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1.
Blood Adv ; 2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34555844

RESUMO

Development of normal blood cells is often suppressed in juvenile myelomonocytic leukemia (JMML), a myeloproliferative neoplasm (MPN) of childhood, causing complications and impacting therapeutic outcomes. However, the mechanism underlying this phenomenon remains uncharacterized. To address this question, we induced the most common mutation identified in JMML (Ptpn11E76K) specifically in the myeloid lineage with hematopoietic stem cells (HSCs) spared. These mice uniformly developed a JMML-like MPN. Importantly, HSCs in the same bone marrow (BM) microenvironment were aberrantly activated and differentiated at the expense of self-renewal. As a result, HSCs lost quiescence and became exhausted. A similar result was observed in wild-type (WT) donor HSCs when co-transplanted with Ptpn11E76K/+ BM cells into WT mice. Co-culture testing demonstrated that JMML/MPN cells robustly accelerated differentiation in mouse and human normal hematopoietic stem/progenitor cells. Cytokine profiling revealed that Ptpn11E76K/+ MPN cells produced excessive IL-1ß, but not IL-6, TNF-α, IFN-γ, IL-1α, or other inflammatory cytokines. Depletion of the IL-1ß receptor effectively restored HSC quiescence, normalized their pool size, and rescued them from exhaustion in Ptpn11E76K/+/IL-1R-/- double mutant mice. These findings suggest IL-1ß signaling as a potential therapeutic target for preserving normal hematopoietic development in JMML.

2.
Biochem Cell Biol ; 99(5): 527-535, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34424795

RESUMO

This study explored the molecular mechanism behind the protective effects from low-dose lipopolysaccharide (LPS) on an in-vitro model of spinal cord injury (SCI). For this, PC12 cells were treated with different concentrations of LPS and the cell counting kit-8 assay was used to measure the toxicity of LPS to the cells. Next, we used immunofluorescence to measure nuclear translocation of Nrf2 in PC12 cells. PC12 cells were then treated with IGF-1 (PI3K agonist) and LY294002 (PI3K inhibitor). An in-vitro model of SCI was then established via oxygen-glucose deprivation/reoxygenation. Rates of apoptosis were measured using flow cytometry and the TUNEL assay. Low-dose LPS increased the expression levels of Nrf2, p-PI3K/PI3K, and p-AKT/AKT, and facilitated nuclear translocation of Nrf2. The activation of PI3K-AKT signaling by IGF-1 significantly increased the expression of Nrf2, whereas inhibition of PI3K-AKT signaling significantly decreased the expression of Nrf2. Low-dose LPS reduced the apoptotic ratio of PC12 cells, decreased the expression levels of caspase 3 and caspase 9, and increased the expression levels of HO-1, NQO1, and γ-GCS. Low-dose LPS also reduced the rate of apoptosis and oxidative stress by activating the PI3K-AKT-Nrf2 signaling pathway. Collectively, the results indicate that PI3K-AKT-Nrf2 signaling participates in the protective effects from low-dose LPS in an in-vitro PC12 cell model of SCI.

3.
J Environ Manage ; 296: 113340, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34328868

RESUMO

Artificial carbon materials (ACMs), notably hydrochar, pyrochar, and artificial humic substances, etc., are considered to be sustainable and eco-friendly materials for environmental remediation and improvement. At present, almost relevant literature mainly focuses on biochar, and it is necessary to systematically summarize and expand studies on ACMs. ACMs are widely used to solve pollution problems in water and soil environments, as well as to remediate and improve soil quality. This review focuses on the following issues: 1. Reveal the synthetic mechanisms and compositional reactions effects of the charring process; 2. Define artificial humus as a novel class of ACMs and discuss the application of environmental remediation and relative enhancement effects; 3. Research the relative mechanisms and significance of ACMs during remediation process, involving removal and fixation of heavy metal ions (HMs)/organic pollutants (OPs), modification of soil physicochemical properties, affecting microbial community effects, and improving fertility for crop growth. Finally, the cost-benefit analysis and security-risk evaluation of ACMs are pointed out.


