Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 27
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Nat Commun ; 15(1): 2526, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38514666

RESUMO

ß-Cell dysfunction and ß-cell loss are hallmarks of type 2 diabetes (T2D). Here, we found that trimethylamine N-oxide (TMAO) at a similar concentration to that found in diabetes could directly decrease glucose-stimulated insulin secretion (GSIS) in MIN6 cells and primary islets from mice or humans. Elevation of TMAO levels impairs GSIS, ß-cell proportion, and glucose tolerance in male C57BL/6 J mice. TMAO inhibits calcium transients through NLRP3 inflammasome-related cytokines and induced Serca2 loss, and a Serca2 agonist reversed the effect of TMAO on ß-cell function in vitro and in vivo. Additionally, long-term TMAO exposure promotes ß-cell ER stress, dedifferentiation, and apoptosis and inhibits ß-cell transcriptional identity. Inhibition of TMAO production improves ß-cell GSIS, ß-cell proportion, and glucose tolerance in both male db/db and choline diet-fed mice. These observations identify a role for TMAO in ß-cell dysfunction and maintenance, and inhibition of TMAO could be an approach for the treatment of T2D.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Masculino , Animais , Camundongos , Camundongos Endogâmicos C57BL , Glucose/farmacologia , Metilaminas/farmacologia , Transdução de Sinais , Insulina/farmacologia
2.
Nanomicro Lett ; 16(1): 134, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38411757

RESUMO

The remarkable properties of carbon nanotubes (CNTs) have led to promising applications in the field of electromagnetic interference (EMI) shielding. However, for macroscopic CNT assemblies, such as CNT film, achieving high electrical and mechanical properties remains challenging, which heavily depends on the tube-tube interactions of CNTs. Herein, we develop a novel strategy based on metal-organic decomposition (MOD) to fabricate a flexible silver-carbon nanotube (Ag-CNT) film. The Ag particles are introduced in situ into the CNT film through annealing of MOD, leading to enhanced tube-tube interactions. As a result, the electrical conductivity of Ag-CNT film is up to 6.82 × 105 S m-1, and the EMI shielding effectiveness of Ag-CNT film with a thickness of ~ 7.8 µm exceeds 66 dB in the ultra-broad frequency range (3-40 GHz). The tensile strength and Young's modulus of Ag-CNT film increase from 30.09 ± 3.14 to 76.06 ± 6.20 MPa (~ 253%) and from 1.12 ± 0.33 to 8.90 ± 0.97 GPa (~ 795%), respectively. Moreover, the Ag-CNT film exhibits excellent near-field shielding performance, which can effectively block wireless transmission. This innovative approach provides an effective route to further apply macroscopic CNT assemblies to future portable and wearable electronic devices.

3.
J Am Chem Soc ; 146(7): 4985-4992, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38320266

RESUMO

Unsaturated amides represent common functional groups found in natural products and bioactive molecules and serve as versatile synthetic building blocks. Here, we report an iron(II)/cobalt(II) dual catalytic system for the syntheses of distally unsaturated amide derivatives. The transformation proceeds through an iron nitrenoid-mediated 1,5-hydrogen atom transfer (1,5-HAT) mechanism. Subsequently, the radical intermediate undergoes hydrogen atom abstraction from vicinal methylene by a cobaloxime catalyst, efficiently yielding ß,γ- or γ,δ-unsaturated amide derivatives under mild conditions. The efficiency of Co-mediated HAT can be tuned by varying different auxiliaries, highlighting the generality of this protocol. Remarkably, this desaturation protocol is also amenable to practical scalability, enabling the synthesis of unsaturated carbamates and ureas, which can be readily converted into various valuable molecules.

