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1.
Molecules ; 28(19)2023 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-37836727

RESUMEN

Soot formation is an inevitable consequence of the combustion of carbonaceous fuels in environments rich in reducing agents. Efficient management of pollution in various contexts, such as industrial fires, vehicle engines, and similar applications, relies heavily on the subsequent oxidation of soot particles. Among the oxidizing agents employed for this purpose, oxygen, carbon dioxide, water vapor, and nitrogen dioxide have all demonstrated effectiveness. The scientific framework of this research can be elucidated through the following key aspects: (i) This review situates itself within the broader context of pollution management, emphasizing the importance of effective soot oxidation in reducing emissions and mitigating environmental impacts. (ii) The central research question of this study pertains to the identification and evaluation of catalysts for soot oxidation, with a specific emphasis on ceria-based catalysts. The formulation of this research question arises from the need to enhance our understanding of catalytic mechanisms and their application in environmental remediation. This question serves as the guiding principle that directs the research methodology. (iii) This review seeks to investigate the catalytic mechanisms involved in soot oxidation. (iv) This review highlights the efficacy of ceria-based catalysts as well as other types of catalysts in soot oxidation and elucidate the underlying mechanistic strategies. The significance of these findings is discussed in the context of pollution management and environmental sustainability. This study contributes to the advancement of knowledge in the field of catalysis and provides valuable insights for the development of effective strategies to combat air pollution, ultimately promoting a cleaner and healthier environment.

2.
Molecules ; 29(1)2023 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-38202648

RESUMEN

Selective oxidation of ethylbenzene to acetophenne is an important process in both organic synthesis and fine chemicals diligence. The cobalt-based catalysts combined with nitrogen-doped carbon have received great attention in ethylbenzene (EB) oxidation. Here, a series of cobalt catalysts with metallic cobalt nanoparticles (NPs) encapsulated in nitrogen-doped graphite-like carbon shells (Co@NC) have been constructed through the one-pot pyrolysis method in the presence of different nitrogen-containing compounds (urea, dicyandiamide and melamine), and their catalytic performance in solvent-free oxidation of EB with tert-butyl hydrogen peroxide (TBHP) as an oxidant was investigated. Under optimized conditions, the UCo@NC (urea as nitrogen source) could afford 95.2% conversion of EB and 96.0% selectivity to acetophenone, and the substrate scalability was remarkable. Kinetics show that UCo@NC contributes to EB oxidation with an apparent activation energy of 32.3 kJ/mol. The synergistic effect between metallic cobalt NPs and nitrogen-doped graphite-like carbon layers was obviously observed and, especially, the graphitic N species plays a key role during the oxidation reaction. The structure-performance relationship illustrated that EB oxidation was a free radical reaction through 1-phenylethanol as an intermediate, and the possible reaction mechanistic has been proposed.

3.
Chemistry ; 27(50): 12890-12899, 2021 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-34288181

RESUMEN

Chemical fixation of CO2 as C1 source at ambient temperature and low pressure is an energy-saving way to make use of the green-house gas, but it still remains a challenge since efficient catalyst with high catalytic active sites is required. Here, a novel monoclinic azo-functionalized Zr-based metal-organic polyhedron (Zr-AZDA) has been prepared and applied in CO2 fixation with epoxides. The inherent azo groups not only endow Zr-AZDA with good solubilization, but also act as basic sites to enrich CO2 showing efficient synergistic catalysis as confirmed by TPD-CO2 analysis. XPS results demonstrate that the Zr active sites in Zr-AZDA possess suitable Lewis acidity, which satisfies both substrates activation and products desorption. DFT calculation indicates the energy barrier of the rate-determining step in CO2 cycloaddition could be reduced remarkably (by ca. 60.9 %) in the presence of Zr-AZDA, which may rationalize the mild and efficient reaction condition employed (80 °C and 1 atm of CO2 ). The work provides an effective multi-functional cooperative method for improvement of CO2 cycloaddition.