Assuntos
Recuperação e Remediação Ambiental , Metais Pesados , Poluentes do Solo , Biomassa , Carbono , Carvão Vegetal , Metais Pesados/análise , Solo , Poluentes do Solo/análise
4.
J Environ Sci (China) ; 106: 116-123, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34210427

RESUMO

Nowadays, iron ions as a ubiquitous heavy metal pollutant are gradually concerned and the convenient and quick removal of excessive iron ions in groundwater has become a major challenge for the safety of drinking water. In this study, boron-doped biochar (B-BC) was successfully prepared at various preparation conditions with the addition of boric acid. The as-prepared material has a more developed pore structure and a larger specific surface area (up to 897.97 m²/g). A series of characterization results shows that boric acid effectively activates biochar, and boron atoms are successfully doped on biochar. Compared with the ratio of raw materials, the pyrolysis temperature has a greater influence on the amount of boron doping. Based on Langmuir model, the maximum adsorption capacity of 800B-BC1:2 at 25 °C, 40 °C, 55 °C are 50.02 mg/g, 95.09 mg/g, 132.78 mg/g, respectively. Pseudo-second-order kinetic model can better describe the adsorption process, the adsorption process is mainly chemical adsorption. Chemical complexation, ions exchange, and co-precipitation may be the main mechanisms for Fe2+ removal.


Assuntos
Poluentes Químicos da Água , Zea mays , Adsorção , Boro , Carvão Vegetal , Cinética , Poluentes Químicos da Água/análise
5.
Colloids Surf B Biointerfaces ; 207: 111996, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34298411

RESUMO

Light-induced surface potential have been demonstrated as an effective bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation regulator. However, traditional bone repair implants almost were weak or no light-responsive. Fortunately, surface modification was a feasible strategy to realize its light functionalization for bone implants. Herein, a graphene oxide (GO)/titanium dioxide (TiO2) nanodots composite coating on the surface of titanium (Ti) implant was constructed, and GO was reduced to reduced graphene oxide (rGO) with the method of UV-assisted photocatalytic reduction. After rGO deposited on the surface of TiO2, a heterojunction formed at the interface of rGO and TiO2. With visible light illumination, positive charges accumulated on the surface of rGO/TiO2 film, and performed as a positive surface potential change. The light-induced surface potential which was generated under proper light intensity is harmless to the cell adhesion and proliferation behavior, but presented a good BMSCs osteogenic differentiation promoting effect, and the activation of the voltage-gated calcium channels through surface potential and the promotion of the adsorption of osteogenic growth factors could be the reason. This work given a new insight of the modification for Ti implant with a light-induced surface potential, and shows potential application for bone regeneration on the clinical practice through light stimulation.


Assuntos
Grafite , Células-Tronco Mesenquimais , Diferenciação Celular , Osteogênese , Titânio
6.
Cell Rep ; 36(4): 109421, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34320342

RESUMO

Mitogen-activated protein kinases (MAPKs) are inactivated by dual-specificity phosphatases (DUSPs), the activities of which are tightly regulated during cell differentiation. Using knockdown screening and single-cell transcriptional analysis, we demonstrate that DUSP4 is the phosphatase that specifically inactivates p38 kinase to promote megakaryocyte (Mk) differentiation. Mechanistically, PRMT1-mediated methylation of DUSP4 triggers its ubiquitinylation by an E3 ligase HUWE1. Interestingly, the mechanistic axis of the DUSP4 degradation and p38 activation is also associated with a transcriptional signature of immune activation in Mk cells. In the context of thrombocytopenia observed in myelodysplastic syndrome (MDS), we demonstrate that high levels of p38 MAPK and PRMT1 are associated with low platelet counts and adverse prognosis, while pharmacological inhibition of p38 MAPK or PRMT1 stimulates megakaryopoiesis. These findings provide mechanistic insights into the role of the PRMT1-DUSP4-p38 axis on Mk differentiation and present a strategy for treatment of thrombocytopenia associated with MDS.