4.
J Am Chem Soc ; 146(7): 4795-4802, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38329998

RESUMO

An iron/chromium system (Fe(OAc)2, CpCr(CO)3H) catalyzes the preparation of ß,γ- or γ,δ-unsaturated amides from 1,4,2-dioxazol-5-ones. An acyl nitrenoid iron complex seems likely to be responsible for C-H activation. A cascade of three H• transfer steps appears to be involved: (i) the abstraction of H• from a remote C-H bond by the nitrenoid N, (ii) the transfer of H• from Cr to N, and (iii) the abstraction of H• from a radical substituent by the Cr•. The observed kinetic isotope effects are consistent with the proposed mechanism if nitrenoid formation is the rate-determining step. The Fe/Cr catalysts can also desaturate substituted 1,4,2-dioxazol-5-ones to 3,5-dienamides.

5.
ACS Med Chem Lett ; 14(9): 1257-1265, 2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37736168

RESUMO

Both galectin-3 and galectin-8 are involved in cell adhesion, migration, apoptosis, angiogenesis, and inflammatory processes by recognizing galactose-containing glycoproteins. Inhibiting galectin-3/8 activities is a potential treatment for cancer and tissue fibrosis. Herein, a series of novel N-arylsulfonyl-5-aryloxy-indole-2-carboxamide derivatives was disclosed as dual inhibitors toward galectin-3 and galectin-8 C-terminal domain with Kd values of low micromolar level (Cpd53, gal-3: Kd= 4.12 µM, gal-8C: Kd= 6.04 µM; Cpd57, gal-3: Kd= 12.8 µM, gal-8C: Kd= 2.06 µM), which are the most potent and selective noncarbohydrate-based inhibitors toward gal-3/8 isoforms to date. The molecular docking investigations suggested that the unique amino acids Arg144 in galectin-3 and Ser213 in galectin-8C could contribute to their potency and selectivity. The scratch wound assay demonstrated that Cpd53 and Cpd57 were able to inhibit the MRC-5 lung fibroblast cells migration as well. This class of inhibitors could serve as a new starting point for further discovering structurally distinct gal-3 and gal-8C inhibitors to be used in cancer and tissue fibrosis treatment.

6.
Nanomicro Lett ; 15(1): 106, 2023 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-37071313

RESUMO

Low-dimensional transition metal dichalcogenides (TMDs) have unique electronic structure, vibration modes, and physicochemical properties, making them suitable for fundamental studies and cutting-edge applications such as silicon electronics, optoelectronics, and bioelectronics. However, the brittleness, low toughness, and poor mechanical and electrical stabilities of TMD-based films limit their application. Herein, a TaS2 freestanding film with ultralow void ratio of 6.01% is restacked under the effect of bond-free van der Waals (vdW) interactions within the staggered 2H-TaS2 nanosheets. The restacked films demonstrated an exceptionally high electrical conductivity of 2,666 S cm-1, electromagnetic interference shielding effectiveness (EMI SE) of 41.8 dB, and absolute EMI SE (SSE/t) of 27,859 dB cm2 g-1, which is the highest value reported for TMD-based materials. The bond-free vdW interactions between the adjacent 2H-TaS2 nanosheets provide a natural interfacial strain relaxation, achieving excellent flexibility without rupture after 1,000 bends. In addition, the TaS2 nanosheets are further combined with the polymer fibers of bacterial cellulose and aramid nanofibers via electrostatic interactions to significantly enhance the tensile strength and flexibility of the films while maintaining their high electrical conductivity and EMI SE.This work provides promising alternatives for conventional materials used in EMI shielding and nanodevices.

7.
Small Methods ; 7(4): e2201694, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36802141

RESUMO

MXenes with unique physicochemical properties have shown substantial potential in electromagnetic interference (EMI) shielding. However, the chemical instability and mechanical fragility of MXenes has become a major hurdle for their application. Abundant strategies have been dedicated to improving the oxidation stability of colloidal solution or mechanical properties of films, which always come at the expense of electrical conductivity and chemical compatibility. Here, hydrogen bond (H-bond) and coordination bond are employed to achieve chemical and colloidal stability of MXenes (0.1 mg mL-1 ) by occupying the reaction sites of Ti3 C2 Tx attacking of water and oxygen molecules. Compared to the Ti3 C2 Tx , the Ti3 C2 Tx modified with alanine via H-bond shows significantly improved oxidation stability (at room temperature over 35 days), while the Ti3 C2 Tx modified with cysteine by synergy of H-bond and coordination bond can be maintained even after 120 days. Simulation and experimental results verify the formation of H-bond and Ti-S bond by a Lewis acid-base interaction between Ti3 C2 Tx and cysteine. Furthermore, the synergy strategy significantly improves the mechanical strength of the assembled film (up to 78.1 ± 7.9 MPa), corresponding the increment of 203% compared to untreated one, almost without compromising the electrical conductivity and EMI shielding performance.