4.
Chemistry ; 26(19): 4333-4340, 2020 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-31943405

RESUMEN

With the assistance of hydrogen bonds of the o-amino group, we have successfully tuned a coordination structure from a metal-organic polyhedron (MOP) to a two-dimensional (2D) metal-organic framework (MOF). The amino group forms hydrogen bonds with the two vicinal carboxylic groups, and induces the ligand to coordinate with copper ions to form the 2D structure. The obtained 2D Cu-based MOF (Cu-AIA) has been applied as an efficient heterogeneous catalyst in the aerobic epoxidation of olefins by using air as oxygen source. Without the aggregation problem of active sites in MOPs, Cu-AIA possesses much higher reactivity than MOP-1. Furthermore, the amino group of the framework has been used as a modifiable site through post-synthetic metalation (PSMet) to prepare a 2D MOF-supported Pd single-site heterogeneous catalyst, which shows excellent catalytic performance for the Suzuki reaction. It indicates that Cu-AIA can also work as a good 2D MOF carrier for the derivation of other heterogeneous catalysts.

5.
Org Biomol Chem ; 18(2): 191-204, 2020 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-31793614

RESUMEN

The ring-opening of cyclopropanols is one of the most active areas of research and it has been well documented in recent years owing to subsequent coupling with various partners, thus providing the facile syntheses of a large number of multifunctional compounds that may otherwise be difficult to access. Evidently, the useful cascade reaction requires easy access to diversely functionalized cyclopropanol substrates. However, developments in the construction of cyclopropanols have not received adequate attention. Herein, recent reports on the formation of cyclopropanols are summarized, and the highly stereoselective production of new promising substrates for the cyclopropanol ring-opening/cross-coupling reactions are introduced and improved syntheses of known cyclopropanols are depicted. This review may facilitate more interesting applications of the cyclopropanol ring-opening/coupling reaction in the synthesis of pharmaceutical compounds, natural products, and structurally more diversified organic synthetic intermediates.

6.
Beilstein J Org Chem ; 16: 1974-1982, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32831954

RESUMEN

A variety of chroman-4-ones bearing phosphine oxide motifs were conveniently synthesized from readily available diphenylphosphine oxides and alkenyl aldehydes via a metal-free tandem phosphinoylation/cyclization protocol. The reaction utilizes K2S2O8 as oxidant and proceeds in DMSO/H2O at environmentally benign conditions with a broad substrate scope and afforded the title compounds in moderate yields.

7.
J Org Chem ; 83(16): 8984-8994, 2018 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-29944369

RESUMEN

The selective construction of bicyclo[3.3.0]octan-1-ols and bicyclo[3.1.0]hexan-1-ols was achieved by using an allylSmBr/additive(s) system. By employing HMPA as the only additive, the momoallylation/ketone-alkene coupling occurred preferably and afforded bicyclo[3.3.0]octan-1-ols in good yields with high diastereoselectivities. While the ester-alkene coupling predominated to generate bicyclo[3.1.0]hexan-1-ols in moderate yields with excellent diastereoselectivities in the presence of a proton source, such as pyrrole as the coadditive with HMPA. The tunable reactivity of allylSmBr by additive(s) would make it a versatile reagent in organic synthesis.

8.
Nucleic Acids Res ; 43(18): 8898-912, 2015 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-26384563

RESUMEN

Cytokine or growth factor activated STAT3 undergoes multiple post-translational modifications, dimerization and translocation into nuclei, where it binds to serum-inducible element (SIE, 'TTC(N3)GAA')-bearing promoters to activate transcription. The STAT3 DNA binding domain (DBD, 320-494) mutation in hyper immunoglobulin E syndrome (HIES), called the HIES mutation (R382Q, R382W or V463Δ), which elevates IgE synthesis, inhibits SIE binding activity and sensitizes genes such as TNF-α for expression. However, the mechanism by which the HIES mutation sensitizes STAT3 in gene induction remains elusive. Here, we report that STAT3 binds directly to the AGG-element with the consensus sequence 'AGG(N3)AGG'. Surprisingly, the helical N-terminal region (1-355), rather than the canonical STAT3 DBD, is responsible for AGG-element binding. The HIES mutation markedly enhances STAT3 AGG-element binding and AGG-promoter activation activity. Thus, STAT3 is a dual specificity transcription factor that promotes gene expression not only via SIE- but also AGG-promoter activity.