7.
J Nanobiotechnology ; 19(1): 207, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34247649

RESUMO

Metal ions have been identified as important bone metabolism regulators and widely used in the field of bone tissue engineering, however their exact role during bone regeneration remains unclear. Herein, the aim of study was to comprehensively explore the interactions between osteoinductive and osteo-immunomodulatory properties of these metal ions. In particular, the osteoinductive role of zinc ions (Zn2+), as well as its interactions with local immune microenvironment during bone healing process, was investigated in this study using a sustained Zn2+ delivery system incorporating Zn2+ into ß-tricalcium phosphate/poly(L-lactic acid) (TCP/PLLA) scaffolds. The presence of Zn2+ largely enhanced osteogenic differentiation of periosteum-derived progenitor cells (PDPCs), which was coincident with increased transition from M1 to M2 macrophages (M[Formula: see text]s). We further confirmed that induction of M2 polarization by Zn2+ was realized via PI3K/Akt/mTOR pathway, whereas marker molecules on this pathway were strictly regulated by the addition of Zn2+. Synergically, this favorable immunomodulatory effect of Zn2+ further improved the osteogenic differentiation of PDPCs induced by Zn2+ in vitro. Consistently, the spontaneous osteogenesis and pro-healing osteoimmunomodulation of the scaffolds were thoroughly identified in vivo using a rat air pouch model and a calvarial critical-size defect model. Taken together, Zn2+-releasing bioactive ceramics could be ideal scaffolds in bone tissue engineering due to their reciprocal interactions between osteoinductive and immunomodulatory characteristics. Clarification of this synergic role of Zn2+ during osteogenesis could pave the way to develop more sophisticated metal-ion based orthopedic therapeutic strategies.

8.
J Biomed Mater Res B Appl Biomater ; 109(12): 2227-2236, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34080765

RESUMO

Electrical stimulation has been proved to be critical to regulate cell behavior. But, cell behavior is also susceptible to multiple parameters of the adverse interferences such as surface current, electrochemical reaction products, and non-uniform compositions, which often occur during direct electric stimulation. To effectively prevent the adverse interferences, a novel piezoelectric poly(vinylidene fluoride-trfluoroethylene)(P(VDF-TrFE)) layer was designed to coat onto the indium tin oxide (ITO) planar microelectrode. We found the electrical stimulation was able to regulate the osteogenic differentiation of mesenchymal stem cells (MSCs) through calcium-mediated PKC signaling pathway. Meanwhile, the surface charge of the designed P(VDF-TrFE) coating layer could be easily controlled by the pre-polarization process, which was demonstrated to trigger integrin-mediated FAK signaling pathway, finally up-regulating the osteogenic differentiation of MSCs. Strikingly, the crosstalk in the downstream of the two signaling cascades further strengthened the ERK pathway activation for osteogenic differentiation of MSCs. This P(VDF-TrFE) layer coated electrical stimulation microelectrodes therefore provide a distinct strategy to manipulate multiple-elements of biomaterial surface to regulate stem cell fate commitment.

9.
J Med Chem ; 64(14): 9577-9591, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34191515

RESUMO

Chimeric antigen receptor T cell therapy has demonstrated antileukemia efficacy. However, this therapeutic approach is hampered by severe cytokine release syndrome, which is a major impediment to its widespread application in the clinic. The safety of this approach can be improved by engineering a rapid and reversible "off" or "on" safety switch for CAR-T cells. Cutting-edge investigations combining the advantages of genetic engineering and chemical technology have led to the invention of small-molecule-based safety switches for CAR-T cells. Small molecules such as FITC, folate, rimiducid, rapamycin, proteolysis-targeting chimera (PROTAC) compounds, and dasatinib are being investigated to design such safety switches. Optimized CAR-T cells may have enhanced therapeutic efficiency with fewer adverse effects. Herein we summarize and classify current novel small-molecule-based safety switches for CAR-T cells that aim to provide pharmacological control over the activities and toxicities associated with CAR-T cell-based cancer immunotherapies.