8.
Hepatology ; 78(2): 562-577, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35931467

RESUMO

BACKGROUND AND AIMS: NAFLD is the most prevalent chronic liver disease worldwide and has emerged as a serious public health issue with no approved treatment. The development of NAFLD is strongly associated with hepatic lipid content, and patients with NAFLD have significantly higher rates of hepatic de novo lipogenesis (DNL) than lean individuals. Leukotriene B4 (LTB4), a metabolite of arachidonic acid, is dramatically increased in obesity and plays important role in proinflammatory cytokine production and insulin resistance. But the role of liver LTB4/LTB4 receptor 1 (Ltb4r1) in lipid metabolism is unclear. APPROACH AND RESULTS: Hepatocyte-specific knockout (HKO) of Ltb4r1 improved hepatic steatosis and systemic insulin resistance in both diet-induced and genetically induced obese mice. The mRNA level of key enzymes involved in DNL and fatty acid esterification decreased in Ltb4r1 HKO obese mice. LTB4/Ltb4r1 directly promoted lipogenesis in HepG2 cells and primary hepatocytes. Mechanically, LTB4/Ltb4r1 promoted lipogenesis by activating the cAMP-protein kinase A (PKA)-inositol-requiring enzyme 1α (IRE1α)-spliced X-box-binding protein 1 (XBP1s) axis in hepatocytes, which in turn promoted the expression of lipogenesis genes regulated by XBP1s. In addition, Ltb4r1 suppression through the Ltb4r1 inhibitor or lentivirus-short hairpin RNA delivery alleviated the fatty liver phenotype in obese mice. CONCLUSIONS: LTB4/Ltb4r1 promotes hepatocyte lipogenesis directly by activating PKA-IRE1α-XBP1s to promote lipogenic gene expression. Inhibition of hepatocyte Ltb4r1 improved hepatic steatosis and insulin resistance. Ltb4r1 is a potential therapeutic target for NAFLD.


Assuntos
Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptores do Leucotrieno B4/metabolismo , Leucotrieno B4/efeitos adversos , Leucotrieno B4/metabolismo , Camundongos Obesos , Endorribonucleases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Hepatócitos/metabolismo , Fígado/metabolismo , Obesidade/complicações , Obesidade/genética , Lipogênese/fisiologia , Dieta Hiperlipídica
9.
Small ; 19(4): e2205716, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36437045

RESUMO

Multifunctional thermal management materials with highly efficient electromagnetic wave (EMW) absorption performance are urgently required to tackle the heat dissipation and electromagnetic interference issues of high integrated electronics. However, the high thermal conductivity (λ) and outstanding EMW absorption performance are often incompatible with each other in a single material. Herein, a through-thickness arrayed NiCo2 O4 /graphene oxide/carbon fibers (NiCO@CFs) elastomer with integrated functionalities of high thermal conductivity, highly efficient EMW absorption, and excellent compressibility is reported. The NiCO@CFs elastomer realizes a high out-of-plane thermal conductivity of 15.55 W m-1  K-1 , due to the through-thickness vertically aligned CFs framework. Moreover, the unique horizontal segregated magnetic network effectively reduces the electrical contact between the CFs, which significantly enhances impedance matching of NiCO@CFs elastomer. As a result, the vertically arrayed NiCO@CFs elastomer synchronously exhibits ultrabroad effective absorption bandwidth of 8.25 GHz (9.75-18 GHz) at a thickness of 2.4 mm, good impedance matching, and a minimum reflection loss (RLmin ) of -55.15 dB. Given these outstanding findings, the multifunctional arrayed NiCO@CFs elastomer opens an avenue for applications in EMW absorption and thermal management. This strategy of constructing thermal/electrical/mechanical pathways provides a promising way for the high-performance multifunctional materials in electronic devices.