Asunto(s)
Mutación , Regiones Promotoras Genéticas , Factor de Transcripción STAT3/genética , Activación Transcripcional , Animales , Secuencia de Bases , Sitios de Unión , Línea Celular , Secuencia de Consenso , Humanos , Síndrome de Job/genética , Ratones , Motivos de Nucleótidos , Procesamiento Proteico-Postraduccional , Factor de Transcripción STAT3/química , Factor de Transcripción STAT3/metabolismo , Factor de Necrosis Tumoral alfa/genética
9.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 37(2): 232-236, 2017 Feb.
Artículo en Zh | MEDLINE | ID: mdl-30650279

RESUMEN

Objective To observe the effect of Modified Leweiyin Recipe (MLR) on nuclear factor kappa B (NF-κB) and crosstalk between signal transducers and activators of transcription 3 (STAT3) in SGC-7901 human gastric cancer cells. Methods SGC-7901 human gastric cancer cell strain was taken as subjects. The vectors of NF-κB (ReIA/p65)-PECFP and STAT3-PEYFP were constructed and transfected in SGC-7901 human gastric cancer cells. Cells were then intervened by MLR after stimulated by LPS. The crosstalk between NF-κB and STAT3 in cells was detected using fluorescence resonance energy transfer and co-immunoprecipitation. Results After LPS stimulation, the crosstalk between NF-κB and STAT3 was enhanced. But it was significantly weakened after MLR intervention. Conclusion MLR could treat precancerous lesions of gastric cancer and prevent the occurrence of gastric cancer possibly by blocking the crosstalk between NF-κB and STAT3.


Asunto(s)
Medicamentos Herbarios Chinos , FN-kappa B , Factor de Transcripción STAT3 , Neoplasias Gástricas , Línea Celular Tumoral , Medicamentos Herbarios Chinos/farmacología , Humanos , FN-kappa B/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Neoplasias Gástricas/tratamiento farmacológico
10.
J Org Chem ; 80(1): 52-61, 2015 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-25427109

RESUMEN

In continuation of our previous study on the intramolecular reductive coupling of simple homoallylic esters promoted by allylSmBr/HMPA/H2O, which afforded a facile synthesis of 2-(2-hydroxyalkyl)cyclopropanols, here we report the reductive cascade cyclization of but-3-enyl but-3-enoates mediated by allylSmBr/HMPA/CuCl2·2H2O, in which the two C═C bonds were successively coupled to allow the construction of the structurally interesting bridged bicyclic tertiary alcohols. Thus, the 2-(2-hydroxyethyl)bicyclo[2.1.1]hexan-1-ols were prepared in moderate to good yields with excellent diastereoselectivity.


Asunto(s)
Compuestos Alílicos/química , Compuestos Bicíclicos con Puentes/síntesis química , Ésteres/química , Éteres Cíclicos/síntesis química , Samario/química , Compuestos Bicíclicos con Puentes/química , Cristalografía por Rayos X , Ciclización , Éteres Cíclicos/química , Modelos Moleculares , Estructura Molecular
11.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 35(4): 466-70, 2015 Apr.
Artículo en Zh | MEDLINE | ID: mdl-26043572