Assuntos
Antineoplásicos/uso terapêutico , Imunoterapia Adotiva , Leucemia/terapia , Bibliotecas de Moléculas Pequenas/uso terapêutico , Humanos , Estrutura Molecular
10.
J Virol ; 95(17): e0081621, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34133900

RESUMO

The complete eradication of human immunodeficiency virus type 1 (HIV-1) is blocked by latent reservoirs in CD4+ T cells and myeloid lineage cells. Toll-like receptors (TLRs) can induce the reversal of HIV-1 latency and trigger the innate immune response. To the best of our knowledge, there is little evidence showing the "killing" effect of TLR1/2 agonists but only a small "shock" potential. To identify a new approach for eradicating the HIV latent reservoir, we evaluated the effectiveness of SMU-Z1, a novel small-molecule TLR1/2 agonist, in the "shock-and-kill" strategy. The results showed that SMU-Z1 could enhance latent HIV-1 transcription not only ex vivo in peripheral blood mononuclear cells from aviremic HIV-1-infected donors receiving combined antiretroviral therapy but also in vitro in cells of myeloid-monocytic origin targeting the NF-κB and mitogen-activated protein kinase pathways. Interestingly, the activation marker CD69 was significantly upregulated in natural killer (NK) cells, B cells, and monocytes 48 h after SMU-Z1 treatment. Furthermore, SMU-Z1 was able to activate T cells without global T cell activation, as well as increasing NK cell degranulation and gamma interferon (IFN-γ) production, which further block HIV-1-infected CD4+ lymphocytes. In summary, the present study found that SMU-Z1 can both enhance HIV-1 transcription and promote NK cell-mediated inhibition of HIV-1-infected autologous CD4+ T cells. These findings indicate that the novel TLR1/2 agonist SMU-Z1 is a promising latency-reversing agent (LRA) for eradication of HIV-1 reservoirs. IMPORTANCE Multiple in vivo studies showed that many LRAs used in the shock-and-kill approach could activate viral transcription but could not induce killing effectively. Therefore, a dual-function LRA is needed for elimination of HIV-1 reservoirs. We previously developed a small-molecule TLR1/2 agonist, SMU-Z1, and demonstrated that it could upregulate NK cells and CD8+ T cells with immune adjuvant and antitumor properties in vivo. In the present study, SMU-Z1 could activate innate immune cells without global T cell activation, induce production of proinflammatory and antiviral cytokines, and enhance the cytotoxic function of NK cells. We showed that SMU-Z1 displayed dual potential ex vivo in the shock of exposure of latently HIV-1-infected cells and in the kill of clearance of infected cells, which is critical for effective use in combination with therapeutic vaccines or broadly neutralizing antibody treatments aimed at curing AIDS.


Assuntos
Antirretrovirais/farmacologia , Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/imunologia , Células Matadoras Naturais/imunologia , Receptor 1 Toll-Like/agonistas , Receptor 2 Toll-Like/agonistas , Latência Viral , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/virologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/imunologia , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/virologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/virologia , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Bibliotecas de Moléculas Pequenas/farmacologia , Carga Viral , Ativação Viral
11.
Bioorg Chem ; 114: 105043, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34120019

RESUMO

Screening a natural product library of 850 compounds yield isoliquiritigenin as an effective anti-inflammatory agent by inhibiting the production of pro-inflammatory NO induced by Pam3CSK4, while its activity accompanied by toxicity. Further studies obtained the optimized isoliquiritigenin derivative SMU-B14, which can inhibit Pam3CSK4 triggered toll-like receptor 2 (TLR2) signaling with low toxicity and high potency. Preliminary mechanism studies indicated that SMU-B14 worked through TLR2/MyD88, phosphorylation of IKKα/ß, leading to the reduce degradation of NF-κB related IKBα and p65 complex, then inhibited the production of inflammatory cytokines, such as TNF-α, IL-6, IL-1ß both in human and murine cell lines. Subsequent polarization experiments showed SMU-B14 significant reversed the polarization of M1 phenotype primary macrophage activated by Pam3CSK4in vitro, and reduced the infiltration of neutrophil and polarization of M1-type macrophage, decreased serum alanine transaminase (ALT), as a result protected liver from being injured in vivo. In summary, we obtained an optimized lead compound SMU-B14 and found it functionally blocked TLR2/MyD88/NF-κB signaling pathway to down-regulate the production of inflammatory cytokines resulted significant liver protection property.