10.
Dalton Trans ; 51(31): 11620-11624, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35895115

RESUMO

A pincer iron(III) catalyst for the oxidation and chlorination of C(sp3)-H bonds was developed. Oxidation of a diagnostic substrate cis-decalin implies that a long-lived carbon-centred radical is involved. Mechanistic studies suggest that an Fe-oxo species could be responsible for the rate-determining C-H activation step. This report expands the scope of non-heme catalysts for C-H functionalisation.


Assuntos
Halogenação , Ferro , Carbono/química , Catálise , Ferro/química , Oxirredução
11.
ACS Nano ; 16(6): 9254-9266, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35674718

RESUMO

The rapid increase of operation speed, transmission efficiency, and power density of miniaturized devices leads to a rising demand for electromagnetic interference (EMI) shielding and thermal management materials in the semiconductor industry. Therefore, it is essential to improve both the EMI shielding and thermal conductive properties of commonly used polyolefin components (such as polyethylene (PE)) in electronic systems. Currently, melt compounding is the most common method to fabricate polyolefin composites, but the difficulty of filler dispersion and high resistance at the filler/filler or filler/matrix interface limits their properties. Here, a fold fabrication strategy was proposed to prepare PE composites by incorporation of a well-aligned, seamless graphene framework premodified with MXene nanosheets into the matrix. We demonstrate that the physical properties of the composites can be further improved at the same filler loading by nanoscale interface engineering: the formation of hydrogen bonds at the graphene/MXene interface and the development of a seamlessly interconnected graphene framework. The obtained PE composites exhibit an EMI shielding property of ∼61.0 dB and a thermal conductivity of 9.26 W m-1 K-1 at a low filler content (∼3 wt %, including ∼0.4 wt % MXene). Moreover, other thermoplastic composites with the same results can also be produced based on our method. Our study provides an idea toward rational design of the filler interface to prepare high-performance polymer composites for use in microelectronics and microsystems.

12.
ACS Appl Mater Interfaces ; 14(2): 3302-3314, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-34991311

RESUMO

Highly conductive polymer foam with light weight, flexibility, and high-performance electromagnetic interference (EMI) shielding is highly desired in the fields of aerospace, communication, and high-power electronic equipment, especially in the board-level packaging. However, traditional technology for preparing conductive polymer foam such as electroless plating and electroplating involves serious pollution, a complex fabrication process, and high cost. It is urgent to develop a facile method for the fabrication of highly conductive polymer foam. Herein, we demonstrated a lightweight and flexible silver-wrapped melamine foam (Ag@ME) via in situ sintering of metal-organic decomposition (MOD) at a low temperature (200 °C) on the ME skeleton modified with poly(ethylene imine). The Ag@ME with a continuous 3D conductive network exhibits good compressibility, an excellent conductivity of 158.4 S/m, and a remarkable EMI shielding effectiveness of 63 dB in the broad frequency of 8.2-40 GHz covering X-, Ku-, K-, and Ka-bands, while the volume content is only 2.03 vol %. The attenuation mechanism of Ag@ME for EM waves is systematically investigated by both EM simulation and experimental analysis. Moreover, the practical EMI shielding application of Ag@ME in board-level packaging is demonstrated and it shows outstanding near-field shielding performance. This novel strategy for fabrication of highly conductive polymer foam with low cost and non-pollution could potentially promote the practical applications of Ag@ME in the field of EMI shielding.