RESUMEN

OBJECTIVE: To explore efficacy enhancing and detoxification roles of Jiedu Quyu Zishen Recipe (JQZR) in treating systemic lupus erythematosus (SLE) by studying its effect on Toll like receptor 9 (TLR9) signal pathway of murine macrophage cells after JQZR stimulated CpG oligodeoxynucletide (CpG ODN). METHODS: Murine macrophage cells in vitro cultured were randomly divided into 4 groups, i.e., the blank serum group, the CpG ODN stimulus group, the CpG ODN + dexamethasone group, the CpG ODN + medicated serum group. Murine macrophage cells were collected after 24-h intervention. The expression of TLR9, myeloid differentiation factor 88 (MyD88), NF-KB, IFN-α mRNA were analyzed by RT-PCR. The expression of TLR9 and NF-κB protein were analyzed by Western blot. Changes of the NF-KB transcriptional activity were assayed by Dual-Luciferase reporter assay system. RESULTS: mRNA expressions of TLR9, MyD88, NF-κB, and IFN-α, protein expressions of TLR9 and NF-κB, and NF-κB transcriptional activities were enhanced, showing statistical difference when compared with those of the blank serum group (P <0. 05, P <0. 01). Compared with the CpG ODN stimulus group, mRNA expressions of MyD88, NF-κB, and IFN-α, the protein expression of NF-κB and the NF-κB transcriptional activities decreased in the CpG ODN + dexamethasone group with statistical difference (P <0. 01). Compared with the CpG ODN stimulus group, mRNA expressions of TLR9, MyD88, NF-κB, and IFN-α, protein expressions of TLR9 and NF-κB, and NF-κB transcriptional activities were decreased in CpG ODN+ medicated serum group with statistical difference (P <0. 01). CONCLUSION: Efficacy enhancing and detoxification roles of JQZR in treatment of SLE might be realized through regulating TLR9 signal pathways.


Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Macrófagos/metabolismo , Receptor Toll-Like 9/metabolismo , Animales , Línea Celular , Humanos , Ratones , Factor 88 de Diferenciación Mieloide , FN-kappa B , ARN Mensajero , Transducción de Señal
12.
Polymers (Basel) ; 16(4)2024 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-38399922

RESUMEN

In the field of high-frequency communications devices, there is an urgent need to develop high-performance copper clad laminates (CCLs) with low dielectric loss (Df) plus good flame retardancy and thermal stability. The hydrocarbon resin styrene-butadiene block copolymer (PSB) was modified with the flame-retardant 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide/polyhedral oligomeric silsesquioxanes (DOPO-POSS) to meet the demands of high-frequency and high-speed applications. The resulting DOPO-POSS-modified PSB was used as the resin matrix along with other additives to fabricate PSB/DOPO-POSS laminates. At a high-frequency of 10 GHz, the laminates containing 20 wt.% of DOPO-POSS and with a thickness of 0.09 mm exhibited a Df of 0.00328, which is much lower compared with the commercial PSB/PX-200 composite (Df: 0.00498) and the PSB without flame retardancy (Df: 0.00453). Afterwards, glass fiber cloth (GF) was used as a reinforcing material to manufacture GF-PSB/DOPO-POSS composite laminates with a thickness of 0.25 mm. The flame retardancy of GF-PSB/DOPO-POSS composite laminate reached vertical burning (UL-94) V-1 grade, and GF-PSB/DOPO-POSS exhibited higher thermal and dynamic mechanical properties than GF-PSB/PX-200. The results of a limited oxygen index (LOI) and self-extinguishing time tests also demonstrated the superior flame-retardant performance of DOPO-POSS compared with PX-200. The investigation indicates that GF-PSB/DOPO-POSS composite laminates have significant potential for use in fabricating a printed circuit board (PCB) for high-frequency and high-speed applications.

13.
Materials (Basel) ; 16(6)2023 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-36984012

RESUMEN

The immobilization of homogeneous catalysts has always been a hot issue in the field of catalysis. In this paper, in an attempt to immobilize the homogeneous [Ni(Me6Tren)X]X (X = I, Br, Cl)-type catalyst with porous organic polymer (POP), the heterogeneous catalyst PBTP-Me6Tren(Ni) (POP-Ni) was designed and constructed by quaternization of the porous bromomethyl benzene polymer (PBTP) with tri[2-(dimethylamino)ethyl]amine (Me6Tren) followed by coordination of the Ni(II) Lewis acidic center. Evaluation of the performance of the POP-Ni catalyst found it was able to catalyze the CO2 cycloaddition with epichlorohydrin in N,N-dimethylformamide (DMF), affording 97.5% yield with 99% selectivity of chloropropylene carbonate under ambient conditions (80 °C, CO2 balloon). The excellent catalytic performance of POP-Ni could be attributed to its porous properties, the intramolecular synergy between Lewis acid Ni(II) and nucleophilic Br anion, and the efficient adsorption of CO2 by the multiamines Me6Tren. In addition, POP-Ni can be conveniently recovered through simple centrifugation, and up to 91.8% yield can be obtained on the sixth run. This research provided a facile approach to multifunctional POP-supported Ni(II) catalysts and may find promising application for sustainable and green synthesis of cyclic carbonates.