12.
J Med Chem ; 64(11): 7371-7389, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34029463

RESUMO

The previous virtual screening of ten million compounds yielded two novel nonlipopeptide-like chemotypes as TLR2 agonists. Herein, we present the chemical optimization of our initial hit, 1-phenyl-3-(thiophen-2-yl)urea, which resulted in the identification of SMU-C80 (EC50 = 31.02 ± 1.01 nM) as a TLR2-specific agonist with a 370-fold improvement in bioactivity. Mechanistic studies revealed that SMU-C80, through TLR1/2, recruits the adaptor protein MyD88 and triggers the NF-κB pathway to release cytokines such as TNF-α and IL-1ß from human, but not murine, cells. To the best of our knowledge, it is the first species-specific TLR1/2 agonist reported until now. Moreover, SMU-C80 increased the percentage of T, B, and NK cells ex vivo and activated the immune cells, which suppressed cancer cell growth in vitro. In summary, we obtained a highly efficient and specific human TLR1/2 agonist that acts through the MyD88 and NF-κB pathway, facilitating cytokine release and the simultaneous activation of immune cells that in turn affects the apoptosis of cancer cells.


Assuntos
Desenho de Fármacos , Tioureia/análogos & derivados , Receptor 1 Toll-Like/agonistas , Receptor 2 Toll-Like/agonistas , Animais , Apoptose/efeitos dos fármacos , Citocinas/metabolismo , Humanos , Imunoterapia , Células Matadoras Naturais/citologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/metabolismo , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Neoplasias/terapia , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Tioureia/metabolismo , Tioureia/uso terapêutico , Receptor 1 Toll-Like/metabolismo , Receptor 2 Toll-Like/metabolismo
13.
Curr Top Med Chem ; 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34047259

RESUMO

Imidazole has an important five-membered aromatic heterocyclic ring, which is available widely in natural products and synthetic molecules. The special structural characteristics of imidazole ring enable it to bind with various enzymes and receptors through hydrogen bonds, coordination, ion-dipole and cation-π interactions, hydrophobic effects, and Van der Waals forces. These interactions promote several biological activities involving anti-tumor, anti-inflammatory, anti-microbial and anti-viral properties. Herein, we review and discuss the recent developments occurred in using imidazole derivatives along with their special pharmacological activities for various diseases treatment.

14.
Sci Total Environ ; 768: 145106, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33736348

RESUMO

The intervention of human in phosphorus pool seems to be a vicious circle. The rapid population growth leads to the global food shortage, which leads to the massive use of phosphate fertilizer and the continuous exploitation of phosphate rocks. With the massive loss and fixation of phosphate fertilizer in the soil, the unavailable phosphorus in the soil becomes superfluous, while the phosphate mineral resources turn to scarce. Interestingly, exogenous carbonaceous materials, notably, biochar and humic substances, have been widely used as soil conditioners in agricultural production up to date, among other actions to interfere with the balance between the different phosphate species, which offer effective roles for increasing soil available phosphorus. This article reviews the regulation mechanisms of biochar and humic substances on phosphorus availability and circulation, including improving soil physicochemical characteristics, regulating microbial community structure, and directly interacting with phosphorus to affect the fate of phosphorus in soil. Finally, the prospects for future research directions are made, and it is hoped that the review of this article can arouse people's attention to the current plight of agricultural production and provide some methods for improving the efficiency of phosphate fertilizer use in the future.


