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1.
Angew Chem Int Ed Engl ; 63(1): e202313336, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-37983653

RESUMO

The precise control of the regioselectivity in the transition metal-catalyzed migratory hydrofunctionalization of alkenes remains a big challenge. With a transient ketimine directing group, the nickel-catalyzed migratory ß-selective hydroarylation and hydroalkenylation of alkenyl ketones has been realized with aryl boronic acids using alkyl halide as the mild hydride source for the first time. The key to this success is the use of a diphosphine ligand, which is capable of the generation of a Ni(II)-H species in the presence of alkyl bromide, and enabling the efficient migratory insertion of alkene into Ni(II)-H species and the sequent rapid chain walking process. The present approach diminishes organosilanes reductant, tolerates a wide array of complex functionalities with excellent regioselective control. Moreover, this catalytic system could also be applied to the migratory hydroarylation of alkenyl azahetereoarenes, thus providing a general approach for the preparation of 1,2-aryl heteroaryl motifs with wide potential applications in pharmaceutical discovery.

2.
Sensors (Basel) ; 23(20)2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37896629

RESUMO

Due to the strong oxidizing properties of H2O2, excessive discharge of H2O2 will cause great harm to the environment. Moreover, H2O2 is also an energetic material used as fuel, with specific attention given to its safety. Therefore, it is of great importance to explore and prepare good sensitive materials for the detection of H2O2 with a low detection limit and high selectivity. In this work, a kind of hydrogen peroxide electrochemical sensor has been fabricated. That is, polypyrrole (PPy) has been electropolymerized on the glass carbon electrode (GCE), and then Ag and Cu nanoparticles are modified together on the surface of polypyrrole by electrodeposition. SEM analysis shows that Cu and Ag nanoparticles are uniformly deposited on the surface of PPy. Electrochemical characterization results display that the sensor has a good response to H2O2 with two linear intervals. The first linear range is 0.1-1 mM (R2 = 0.9978, S = 265.06 µA/ (mM × cm2)), and the detection limit is 0.027 µM (S/N = 3). The second linear range is 1-35 mM (R2 = 0.9969, 445.78 µA/ (mM × cm2)), corresponding to 0.063 µM of detection limit (S/N = 3). The sensor reveals good reproducibility (σ = 2.104), repeatability (σ = 2.027), anti-interference, and stability. The recoveries of the electrode are 99.84-103.00% (for 0.1-1 mM of linear range) and 98.65-104.80% (for 1-35 mM linear range). Furthermore, the costs of the hydrogen peroxide electrochemical sensor proposed in this work are reduced largely by using non-precious metals without degradation of the sensing performance of H2O2. This study provides a facile way to develop nanocomposite electrochemical sensors.

3.
Acta Biomater ; 172: 454-465, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37863345

RESUMO

Ultra-high-field (UHF) MRI has shown great advantages over low-field magnetic resonance imaging (MRI). Despite being the most commonly used MRI contrast agents, gadolinium chelates perform poorly in high magnetic fields, which significantly weakens their T1 intensity. In comparison, the rare element Holmium (Ho)-based nanoparticles (NPs) have demonstrated great potential as T2-weighted MRI contrast agents in UHF MRI due to their extremely short electron relaxation times (∼ 10-13s). In this study, a multifunctional nanotherapeutic probe was designed for UHF MRI-guided chemotherapy and photothermal therapy. The Ho (III)-doped mesoporous polydopamine (Ho-MPDA, HM) nanosphere was loaded with the chemotherapeutic drug mitoxantrone (MTO) and then coated with 4T1 cell membranes to enhance active targeting delivery to breast cancer. The prepared nanotherapeutic probe MTO@HMM@4T1 (HMM@T) exhibited good biocompatibility, high drug-loading capability and great potential as Ho (III)-based UHF MRI contrast agents. Moreover, the biodegradation of HMM@T in response to the intratumor pH and glutathione (GSH) promotes MTO release. Near-infrared (NIR) light irradiation of HM induced photothermal therapy and further enhanced drug release. Consequently, HMM@T effectively acted as an MRI-guided tumor-targeting chemo-photothermal therapy against 4T1 breast cancer. STATEMENT OF SIGNIFICANCE: Ultra-high-field (UHF) MRI has shown great advantages over low-field magnetic resonance imaging (MRI). Although gadolinium chelates are the most commonly used MRI contrast agents in clinical practice, they exhibit a significantly decreased T1 relaxivity at UHF. Holmium exhibits outstanding UHF magnetic resonance capabilities in comparison with gadolinium chelates currently used in clinic. Herein, a theranostic nanodrug (HMM@T) was designed for UHF MRI-guided chemo-photothermal therapy. The nanodrug possessed remarkable UHF T2 MRI properties (r2 = 152.13 mM-1s-1) and high drug loading capability of 18.4 %. The biodegradation of HMM@T NPs under triple stimulations of pH, GSH, and NIR led to an efficient release of MTO in tumor microenvironment. Our results revealed the potential of a novel UHF MRI-guided multifunctional nanosystem in cancer treatment.