14.
Chemosphere ; 336: 139170, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37307931

RESUMEN

Here, the key tasks to be accomplished are selective precious metal recovery from e-wastewater and their conversion into valuable catalysts for peroxymonosulfate (PMS) activation. In this regard, we developed a hybrid material using 3D functional graphene foam and copper para-phenylenedithol (Cu-pPDT) MOF. The prepared hybrid showed a supercilious recovery of 92-95% even up to five cycles for Au(III) and Pd(II), which can be viewed as a reference for both the 2D graphene and the MOFs family. The outstanding performance has been attributed principally to the impact of diverse functionality as well as the unique morphology of 3D graphene foam, which provided a wide range of surface area and additional active sites in the hybrid frameworks. To prepare the surface-loaded metal nanoparticle catalysts, the sorbed samples recovered after precious metal extraction were calcined at 800 °C. The viability of the developed catalysts for the breakdown of 4-nitrophenol (4-NP) via PMS activation was investigated. Electron paramagnetic resonance spectroscopy (EPR) and experiments with radical scavengers suggest that sulfate and hydroxyl radicals are the main reactive species involved in the breakdown of 4-NP. This is because the active graphitic carbon matrix and the exposed precious metal and copper active sites work together in a way that is more effective.


Asunto(s)
Residuos Electrónicos , Grafito , Grafito/química , Cobre , Peróxidos/química , Metales
15.
Chemosphere ; 344: 140332, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37820880

RESUMEN

In this investigation, we successfully synthesized magnetic FeOx nanosphere catalysts with mixed-valence and high operational stability through the pyrolysis of a hybrid material containing polyferrocenlyphosphazene with coordinating heteroatoms (N, P, O). We evaluated the degradation performance of these catalysts using the peroxymonosulfate (PMS) activation process against four different phenolic compounds, namely phenol, 4-nitrophenol, 2,4-dinitrophenol, and 2,4,5-trinitrophenol. Our results demonstrate the significant role of FeOx in the degradation process. The presence of mixed iron species, such as ferric iron, zero-valent iron, and iron oxides, activated PMS to generate radicals. Additionally, the heteroatoms facilitated the anchoring and dispersion of FeOx nanospheres while also breaking the inertness of the carbon structure. Notably, the FeOx-800 catalyst exhibited a maximum degradation activity of 98% for phenol, surpassing its counterparts. Electron paramagnetic resonance and free radical scavenging experiments confirmed that singlet oxygen (1O2) is the principal reactive oxygen species (ROS) that leads to the oxidative breakdown of phenolic compounds. This study introduces new concepts for designing Fenton-like catalysts incorporating heteroatoms into the carbon matrix. Due to their low cost and non-toxicity, these catalysts have recently received a great deal of attention for peroxymonosulfate (PMS) activation and environmental remediation.


Asunto(s)
Nanosferas , Oxígeno Singlete , Peróxidos/química , Hierro/química , Carbono/química , Fenoles , Fenol
16.
Drug Des Devel Ther ; 17: 55-74, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36660249

RESUMEN

Purpose: The network pharmacology analysis, molecular docking and experimental verification were performed to explore the pharmacological mechanisms of Sancao Yuyang Decoction (SCYYD) in the treatment of oral mucositis (OM). Methods: Active ingredients in SCYYD and their potential targets, as well as OM-related targets were screened from public databases. The core targets and signaling pathways of SCYYD against OM were determined by protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The ingredient-target-disease network and target-pathway network were constructed. Subsequently, molecular docking was carried out to predict the binding activity between active ingredients and key targets. Moreover, in vivo experiment was conducted to further verify the core targets predicted by network pharmacology analysis. Results: A total of 119 bioactive ingredients were screened from the corresponding databases. One hundred and eighty-six putative targets were retrieved and bioinformatics analysis was performed to reveal the top 5 potential candidate agents and 10 core targets. GO and KEGG enrichment analysis showed that SCYYD exerted excellent therapeutic effects on OM through several pathways, such as HIF-1 and Ras signaling pathway. Subsequently, molecular docking showed that main ingredients in SCYYD had optimal binding activities to the key protein targets. Moreover, the result of in vivo experiment indicated that SCYYD not only inhibited inflammation response and promoted wound healing of oral mucosa in OM rats, but also reversed high expressions of SRC, HSP90AA1, STAT3, HIF1α, mTOR, TLR4, MMP9, and low expression of ESR1. Conclusion: This study preliminarily uncovered the multiple compounds and multiple targets of SCYYD against OM using network pharmacology, molecular docking and in vivo verification, which provided a new insight of the pharmacological mechanisms of SCYYD in treatment of OM.


