifically targeting AML with FLT3-ITD mutations.


Asunto(s)
Leucemia Mieloide Aguda , Tirosina Quinasa 3 Similar a fms , Humanos , Apoptosis , Línea Celular Tumoral , Tirosina Quinasa 3 Similar a fms/antagonistas & inhibidores , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/metabolismo , Mutación , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Piridinas/farmacología
18.
Phys Chem Chem Phys ; 26(7): 6196-6207, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38305020

RESUMEN

The plasmonic photothermal conversion efficiency can be enhanced by coupling among plasmonic atoms or plasmonic molecules due to the amplified local electric field and extinction cross-section. Recently, it has been theoretically proved that hybridization between dipolar modes and higher order modes can provide higher enhancement than that among dipolar modes in terms of both near- and far-field, which may lead to a higher photothermal conversion rate. In this work, we systematically investigated the photothermal conversion enhancement of plasmonic coupling between a dipolar mode of a titanium nitride nanoparticle (TiN NP) and a higher order mode of a gold nanorod (Au NR), which was compared to that of coupling among TiN NPs' dipolar modes. We evaluated the photothermal conversion efficiency of dipole-dipole coupling and dipole-multipole coupling in the nanocluster under the illumination of a monochromatic laser of 808 nm wavelength and simulated solar light, respectively. Both experimental tests and numerical simulations suggested that the plasmonic dipole-multipole coupling exhibited higher enhancement in photothermal conversion than dipole-dipole plasmonic coupling.

19.
Anal Chim Acta ; 1288: 342173, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38220304

RESUMEN

BACKGROUND: Hydrazine (N2H4) is a highly toxic and versatile chemical raw material, which poses a serious threat to the environment and human health when used in large quantities. However, the traditional methods for the detection of N2H4 have the disadvantages of time-consuming, complicated operation and expensive instruments. In contrast, fluorescence probes have many advantages, such as simple operation, high sensitivity, good selectivity, and fast response time. Therefore, there is an urgent need for a fluorescence probe that can rapidly and accurately detect the presence of N2H4 and monitor the changes in its concentration. RESULTS: For this purpose, we designed and synthesized a series of myricetin fluorescence probes 3-(substituent group)-5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxy. phenyl)-4H-chromen-4-one (Myr-R) for N2H4 detection. In the presence of N2H4, the probe 5,7-dimethoxy-3-(2,3,4,5,6-pentafluorobenzoate)-2-(3,4,5-trimethoxyphen-yl). -4H-chr-omen-4-one (Myr-3) shows significant fluorescence changes, double emission properties and a large Stokes shift (183 nm), and exhibits high selectivity and sensitivity to N2H4 (The detection limit is 93 nM). Importantly, the qualitative and quantitative analysis of N2H4 in water, soil, and air can be accomplished using fluorescence, smartphone, and UV lamps coupled with Myr-3. In addition, Myr-3 can be used for monitoring and imaging intracellular N2H4. Meanwhile, the fluorophore 3-hydroxy-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-benzopyran-4-one (Myr-Me) was applied to fingerprinting of different substrate materials due to the fact that it exhibits strong yellow fluorescence emission in the solid state and shows excellent contrast and high resolution. SIGNIFICANCE: The probe Myr-3 is not only able to rapidly detect N2H4 in complex environments, but also can be used for imaging intracellular N2H4. In addition, the fluorophore Myr-Me can be used as an effective imaging agent for visual fingerprinting. These properties enable the probe Myr-3 and the fluorophore Myr-Me for a wide range of potential applications in related fields.


Asunto(s)
Flavonoides , Agua , Humanos , Células HeLa , Agua/química , Hidrazinas/análisis , Colorantes Fluorescentes/química , Espectrometría de Fluorescencia/métodos
20.
J Orthop Surg Res ; 19(1): 7, 2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38166951

RESUMEN

BACKGROUND: The interbody fusion apparatus is a key component of the operation and plays a key role in the postoperative efficacy. Cage subsidence is one of the common complications after lumbar fusion and internal fixation. Clinical studies on the risk factors of cage subsidence are incomplete and inaccurate, especially paravertebral muscle atrophy and intervertebral bone fusion time. METHODS: Among the patients who underwent PLIF surgery in our hospital from January 2016 to January 2019, 30 patients with cage subsidence and 30 patients without cage subsidence were randomly selected to be included in this study. The differences between the two groups were compared, and the relevant factors of cage subsidence were explored by single factor comparison and multiple logistic regression analysis. RESULTS: Bone mineral density (T) of the subsidence group [(- 1.84 ± 1.81) g/cm2 vs (- 0.87 ± 1.63) g/cm2, P = 0.018] was significantly lower than that of the normal group. There were 4 patients with end plate injury in the subsidence group (P = 0.038). Preoperative end plate Modic changes [I/II/III, (7/2/2) vs (2/5/8), P = 0.043] were significantly different between the two groups. In the subsidence group, preoperative rCSA of psoas major muscle [(1.43 ± 0.40) vs (1.64 ± 0.41), P = 0.043], CSA of paravertebral muscle [(4530.25 ± 776.55) mm2 vs (4964.75 ± 888.48) mm2, P = 0.047], paravertebral muscle rCSA [(3.03 ± 0.72) vs (3.84 ± 0.73), P < 0.001] and paravertebral muscle rFCSA [(2.29 ± 0.60) vs (2.89 ± 0.66), P < 0.001] were significantly lower than those in normal group. In the subsidence group, the vertebral body area [(1547.81 ± 309.89) mm2 vs (1326.48 ± 297.21) mm2, P = 0.004], the height of the immediately corrected vertebral space [(2.86 ± 1.10) mm vs (1.65 ± 1.02) mm, P = 0.020], immediately SL corrective Angle [(5.81 + 4.71)° vs (3.24 + 3.57) °, P = 0.009), postoperative PI-LL [(11.69 + 6.99)° vs (6.66 + 9.62) °, P = 0.029] and intervertebral fusion time [(5.38 ± 1.85) months vs (4.30 ± 1.49) months, P = 0.023] were significantly higher than those in the normal group. Multivariate logistic regression analysis showed that the time of intervertebral fusion (OR = 1.158, P = 0.045), the height of immediate intervertebral space correction (OR = 1.438, P = 0.038), and the Angle of immediate SL correction (OR = 1.101, P = 0.019) were the risk factors for cage subsidence. Bone mineral density (OR = 0.544, P = 0.016) and preoperative paravertebral muscle rFCSA (OR = 0.525, P = 0.048) were protective factors. CONCLUSION: Intervertebral fusion time, correctable height of intervertebral space, excessive Angle of immediate SL correction, bone mineral density and preoperative paravertebral muscle rFCSA are risk factors for cage subsidence after PLIF.


Asunto(s)
Fusión Vertebral , Humanos , Resultado del Tratamiento , Fusión Vertebral/efectos adversos , Región Lumbosacra , Articulaciones , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Estudios Retrospectivos
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