Assuntos
Neoplasias da Mama , Hipertermia Induzida , Nanopartículas , Humanos , Feminino , Hólmio/farmacologia , Terapia Fototérmica , Meios de Contraste/farmacologia , Nanomedicina Teranóstica/métodos , Gadolínio/farmacologia , Gadolínio/química , Fototerapia/métodos , Neoplasias da Mama/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Nanopartículas/química , Doxorrubicina/farmacologia , Hipertermia Induzida/métodos , Microambiente Tumoral
4.
JAMA Oncol ; 9(4): 465-472, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36821107

RESUMO

Importance: Cancers are a leading cause of mortality, accounting for nearly 10 million annual deaths worldwide, or 1 in 6 deaths. Cancers also negatively affect countries' economic growth. However, the global economic cost of cancers and its worldwide distribution have yet to be studied. Objective: To estimate and project the economic cost of 29 cancers in 204 countries and territories. Design, Setting, and Participants: A decision analytical model that incorporates economic feedback in assessing health outcomes associated with the labor force and investment. A macroeconomic model was used to account for (1) the association of cancer-related mortality and morbidity with labor supply; (2) age-sex-specific differences in education, experience, and labor market participation of those who are affected by cancers; and (3) the diversion of cancer treatment expenses from savings and investments. Data were collected on April 25, 2022. Main Outcomes and Measures: Economic cost of 29 cancers across countries and territories. Costs are presented in international dollars at constant 2017 prices. Results: The estimated global economic cost of cancers from 2020 to 2050 is $25.2 trillion in international dollars (at constant 2017 prices), equivalent to an annual tax of 0.55% on global gross domestic product. The 5 cancers with the highest economic costs are tracheal, bronchus, and lung cancer (15.4%); colon and rectum cancer (10.9%); breast cancer (7.7%); liver cancer (6.5%); and leukemia (6.3%). China and the US face the largest economic costs of cancers in absolute terms, accounting for 24.1% and 20.8% of the total global burden, respectively. Although 75.1% of cancer deaths occur in low- and middle-income countries, their share of the economic cost of cancers is lower at 49.5%. The relative contribution of treatment costs to the total economic cost of cancers is greater in high-income countries than in low-income countries. Conclusions and Relevance: In this decision analytical modeling study, the macroeconomic cost of cancers was found to be substantial and distributed heterogeneously across cancer types, countries, and world regions. The findings suggest that global efforts to curb the ongoing burden of cancers are warranted.


Assuntos
Neoplasias , Masculino , Feminino , Humanos , Morbidade , Neoplasias/epidemiologia , Neoplasias/terapia , Escolaridade , China
5.
Chem Commun (Camb) ; 58(97): 13511-13514, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36385370

RESUMO

A practical method for regioselective hydroarylation of unactivated γ- or δ-vinyl alkylamines has been reported, enabling facile preparation of highly value-added ε- or ζ-aryl alkylamines. The protocol employs nickel catalysis, shows high functional group tolerance and can be used for modifying bio-related molecules.


Assuntos
Alcenos , Níquel
6.
Chem Commun (Camb) ; 58(83): 11709-11712, 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36178252

RESUMO

A practical method for 1,2-diborylation of non-activated monosubstituted alkenes via nickel catalysis has been developed. The protocol features high functional group tolerance and can be applied for the formal synthesis of drugs and modification of natural product derivatives. Preliminary mechanistic studies imply the involvement of a Ni(II) catalytic cycle.