13.
Eur J Pharmacol ; 891: 173723, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33159933

RESUMO

Endoplasmic reticulum (ER) stress has been considered as a promising strategy in developing novel therapeutic agents for cardiovascular diseases through inhibiting cardiomyocyte apoptosis. Protocatechualdehyde (PCA) is a natural phenolic compound from medicinal plant Salvia miltiorrhiza with cardiomyocyte protection. However, the potential mechanism of PCA on cardiovascular ischemic injury is largely unexplored. Here, we found that PCA exerted markedly anti-apoptotic effect in oxygen-glucose deprivation/reoxygenation (OGD/R)-induced H9c2 cells (Rat embryonic ventricular H9c2 cardiomyocytes), which was detected by 3-(4, 5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT), lactate dehydrogenase (LDH), Hoechst 33258 and acridine orange/ethidium bromide (AO/EB) assays. PCA also obviously protected cardiomyocytes in myocardial fibrosis model of mice, which was determined by hematoxylin-eosin (HE) staining and TdT-mediated dUTP Nick-End Labeling (TUNEL) staining. Transcriptomics coupled with bioinformatics analysis revealed a complex pharmacological signaling network especially for PCA-mediated ER stress on cardiomyocytes. Further mechanism study suggested that PCA suppressed ER stress via inhibiting protein kinase R-like ER kinase (PERK), inositol-requiring enzyme1α (IRE1α), and transcription factor 6α (ATF6α) signaling pathway through Western blot, DIOC6 and ER-Tracker Red staining, leading to a protective effect against ER stress-mediated cardiomyocyte apoptosis. Taken together, our observations suggest that PCA is a major component from Salvia miltiorrhiza against cardiovascular ischemic injury by suppressing ER stress-associated PERK, IRE1α and ATF6α signaling pathways.


Assuntos
Fator 6 Ativador da Transcrição/metabolismo , Apoptose/efeitos dos fármacos , Benzaldeídos/farmacologia , Catecóis/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Endorribonucleases/metabolismo , Complexos Multienzimáticos/metabolismo , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , eIF-2 Quinase/metabolismo , Fator 6 Ativador da Transcrição/genética , Animais , Hipóxia Celular , Linhagem Celular , Modelos Animais de Doenças , Endorribonucleases/genética , Fibrose , Glucose/deficiência , Masculino , Camundongos Endogâmicos C57BL , Complexos Multienzimáticos/genética , Traumatismo por Reperfusão Miocárdica/enzimologia , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/patologia , Proteínas Serina-Treonina Quinases/genética , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Transcriptoma , eIF-2 Quinase/genética
14.
ACS Chem Neurosci ; 11(24): 4223-4230, 2020 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-33225685

RESUMO

Cerebral ischemia is accompanied by mitochondrial integrity destruction. Thus, reversion of mitochondrial damage holds great potential for cerebral ischemia therapy. As a crucial Bcl-2 family member, pro-apoptotic Bax protein is a main effector of mitochondrial permeabilization and plays an important role in mitochondrial homeostasis. However, there is still a lack of an effective cerebral protective strategy through selectively targeting Bax. In this study, we reported that natural small-molecule protosappanin A (PTA) showed a significant mitochondrial protective effect on oxygen-glucose deprivation/reperfusion (OGD/R)-induced PC12 cells injury through increasing ATP production and maintaining mitochondrial DNA (mtDNA) content. The mechanism study revealed that PTA selectively induced pro-apoptotic protein Bax degradation, without affecting other Bcl-2 family members such as Bcl-2, Bcl-xl, Bad, Puma, Bid, Bim, and Bik. In addition, we found that PTA promoted the association of autophagosomal marker LC3B to Bax for its degradation via an autophagy-dependent manner but not the ubiquitin-proteasome pathway. Collectively, our findings offered a new pharmacological strategy for maintaining mitochondrial function by inducing autophagic degradation of Bax and also provided a novel drug candidate against ischemic neuronal injury.