Asunto(s)
Medicamentos Herbarios Chinos , Estomatitis , Animales , Ratas , Simulación del Acoplamiento Molecular , Farmacología en Red , Mucosa Bucal , Mapas de Interacción de Proteínas , Medicamentos Herbarios Chinos/farmacología
17.
Int Immunopharmacol ; 119: 110199, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37094544

RESUMEN

Deposition of immune complexes in the glomerulus leads to irreversible renal damage in lupus nephritis (LN), of which podocyte malfunction arises earlier. Fasudil, the only Rho GTPases inhibitor approved in clinical settings, possesses well-established renoprotective actions; yet, no studies addressed the amelioration derived from fasudil in LN. To clarify, we investigated whether fasudil exerted renal remission in lupus-prone mice. In this study, fasudil (20 mg/kg) was intraperitoneally administered to female MRL/lpr mice for 10 weeks. We report that fasudil administration swept antibodies (anti-dsDNA) and attenuated systemic inflammatory response in MRL/lpr mice, accompanied by preserving podocyte ultrastructure and averting immune complex deposition. Mechanistically, it repressed the expression of CaMK4 in glomerulopathy by preserving nephrin and synaptopodin expression. And fasudil further blocked cytoskeletal breakage in the Rho GTPases-dependent action. Further analyses showed that beneficial actions of fasudil on the podocytes required intra-nuclear YAP activation underlying actin dynamics. In addition, in vitro assays revealed that fasudil normalized the motile imbalance by suppressing intracellular calcium enrichment, thereby contributing to the resistance of apoptosis in podocytes. Altogether, our findings suggest that the precise manners of crosstalks between cytoskeletal assembly and YAP activation underlying the upstream CaMK4/Rho GTPases signal in podocytes is a reliable target for podocytopathies treatment, and fasudil might serve as a promising therapeutic agent to compensate for the podocyte injury in LN.


Asunto(s)
Nefritis Lúpica , Podocitos , Femenino , Ratones , Animales , Podocitos/metabolismo , Proteínas de Unión al GTP rho/metabolismo , Ratones Endogámicos MRL lpr , Nefritis Lúpica/tratamiento farmacológico , Citoesqueleto de Actina/metabolismo , Proteína Quinasa Tipo 4 Dependiente de Calcio Calmodulina/metabolismo
18.
Drug Des Devel Ther ; 16: 1947-1961, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35757520

RESUMEN

Purpose: This study was designed to evaluate the pharmacological mechanisms of Aloin against gastric cancer (GC) via network pharmacology analysis combined with experimental verification. Methods: Using network pharmacology methods, the potential targets of Aloin and targets related to GC were screened from public databases. The protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to predict the core targets and pathways of Aloin against GC. The expressions of major targets predicted by network pharmacology in normal stomach tissues and GC tissues and their relationships with overall survival of GC were searched in GEPIA, HPA and DriverDBv3 database. The results of network pharmacology analysis were verified by in vitro experiments. Results: A total of 129 potential targets were retrieved by searching the intersection of Aloin and GC targets. PPI network analysis indicated that 10 targets, including AKT1 and CASP3, were hub genes. GO enrichment analysis involved 93 biological processes, 19 cellular components, and 37 molecular functions. KEGG enrichment analysis indicated that the anti-cancer effect of Aloin was mediated through multiple pathways, such as PI3K-AKT, FoxO and Ras signaling pathway. Among them, the PI3K-AKT signaling pathway, which contained the largest number of enriched genes, may play a greater role in the treatment of GC. The validation of key targets in GEPIA, HPA and DriverDBv3 database showed that the verification results for most core genes were consistent with this study. Then, the results of in vitro experiment indicated that Aloin could inhibit proliferation of NCI-N87 cells and induce cell apoptosis. The results also showed that Aloin could decrease the mRNA and protein expressions of PI3K and AKT, suggesting that Aloin can treat GC by inducing cell apoptosis and regulating the PI3K-AKT signaling pathway. Conclusion: This study identified the potential targets of Aloin against GC using network pharmacology and in vitro verification, which provided a new understanding of the pharmacological mechanisms of Aloin in treatment of GC.