Assuntos
Alcenos , Produtos Biológicos , Catálise , Níquel
7.
Bioelectrochemistry ; 146: 108165, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35623273

RESUMO

L-glutamate (L-Glu) has gained much attention owing to its contribution to the umami taste and it plays important roles in the central nervous system. Herein, an enzyme-free amperometric biosensor based on a peptide possessing an electroactive ferrocene linker as ferrocene-Gly-Gly-Gly-Gly-Ile- Pro-Val-Tyr-Cys-Gly-Leu-Ile-Gly-Gly-Gly-Gly-Lys-(CH2)4- thioctic acid self- assembled on gold electrode was designed and fabricated for specific determination of L-Glu. The biosensor was characterised via cyclic voltammetry, electrochemical impedance spectroscopy, atomic force microscopy and scanning electron microscopy. The biosensor showed optimum response within 200 s at 0.10 V in phosphate-buffered saline. Moreover, the biosensor exhibited excellent sensitivity and a low detection limit of 1.00 × 10-10 M. The sensitivity at an L-Glu concentration of 1.00 × 10-7 M - 1.00 × 10-3 M was 0.1572 µA/M, and that at an L-Glu concentration of 1.00 × 10-10 M - 1.00 × 10-7 M was 0.0293 µA/M. The peptide-based biosensor had excellent specificity and a wider linear range. The relative standard deviation of the L-Glu concentrations measured by the biosensor in a hundred-fold dilution of mouse serum samples was less than 5.00% compared with the high-performance liquid chromatography results, and the recovery rate of L-Glu was from 93.32% to 105.15%.


Assuntos
Aptâmeros de Peptídeos , Ácido Glutâmico , Sequência de Aminoácidos , Animais , Metalocenos , Camundongos , Fragmentos de Peptídeos , Peptídeos , Tripsina
8.
Front Bioeng Biotechnol ; 10: 846446, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433665

RESUMO

Magnetic resonance imaging-guided high-intensity focused ultrasound (MRI-guided HIFU) is a non-invasive strategy of diagnosis and treatment that is applicable in tumor ablation. Here, we prepared a multifunctional nanotheranostic agent (SSPN) by loading perfluorohexane (PFH) and superparamagnetic iron oxides (SPIOs) in silica lipid for MRI-guided HIFU ablation of tumors. PFH was introduced to improve the ablation effect of HIFU and the ultrasound (US) contrast performance. Due to its liquid-to-gas transition characteristic, it is sensitive to temperature. SPIOs were used as an MRI contrast agent. Silica lipid was selected because it is a more stable carrier material compared with normal lipid. Previous studies have shown that SSPNs have good biocompatibility, stability, imaging, and therapeutic effects. Therefore, this system is expected to develop an important therapeutic agent for MRI-guided HIFU therapy against tumors.

9.
Adv Clin Exp Med ; 31(3): 307-315, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34856079

RESUMO

BACKGROUND: Heterogeneity within the tumor may cause large heterogeneity in quantitative perfusion parameters. Three-dimensional contrast-enhanced ultrasound (3D-CEUS) can show the spatial relationship of vascular structure after post-acquisition reconstruction and monodisperse bubbles can resonate the ultrasound pulse, resulting in the increase in sensitivity of CEUS imaging. OBJECTIVES: To evaluate whether the combination of 3D-CEUS and monodisperse microbubbles could reduce the heterogeneity of quantitative CEUS. MATERIAL AND METHODS: Three in vitro perfusion models with perfusion volume ratio of 1:2:4 were set up. Both quantitative 2D-CEUS and 3D-CEUS were used to acquire peak intensity (PI) with 2 kinds of ultrasound agents. One was a new kind of monodisperse bubbles produced in this study, named Octafluoropropane-loaded cerasomal microbubbles (OC-MBs), the other was SonoVue®. The coefficient of variation (CV) was calculated to evaluate the cross-sectional variability. Pearson's correlation analysis was used to assess the correlation between weighted PIs (average of PIs of 3 different planes) and perfusion ratios. RESULTS: The average CVs of quantitative 3D-CEUS was slightly lower than that of 2D-CEUS (0.41 ±0.17 compared to 0.55 ±0.26, p = 0.3592). As for quantitative 3D-CEUS, the PI of the OC-MBs has shown better stability than that of SonoVue®, but without a significant difference (average CVs: 0.32 ±0.19 compared to 0.50 ±0.10, p = 0.0711). In the 2D-CEUS condition, the average CVs of OC-MBs group and SonoVue® group were 0.68 ±0.15 and 0.41 ±0.17 (p = 0.2747). As for 3D-CEUS condition, using OC-MBs group and SonoVue®, the r-values of the weighted PI and perfusion ratio were 0.8685 and 0.5643, respectively, while that of 2D-CEUS condition were 0.7760 and 0.3513, respectively. CONCLUSIONS: Our in vitro experiments showed that OC-MBs have the potential in acquiring more stable quantitative CEUS value, as compared to the SonoVue® in 3D-CEUS condition. The combination of 3D-CEUS and OC-MBs can reflect perfusion volume more precisely and may be a potential way to reduce quantitative heterogeneity.