Assuntos
Apoptose , Mitocôndrias , Animais , Autofagia , Homeostase , Fenóis , Ratos , Proteína X Associada a bcl-2
15.
ACS Nano ; 14(10): 14134-14145, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33044056

RESUMO

Flexible and lightweight high-performance electromagnetic interference shielding materials with minimal thickness, excellent mechanical properties, and outstanding reliability are highly desired in the field of fifth-generation (5G) communication, yet remain extremely challenging to manufacture. Herein, we prepared an ultrathin densified carbon nanotube (CNT) film with superior mechanical properties and ultrahigh shielding effectiveness. Upon complete removal of impurities in pristine CNT film, charge separation in individual CNTs induced by polar molecules leads to strong CNT-CNT attraction and film densification, which significantly improve the electrical conductivity, shielding performance, and mechanical strength. The tensile strength is up to 822 ± 21 MPa, meanwhile the electrical conductivity is as high as 902,712 S/m, and the density is only 1.39 g cm-3. Notably, the shielding effectiveness is over 51 dB with a thickness of merely 1.85 µm in the broad frequency range of 4-18 GHz, and it reaches to ∼82 dB at 6.36 µm and ∼101 dB at 14.7 µm, respectively. Further, such CNT film exhibits excellent reliability after an extended period in strong acid/alkali, high temperature, and high humidity. It demonstrates the best overall performance among representative shielding materials by far, representing a critical breakthrough in the preparation of shielding film toward applications in wearable electronics and 5G communication.

16.
Theranostics ; 10(2): 797-815, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31903151

RESUMO

Background: Histone post-translational modifications (PTMs) are involved in various biological processes such as transcriptional activation, chromosome packaging, and DNA repair. Previous studies mainly focused on PTMs by directly targeting histone-modifying enzymes such as HDACs and HATs. Methods and Results: In this study, we discovered a previously unexplored regulation mechanism for histone PTMs by targeting transcription regulation factor 14-3-3ζ. Mechanistic studies revealed 14-3-3ζ dimerization as a key prerequisite, which could be dynamically induced via an allosteric effect. The selective inhibition of 14-3-3ζ dimer interaction with histone H3 modulated histone H3 PTMs by exposing specific modification sites including acetylation, trimethylation, and phosphorylation, and reprogrammed gene transcription profiles for autophagy-lysosome function and endoplasmic reticulum stress. Conclusion: Our findings demonstrate the feasibility of editing histone PTM patterns by targeting transcription regulation factor 14-3-3ζ, and provide a distinctive PTM editing strategy which differs from current histone modification approaches.


Assuntos
Proteínas 14-3-3/antagonistas & inibidores , Autofagia , Regulação da Expressão Gênica , Histonas/metabolismo , Fenóis/farmacologia , Multimerização Proteica , Processamento de Proteína Pós-Traducional , Acetilação , Regulação Alostérica , Animais , Linhagem Celular , Histonas/química , Humanos , Masculino , Metilação , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Modelos Animais , Fosforilação , Ratos , Ratos Sprague-Dawley
17.
Eur J Pharmacol ; 855: 183-191, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31082368

RESUMO

Myocardial fibrosis is associated with cardiovascular remodeling, which is characterized by abnormal collagen architecture. However, there are not yet effective strategies targeting this abnormal pathological process. The purpose of our study is to investigate the effect of protocatechualdehyde (PCA) on myocardial fibrosis for exploring the underlying target protein and molecular mechanism. We found PCA significantly suppressed isoprenaline (ISO)-induced fibrosis and collagen deposition in myocardial tissue. Then, the direct pharmacological target of PCA was identified as collagen I using cellular thermal shift assay (CETSA) coupled with stable isotope labeling with amino acids in cell culture (SILAC) technology. Surface plasmon resonance (SPR) analysis further confirmed the specific binding of PCA with collagen I. Moreover, collagen self-assembly assay and atomic force microscope analysis confirmed that PCA directly modulated collagen conformational dynamics. LC-MS/MS analysis was applied to determine lysine residues as the binding sites of PCA on collagen I by covalently cross-linking reaction. Collectively, our study suggests that PCA controls cardiovascular remodeling by mediating diffuse interstitial myocardial fibrosis. Moreover, directly targeting collagen may be a promising strategy for the treatment of heart failure and resultant myocardial fibrosis.