Asunto(s)
Emodina , Neoplasias Gástricas , Emodina/análogos & derivados , Emodina/química , Emodina/farmacología , Humanos , Simulación del Acoplamiento Molecular , Farmacología en Red , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética
19.
Artículo en Inglés | MEDLINE | ID: mdl-35591863

RESUMEN

Jieduquyuziyin prescription (JP) has been used to treat lupus nephritis (LN) and its effectiveness in the treatment of LN has been clinically proven, but the underlying mechanisms have yet to be completely understood. This aim of this study was to clarify the efficacy of JP on the epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells and the molecular mechanisms of JP in MRL/lpr mice. In vivo, we observed the therapeutic actions of JP in MRL/lpr mice as well as its antifibrosis effect and potential mechanism. In vitro, we evaluated the role of JP in EMT and its possible mechanism through the EMT of human renal proximal tubular epithelial cells (HK-2) induced by transforming growth factor-beta 1 (TGF-ß1) and M2c macrophages. HK-2 cells were treated with JP-treated serum, and MRL/lpr mice were treated by JP for 8 weeks. The results showed that JP alleviated disease activity, improved renal function, decreased proteinuria, and improved renal injury and fibrosis in MRL/lpr mice. Furthermore, JP suppressed the activation of the TGF-ß1/Smad2/3 signaling pathway, upregulated the E-cadherin levels, and downregulated the Vimentin and mesenchymal α-smooth muscle actin (α-SMA) levels in the kidney of MRL/lpr mice. JP was further found to prevent the TGF-ß1 and M2c macrophages-induced EMT of HK-2 cells. Collectively, JP could alleviate the disease activity of MRL/lpr mice, improve renal function, and attenuate renal fibrosis, and its underlying mechanisms may be related to the inhibition of EMT and TGF-ß1/Smad2/3 signaling pathway.

20.
Metabolites ; 12(5)2022 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-35629919

RESUMEN

Cardiac involvement, displayed as premature cardiovascular disease (CVD), is one of common clinical symptoms of patients with systemic lupus erythematosus (SLE), contributing to mortality of the disease. The precise underlying pathological mechanism(s) for the cardiac involvement in lupus remains poorly understood. Lipids and their metabolites are directly involved in atherosclerosis development, oxidative stress, and inflammation, which are closely related to the development of CVD. In the study, shotgun lipidomics was exploited to quantitatively analyze cellular lipidomes in the cardiac tissue of MRL/lpr mice at two different time points (i.e., pre-lupus and lupus state) with/without treatment with glucocorticoids (GCs). Urine protein, spleen index, and renal histopathological evaluation of the mice were also performed for assessment of SLE onset and/or outcome. Lipidomics analysis revealed that the deposition of cholesterol and the aberrant metabolism of lipids caused by the increased energy metabolism and the enhanced activation of phospholipases, both of which were originally induced by inflammation, were already present in cardiac tissues from lupus-prone mice even at pre-lupus state. These lipid alterations could further induce inflammation and autoimmune responses, accelerating the process of CVD. In addition, the present study also demonstrated that GCs therapy could not only delay the progression of SLE, but also partially corrected these alterations of lipid species in cardiac tissue due to their anti-inflammatory effect. Thus, the medications with better anti-inflammatory effect might be a useful therapeutic method for premature CVD of SLE.

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