Assuntos
Meios de Contraste , Microbolhas , Estudos Transversais , Ultrassonografia/métodos
10.
Front Physiol ; 12: 763478, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34916957

RESUMO

Aims: The aim was to describe the incidence of atrial fibrillation (AF) after cavotricuspid isthmus (CTI) ablation in patients with typical atrial flutter (AFL) without history of AF and to identify risk factors for new-onset AF after the procedure. Methods: A total of 191 patients with typical AFL undergoing successful CTI ablation were enrolled. Patients who had history of AF, structural heart disease, cardiac surgery, or ablation or who received antiarrhythmic drug after procedure were excluded. Clinical and electrophysiological data were collected. Results: There were 47 patients (24.6%) developing new AF during a follow-up of 3.3 ± 1.9 years after CTI ablation. Receiver operating characteristic (ROC) curves indicated that the cut-off values of left atrial diameter (LAD) and CHA2DS2-VASc score were 42 mm and 2, with area under the curve of 0.781 and 0.550, respectively. The multivariable Cox regression analysis revealed that obstructive sleep apnea (OSA) [hazard ratio (HR) 3.734, 95% confidence interval (CI) 1.470-9.484, P = 0.006], advanced interatrial block (aIAB) (HR 2.034, 95% CI 1.017-4.067, P = 0.045), LAD > 42 mm (HR 2.710, 95% CI 1.478-4.969, P = 0.001), and CHA2DS2-VASc score > 2 (HR 2.123, 95% CI 1.118-4.034, P = 0.021) were independent risk factors of new-onset AF. Conclusion: A combination of OSA, aIAB, LAD > 42 mm, and CHA2DS2-VASc > 2 was a strongly high risk for new-onset AF after ablation for typical AFL, and it had significance in postablation management in clinical practice.

11.
Nanoscale ; 13(42): 17822-17836, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34668898

RESUMO

Near-infrared-II (NIR-II) cancer photothermal therapy (PTT) has become more and more attractive as the NIR-II light shows a higher tissue penetrating depth, which leads to better anti-cancer effects. Recently, the members of the MXene family have been reported as NIR-II photothermal agents, possessing a high specific surface area and a fascinating light-to-heat conversion rate at the same time. Herein, we reported a combination of NIR-II photothermal therapy and immune therapy based on the MXene family member niobium carbide (Nb2C). First, Nb2C nanosheets (NSs) under 50 nm were prepared. They showed a high photothermal conversion efficiency under a 1064-nm laser, and the NIR-II light showed a deeper tissue penetration depth. Then, a nanoplatform with high R837 stability and a high loading rate was obtained after modification with a polydopamine (PDA) layer on the surface of Nb2C. With the R837 modification, the percentage of mature dendritic cells (DCs) increased and the immune response enhanced, compared with the immune response caused by PTT only. Finally, a red blood cell (RBC) membrane was applied as a coat over the nanoplatform in order to avoid excessive blood clearance. During in vivo experiments, blood circulation of Nb2C@PDA-R837@RBC nanoparticles (NPs) was prolonged, and all primary tumors were eliminated. Secondary tumors were also inhibited effectively due to the strengthened immune response, proving that Nb2C@PDA-R837@RBC NPs could inhibit tumor recurrence. All the results above indicated Nb2C@PDA-R837@RBC NPs as a potential RBC camouflaged nanoplatform for the combination of effective PTT and immune therapy towards tumor treatment.