Assuntos
Benzaldeídos/farmacologia , Catecóis/farmacologia , Colágeno/química , Miocárdio/patologia , Animais , Linhagem Celular , Fibrose , Insuficiência Cardíaca/patologia , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Conformação Proteica/efeitos dos fármacos
18.
Front Pharmacol ; 10: 29, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30804781

RESUMO

Background: Caesalpinia sappan L. (C. sappan) is a traditional Chinese medicinal plant. The dried heartwood of C. sappan (also known as Sappan wood) has been widely used for the folkloric medical treatment of ischemic cerebral stroke in China. However, the detailed underlying pharmacological mechanism still remains largely unexplored. Methods: In this study, a middle cerebral artery occlusion (MCAO) rat model was employed to elucidate the mechanism of the anti-cerebral ischemic effects of C. sappan ethanolic extract (CEE). Moreover, systemic multi-target identification coupled with gene ontology biological process (GO BP) and reactome pathway analysis was used to investigate the potential neuroprotective mechanism. Furthermore, the presumed mechanism was confirmed through biological analysis by determining the effects of CEE on the identified signaling pathways in PC12 cells model-induced by oxygen-glucose deprivation/reperfusion (OGD/R). Results: Our study demonstrates that CEE (both through in vivo administration at a dosage of 300 mg/kg and through in vitro incubation at a dosage of 2.4 µg/mL) is a neuroprotective agent that can effectively inhibit neuronal damage, promote synaptic generation, and suppress the activation of neutrophils, microglia, and astrocytes. Moreover, the neuroprotective mechanism of CEE is mediated via regulating 150 potential target proteins, which are associated with 6 biological processes and 10 pathways, including JAK-STAT, HSP90 and DNA damage/telomere stress. Conclusion: CEE can exert neuroprotective effect through multi-target pharmacological mechanisms to prevent ischemia/reperfusion-induced cerebral injury.

19.
Nanoscale ; 10(31): 14788-14811, 2018 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-30052244

RESUMO

Motivated by the unique structure and outstanding properties of graphene, three-dimensional (3D) graphene-based polymer nanocomposites (3D-GPNCs) are considered as new generation materials for various multi-functional applications. This review presents an overview of the preparation, properties and applications of 3D-GPNCs. Three main approaches for fabricating 3D-GPNCs, namely 3D graphene based template, polymer particle/foam template, and organic molecule cross-linked graphene, are introduced. A thorough investigation and comparison of the mechanical, electrical and thermal properties of 3D-GPNCs are performed and discussed to understand their structure-property relationship. Various potential applications of 3D-GPNCs, including energy storage and conversion, electromagnetic interference shielding, oil/water separation, and sensors, are reviewed. Finally, the current challenges and outlook of these emerging 3D-GPNC materials are also discussed.

20.
Small ; 14(27): e1800534, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29847702

RESUMO

Metal-based materials with exceptional intrinsic conductivity own excellent electromagnetic interference (EMI) shielding performance. However, high density, corrosion susceptibility, and poor flexibility of the metal severely restrict their further applications in the areas of aircraft/aerospace, portable and wearable smart electronics. Herein, a lightweight, flexible, and anticorrosive silver nanowire wrapped carbon hybrid sponge (Ag@C) is fabricated and employed as ultrahigh efficiency EMI shielding material. The interconnected Ag@C hybrid sponges provide an effective way for electron transport, leading to a remarkable conductivity of 363.1 S m-1 and superb EMI shielding effectiveness of around 70.1 dB in the frequency range of 8.2-18 GHz, while the density is as low as 0.00382 g cm-3 , which are among the best performances for electrically conductive sponges/aerogels/foams by far. More importantly, the Ag@C sponge surprisingly exhibits super-hydrophobicity and strong corrosion resistance. In addition, the hybrid sponges possess excellent mechanical resilience even with a large strain (90% reversible compressibility) and an outstanding cycling stability, which is far better than the bare metallic aerogels, such as silver nanowire aerogels and copper nanowire foams. This strategy provides a facile methodology to fabricate lightweight, flexible, and anticorrosive metal-based sponge for highly efficient EMI shielding applications.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...