Assuntos
Substâncias Húmicas , Solo , Carvão Vegetal , Fertilizantes/análise , Humanos , Fósforo
15.
Bioresour Technol ; 328: 124825, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33609885

RESUMO

A novel functional colloid-like magnetic biochar (Col-L-MBC) with high dispersibility is prepared by the one-step method with the prepared porous biochar as the skeleton. Notably, A-HA obtained from waste biomass through hydrothermal humification (HTH) technology has rich functional groups (i.e., phenolic-OH, -COOH, etc.), which is conducive to the uniform dispersion of magnetic nanoparticles on the porous biochar skeleton, providing rich active sites for heavy metal ion removal. Interestingly, the introduction of A-HA can also lead to the formation of new iron species. Besides, A-HA coated on the surface of the magnetic substance also improves the dispersion of the magnetic biochar (Col-L-MBC) in the solution, forming a colloid-like magnetic biochar adsorbent, bringing superior removal performance for Cd2+ (maximum removal capacity up to 169.68 mg/g). Various removal mechanisms, including Cd-π interaction, complexation, ion exchange, and precipitation are introduced, making a great contribution to rapid removal performance.


Assuntos
Metais Pesados , Poluentes Químicos da Água , Adsorção , Carvão Vegetal , Coloides , Substâncias Húmicas/análise , Fenômenos Magnéticos , Poluentes Químicos da Água/análise
16.
Biomater Sci ; 9(3): 874-881, 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33236731

RESUMO

The immune response of bone implants is closely related to the interaction between macrophages and biomaterial surfaces. In this work, the polarization behavior of mouse bone marrow-derived macrophages (BMDMs), including their morphology and expression of phenotypic markers, genes and cytokines, on charged surfaces with different potential intensities was systematically explored. We found that the charged surface could effectively promote BMDM polarization, and a higher potential intensity was conducive to the upregulation of the polarization of BMDMs into the M2 phenotype. Based on the analysis of the signaling pathways involved in integrins (αMß2 and α5ß1) and the potassium ion channel (Kv1.3), a possible underlying mechanism revealed that the integrin originated signaling pathways could more dominantly regulate macrophage polarization to the M2 phenotype. The present work therefore demonstrates that the surface charge, as a physicochemical property of material surfaces, could effectively regulate macrophage polarizations, which may provide an immunoregulation view for the surface design of biomaterials.


Assuntos
Ativação de Macrófagos , Macrófagos , Animais , Citocinas/genética , Camundongos , Fenótipo , Transdução de Sinais
17.
Curr Med Chem ; 28(5): 1042-1066, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32660393

RESUMO

Flavonoids, commonly found in various plants, are a class of polyphenolic compounds having a basic structural unit of 2-phenylchromone. Flavonoid compounds have attracted much attention due to their wide biological applications. In order to facilitate further research on the biomedical application of flavonoids, we surveyed the literature published on the use of flavonoids in medicine during the past decade, documented the commonly found structures in natural flavonoids, and summarized their pharmacological activities as well as associated mechanisms of action against a variety of health disorders including chronic inflammation, cancer, cardiovascular complications and hypoglycemia. In this mini-review, we provide suggestions for further research on the biomedical applications of flavonoids.


Assuntos
Flavonoides , Neoplasias , Flavonoides/farmacologia , Humanos , Plantas
18.
J Colloid Interface Sci ; 583: 652-660, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33039862

RESUMO

Binary metal niobium oxides can offer a higher specific capacity compared to niobium pentoxide (Nb2O5) and thus are ideal anode candidates for lithium ion capacitors (LICs). However, their lower electronic conductivity limits their ability to achieve high energy and power densities. In this paper, one-dimensional (1D) copper niobate (CuNb2O6) nanowires are successfully prepared by electrospinning technology and then immobilized on two-dimensional (2D) reduced graphene oxide (rGO) nanosheets to form a unique 1D nanowire/2D nanosheet CuNb2O6/rGO structure. The 1D/2D CuNb2O6/rGO electrode exhibits a high specific capacity of 312.2 mAh g-1 at 100 mA g-1 as the anode of LICs. The proposed Li+ storage mechanism of the CuNb2O6 anode involves CuNb2O6 decomposition into lithium niobate (Li3NbO4) and copper (Cu) during the initial lithium insertion process. The intercalation-type Li3NbO4 will further serve as the host to Li+ and the inactive Cu phase will act as a conductive network for electron transportation. Furthermore, the energy density of the assembled CuNb2O6/rGO//activated carbon (CuNb2O6/rGO//AC) device could achieve a value as high as 92.1 Wh kg-1 and could thus be considered as a possible alternative electrode material for high energy and power LICs.