Assuntos
Hipertermia Induzida , Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Raios Infravermelhos , Nióbio , Fototerapia
12.
Org Lett ; 23(18): 7156-7160, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34468157

RESUMO

A new, simple, yet easily accessible, (1-selenocyanatoethyl)benzene has been designed and applied as a SeCN group transfer reagent for selenocyanation of aliphatic C(sp3)-H bonds for the first time. This protocol is featured with mild reaction conditions and wide substrate scope. Control experiments reveal that a radical-group transfer mechanism might be involved.

13.
Anal Bioanal Chem ; 413(25): 6343-6353, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34378069

RESUMO

A solvent-assisted ESIPT fluorescent dye was synthesized and used as a probe (2-PPN) for the detection of F-/Ag+ and high-resolution imaging of the cilia in live cells. The developed ESIPT fluorophore exhibited strong tautomeric fluorescence in protic solvents and normal emission in aprotic solvents, which is a significant departure from that of conventional intramolecular ESIPT compounds. The H-binding interaction of F- and the chelation of Ag+ with the ESIPT module of 2-PPN resulted in significant tautomeric emission quenching. From this basis, the 2-PPN-based assays for the detection of F- and Ag+ were established. The detection limit for F- and Ag+ sensing is 2.4 nM and 1.5 nM, respectively. The selective experimental results showed that no tautomeric fluorescence change of 2-PPN could be observed in the presence of the other inorganic ions in the same medium, revealing high selectivity of 2-PPN to F- and Ag+. Furthermore, MTT assay experiments proved that the probe 2-PPN exhibited low cytotoxicity and good cell membrane permeability. The probe was also further successfully utilized to image the cilia in vitro MCF7 cells, displaying its high-resolution imaging performance.Graphical abstract.


Assuntos
Cílios , Corantes Fluorescentes/síntese química , Flúor/química , Nitrilas/síntese química , Pirenos/síntese química , Prata/química , Corantes Fluorescentes/química , Humanos , Células MCF-7 , Estrutura Molecular , Nitrilas/química , Pirenos/química
14.
Adv Healthc Mater ; 10(19): e2100780, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34390223

RESUMO

Smart theragnostic nanoplatforms exhibit great promise in clinical tumor treatment. The Fe-based Fenton reaction in tumor sites may generate reactive oxygen species to kill cancer cells with negligible side effects on normal tissues. However, its efficiency and duration are limited by the low intracellular concentration of H2 O2 , weak acidicity of tumor tissue, and low catalytic activity of conventional Fenton reagents. Herein, a facile strategy is proposed to efficiently overcome these obstacles. An efficient enzymatic/Fenton-starvation nanoreactor PMs loaded with glucose oxidase and perfluoropentane (PGPMs) is constructed through synthesizing methoxy-PEG-carboxymethy-modified iron (Fe2+ /Fe3+ )-based metal-organic frameworks (PMs), followed by loading glucose oxidase (GOx) and perfluoropentane (PFP). PGPMs accumulating in the tumor tissue exhibit tumor microenvironment-responsive biodegradable behavior and unusual catalytic activity for Fenton reaction advantageous over Fe3+ -based MOFs. Meanwhile, encapsulation of GOx into PGPMs further significantly increases the catalytic activity for Fenton reaction and also induces starvation therapy. PGPMs also exhibit considerable capabilities of ultrasound and tumor microenvironment-responsive T2 MR imaging applicable for contrast-enhanced diagnosis. Both in vitro and in vivo studies demonstrate the great diagnostic and therapeutic potentials of this nanoreactor in tumor.


Assuntos
Estruturas Metalorgânicas , Neoplasias , Catálise , Glucose Oxidase , Humanos , Microambiente Tumoral
15.
Anal Methods ; 13(26): 2981-2988, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34124741

RESUMO

Fluorescence sensing organophosphorus pesticides (OPs) is of great importance for both food safety and global environment; however, the reported fluorescent probes are usually directly exposed to the external environment, resulting in premature leakage or photobleaching and thus limiting their photostability and assay sensitivity. In this work, a fluorescent sensing platform consisting of a novel luminescent metal-organic framework (Ru(bpy)32+-ZIF-90) and manganese dioxide nanosheets (MnO2 NSs) was prepared for sensing OPs. Due to the protection and improvement in the fluorescence of Ru(bpy)32+ by ZIF-90, the Ru(bpy)32+-ZIF-90 probe displayed remarkable photostability and high stability in water. By virtue of the high stability of Ru(bpy)32+-ZIF-90, as well as the outstanding fluorescence quenching and notable recognition ability of the MnO2 NSs, this sensing platform provided excellent detection capability for parathion-methyl, with a wide concentration range of 0.050-60 ng mL-1 and a low detection limit of 0.037 ng mL-1. Additionally, the system exhibited a visual color change with the concentration of the OPs under sunlight. Moreover, satisfactory recoveries ranging from 93.3% to 103.6% were obtained for the real samples. The results indicated that the Ru(bpy)32+-ZIF-90-MnO2-based OP sensing platform is promising for applications in food safety and environmental monitoring.


Assuntos
Compostos de Manganês , Praguicidas , Fluorescência , Compostos Organofosforados , Óxidos , Praguicidas/análise
16.
Org Lett ; 23(12): 4721-4725, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34080880

RESUMO

The iron-catalyzed δ-C(sp3)-H bond difluoromethylthiolation and difluoromethylselenation of aliphatic amides with high site selectivity are reported. Essential to the success is the employment of an amide radical formed in situ to activate the inert C(sp3)-H bond and the utilization of the easily handled PhSO2SCF2H and PhSO2SeCF2H as coupling reagents under mild conditions. This scalable protocol exhibits a broad substrate scope bearing versatile functional groups. Mechanistic studies indicate that the reaction proceeds through -SCF2H and -SeCF2H radical transfer.

17.
Histol Histopathol ; 36(4): 425-435, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33410125

RESUMO

OBJECTIVE: Propofol (PRO) was reported to exert a neuroprotective effect by decreasing microRNA-134 (miR-134), a brain-specific miRNA, thus, the role of PRO against cobalt chloride (CoCl2)-induced injury in rat pheochromocytoma cells (PC12) via mediating miR-134 was explored. METHODS: CoCl2-induced PC12 cells treated with PRO were transfected with or without miR-134 negative control (NC)/ inhibitor/mimic, and the following detections were then performed using cell counting kit-8 (CCK-8), Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) and Hoechst 33258 staining. Autophagy was observed by transmission electron microscope (TEM). Mitochondrial membrane potential (MMP) was detected by Rhodamine-123 (Rh123) staining, and reactive oxygen species (ROS) by dichloro-dihydro-fluorescein diacetate (DCFH-DA) staining. Protein and gene expressions were measured by Western blotting and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), respectively. RESULTS: PRO reversed the CoCl2-induced decrease in the PC12 cell viability and increased miR-134 in a dose-dependent manner. CoCl2 increased LC3II/I ratio and Beclin-1 expression, but decreased p62 expression, which was abolished by PRO. In addition, an increased cell apoptosis rates triggered by CoCl2 were reduced by PRO with the down-regulations of Bax and Caspase-3 and the up-regulation of Bcl-2. Furthermore, PRO decreased methylenedioxyamphetamine (MDA), nitric oxide (NO) and ROS in CoCl2-induced PC12 cells accompanying the increase in glutathione peroxidase (GSH-Px) and MMP. The effects of PRO on autophagy, apoptosis and oxidative stress in CoCl2-induced PC12 cell were reversed by miR-134 mimic. CONCLUSION: PRO may mitigate CoCl2-induced autophagy in PC12 cells with decreased apoptosis and improved oxidative stress via mediating miR-134.