19.
Ann Palliat Med ; 9(5): 3418-3427, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33065792

RESUMO

BACKGROUND: The effects of electromagnetic pulse (EMP) radiation on cognitive impairment have attracted much attention, but the mechanism is still unclear. Regulation of brain-derived neurotrophic factor (BDNF) gene expression has been found to promote memory formation and neuronal survival. Isoflurane preconditioning (IP) was reported to have a neuroprotective effect. In this study, we verified the protective effect of IP against brain injury induced by EMP exposure and examined the relation of this effect with BDNF gene regulation. METHODS: Twenty-four hours before EMP exposure, rats were pretreated with 2% inhaled isoflurane for 30 minutes. At 24 hours after EMP injury, the Morris water maze test was carried out. Meanwhile, the other rats were executed and their brain tissues were used for Nissl staining, qRT-PCR, western blot and chromatin immunoprecipitation. RESULTS: The Morris water maze results showed that 2% IP improved the spatial learning and memory ability of the rats. The Nissl staining results showed 2% of IP alleviated neuronal damage. Also, we detected the mRNA and protein expression of BDNF, and 2% IP significantly increased the expression of BDNF. We also found the expression level of histone deacetylase 2 (HDAC2) was increased and that EMP exposure significantly decreased H3 acetylation, while 2% IP reversed these phenomena, individually, BDNF transcription was activated, and neurogenesis after EMP exposure was alleviated. CONCLUSIONS: Our results suggested that 2% of IP alleviates cognitive impairment induced by EMP exposure in rats. Also, the sustained elevated level of BDNF gene transcription may be an essential mechanism for stimulating neurogenesis because of the increased level of HDAC2-dependent H3 acetylation.


Assuntos
Lesões Encefálicas , Isoflurano , Animais , Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fenômenos Eletromagnéticos , Epigênese Genética , Ratos , Transcrição Genética
20.
Oxid Med Cell Longev ; 2020: 7151946, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32963699

RESUMO

Vascular endothelial senescence induced by high glucose and palmitate (HG/PA) contributes to endothelial dysfunction, which leads to diabetic cardiovascular complications. Reduction of endothelial senescence may attenuate these pathogenic processes. This study is aimed at determining whether Ginseng-Sanqi-Chuanxiong (GSC) extracts, traditional Chinese medicine, can ameliorate human aortic endothelial cell (HAEC) senescence under HG/PA-stressed conditions and further explore the underlying mechanism. We found that GSC extracts significantly increased antisenescent activity by reducing the HG/PA-induced mitochondrial ROS (mtROS) levels in senescent HAECs. GSC extracts also induced cellular mitophagy formation, which mediated the effect of GSC extracts on mtROS reduction. Apart from this, the data showed that GSC extracts stimulated mitophagy via the AMPK pathway, and upon inhibition of AMPK by pharmacological and genetic inhibitors, GSC extract-mediated mitophagy was abolished which further led to reverse the antisenescence effect. Taken together, these data suggest that GSC extracts prevent HG/PA-induced endothelial senescence and mtROS production by mitophagy regulation via the AMPK pathway. Thus, the induction of mitophagy by GSC extracts may provide a novel therapeutic candidate for cardiovascular protection in metabolic syndrome.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Senescência Celular/efeitos dos fármacos , Diabetes Mellitus/patologia , Medicamentos de Ervas Chinesas/farmacologia , Células Endoteliais/enzimologia , Células Endoteliais/patologia , Mitofagia/efeitos dos fármacos , Extratos Vegetais/farmacologia , Transdução de Sinais , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Autofagia/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Glucose/toxicidade , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Modelos Biológicos , Ácido Palmítico/toxicidade , Extratos Vegetais/química , Quinazolinonas/farmacologia , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/efeitos dos fármacos
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