Assuntos
Cobalto/toxicidade , MicroRNAs , Propofol/farmacologia , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , MicroRNAs/efeitos dos fármacos , MicroRNAs/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Ratos , Espécies Reativas de Oxigênio/metabolismo
18.
Anticancer Agents Med Chem ; 21(4): 508-522, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32838723

RESUMO

BACKGROUND: A Chinese folk medicine plant Pleurospermum lindleyanum possesses pharmacological activities of heat-clearing, detoxifying and preventing from hepatopathy, coronary heart disease, hypertension, and high altitude sickness. We isolated and characterized its constituents to investigate its synergistic effects against human hepatoma SMMC-7721 cells. OBJECTIVE: The aim of this study was to explore the synergistic anti-cancer activities of isolates from P. lindleyanum with 5-FU on hepatoma SMMC-7721 cells in vitro and their primary mechanisms. METHODS: Sequential chromatographic techniques were conducted for the isolation studies. The isolate's structures were established by spectroscopic analysis as well as X-ray crystallographic diffraction. Growth inhibition was detected by MTT assay. The isobologram method was used to assess the effect of drug combinations. Flow cytometry and western blot were used to examine apoptosis and protein expression. RESULTS: A new coumarin (16), along with sixteen known compounds, were isolated from the whole plant of P. lindleyanum and their structures were elucidated by spectroscopic methods. Four coumarins (2, 3, 5, and 16), two flavonoids (8 and 9) and three phytosterols and triterpenes (12-14) were found to synergistically enhance the inhibitory effect of 5-FU against SMMC-7721 cells. Among them, compounds 3 and 16 exhibited the best synergistic effects with IC50 of 5-FU reduced by 16-fold and 22-fold possessing the minimum Combination Index (CI) 0.34 and 0.27. The mechanism of action of combinations might be through synergistic arresting for the cell cycle at G1 phases and the induction of apoptosis. Moreover, western blotting and molecular docking revealed that compounds 3 or 5 might promote 5-FU-induced apoptosis by regulating the expression of Caspase 9 and PARP. CONCLUSION: Constituents from P. lindleyanum may improve the treatment effectiveness of 5-FU against hepatocellular carcinoma cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apiaceae/química , Apoptose/efeitos dos fármacos , Fluoruracila/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Fluoruracila/química , Fluoruracila/isolamento & purificação , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Tamanho da Partícula , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Relação Estrutura-Atividade
19.
Front Chem ; 8: 761, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33005609

RESUMO

To address increasingly prominent energy problems, lithium-ion batteries have been widely developed. The high-nickel type nickel-cobalt-manganese (NCM) ternary cathode material has attracted attention because of its high energy density, but it has problems such as cation mixing. To address these issues, it is necessary to start from the surface and interface of the cathode material, explore the mechanism underlying the material's structural change and the occurrence of side reactions, and propose corresponding optimization schemes. This article reviews the defects caused by cation mixing and energy bands in high-nickel NCM ternary cathode materials. This review discusses the reasons why the core-shell structure has become an optimized high-nickel ternary cathode material in recent years and the research progress of core-shell materials. The synthesis method of high-nickel NCM ternary cathode material is summarized. A good theoretical basis for future experimental exploration is provided.

20.
Talanta ; 219: 121173, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32887095

RESUMO

Sensitive and specific detection of microRNAs (miRNAs) is of great significance for early cancer diagnosis. Here we report a simple and sensitive fluorescence signal amplification strategy that based on DSN/TdT recycling digestion for miRNA detection. DSN initiates DNA digestion on 3'-phosphate-primer/miRNA heteroduplex which causes miRNA recycle. The digested DNA strands with 3'-OH ends enable TdT to synthesize a polydeoxyguanylic tails on the 3'-end. The DNAs with polydeoxyguanylic tails are converted to double-stranded-DNA prior to initiation of DSN/TdT recycling digestion. With the cooperation of TdT and DSN, a new round of digestion and extension is triggered, leading to massive fluorophores separating and signal amplification. The amplification strategy produces large amounts of 3'-OH probes that can be used directly for dsDNA enrichment and DSN digestion. Moreover, both DSN digestion and TdT extension are sequence-independent reaction without the need of complex sequences design. In addition, this strategy is utilized to analyze miRNA samples from MCF-7 cell lysates and Cu (II) ion samples, indicating its potential application in actual sample analysis. The method shows a promising analytical platform for DNA nicking-related studies and tumor biomarkers measuring in clinical diagnostics.


Assuntos
Técnicas Biossensoriais , MicroRNAs , Sondas de DNA/genética , Digestão , Humanos , MicroRNAs/genética , Técnicas de Amplificação de Ácido Nucleico
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