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1.
Pestic Biochem Physiol ; 200: 105835, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38582597

RESUMO

Octanal was found to be able to reduce green mold incidence in citrus fruit by a defense response mechanism. However, the underlying mechanism remains largely unclear. Herein, the metabolomics, RNA-seq and biochemical analyses were integrated to explore the effect of octanal on disease resistance in harvested citrus fruit. Results showed that octanal fumigation at 40 µL L-1 was effective in controlling citrus green mold. Metabolomics analysis showed that octanal mainly led to the accumulation of some plant hormones including methyl jasmonate, abscisic acid, indole-3-butyric acid, indoleacetic acid (IAA), salicylic acid, and gibberellic acid and many phenylpropanoid metabolites including cinnamyl alcohol, hesperidin, dihydrokaempferol, vanillin, quercetin-3-O-malonylglucoside, curcumin, naringin, chrysin, coniferin, calycosin-7-O-ß-D-glucoside, trans-cinnamaldehyde, and 4',5,7-trihydroxy-3,6-dimethoxyflavone. Particularly, IAA and hesperidin were dramatically accumulated in the peel, which might be the contributors to the resistance response. Additionally, transcriptome analysis showed that octanal greatly activated the biosynthesis and metabolism of aromatic amino acids. This was further verified by the accumulation of some metabolites (shikimic acid, tryptophan, tyrosine, phenylalanine, IAA, total phenolics, flavonoids and lignin), increase in some enzyme activities (phenylalanine ammonia-lyase, tyrosine ammonia-lyase, 4-coumarate CoA ligase, cinnamic acid 4-hydroxylase, polyphenol oxidase, and peroxidase), up-regulation of some genes (tryptophan pyruvate aminotransferase, aldehyde dehydrogenase, shikimate kinase and shikimate dehydrogenase) expressions and molecular docking results. Thus, these results indicate that octanal is an efficient strategy for the control of postharvest green mold by triggering the defense response in citrus fruit.


Assuntos
Aldeídos , Citrus , Hesperidina , Citrus/química , Citrus/genética , Citrus/metabolismo , Aminoácidos Aromáticos/metabolismo , Resistência à Doença , Hesperidina/análise , Hesperidina/metabolismo , Hesperidina/farmacologia , Triptofano/metabolismo , Simulação de Acoplamento Molecular , Frutas
2.
J Am Chem Soc ; 146(11): 7274-7287, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38377953

RESUMO

The utilization of anionic redox chemistry provides an opportunity to further improve the energy density of Li-ion batteries, particularly for Li-rich layered oxides. However, oxygen-based hosts still suffer from unfavorable structural rearrangement, including the oxygen release and transition metal (TM)-ion migration, in association with the tenuous framework rooted in the ionicity of the TM-O bonding. An intrinsic solution, by using a sulfur-based host with strong TM-S covalency, is proposed here to buffer the lattice distortion upon the highly activating sulfur redox process, and it achieves howling success in stabilizing the host frameworks. Experimental results demonstrate the prolonged preservation of the layered sulfur lattice, especially the honeycomb superlattice, during the Li+ extraction/insertion process in contrast to the large structural degeneration in Li-rich oxides. Moreover, the Li-rich sulfide cathodes exhibited a negligible overpotential of 0.08 V and a voltage drop of 0.13 mV/cycle, while maintaining a substantial reversible capacity upon cycling. These superior electrochemical performances can be unambiguously ascribed to the much shorter trajectories of sulfur in comparison to those of oxygen revealed by molecular dynamics simulations at a large scale (∼30 nm) and a long time scale (∼300 ps) via high-dimensional neural network potentials during the delithiation process. Our findings highlight the importance of stabilizing host frameworks and establish general guidance for designing Li-rich cathodes with durable anionic redox chemistry.

3.
Sci Adv ; 9(44): eadj8171, 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37922354

RESUMO

All-solid-state batteries (ASSBs) represent a promising battery strategy to achieve high energy density with great safety. However, inadequate kinetic property and poor interfacial compatibility remain great challenges, which impede their practical application. A prototype of dual-ion conductor of Li+ synchronized with Cu+ unlocks a four-electron redox reaction with high reversibility and fast kinetics. As a result, the constructed ASSB exhibited a high reversible capacity of 603.0 mA·hour g-1 and an excellent cycling retention of 93.2% over 1500 cycles. Moreover, because of the ion highway connecting active materials and catholytes constructed by dual-ion conductor, remarkable temperature tolerance (-60°C) and excellent rate performance (231.6 mA·hour g-1 at 20 mA cm-2) were achieved. The superior electrochemical performance can be ascribed to the migration pathway with small energy barrier and low tortuosity once the Cu+ introduced into Li6PS5Cl. This work creates a unique perspective of ASSBs with dual-ion conducting strategy, thus inspiring a potential developing strategy of state-of-the-art ASSBs.

4.
Front Nutr ; 10: 1287405, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37899831

RESUMO

With the continuous technological innovation in the high-value utilization of rice bran byproducts, rice bran oil retains a higher concentration of beneficial components such as a well-balanced composition of fatty acids and abundant phytosterols. This makes it a highly nutritious and healthy vegetable oil. This review provides an overview of the advancements made in separating, purifying, and processing phytosterols in rice bran oil. The review also introduces techniques for assessing the stability of rice bran oil. Moreover, the review emphasizes the nutritional value of phytosterols found in rice bran oil, highlighting their various health benefits, including their anticancer, anti-inflammatory, anti-allergic, antibacterial, cholesterol-lowering, skin-protective, anti-obesity, anti-diabetic, neuroprotective, gastroprotective, and immune-enhancing effects. Attaining a comprehensive understanding of the research progress made in phytosterols derived from rice bran oil can offer valuable guidance for the efficient utilization of rice bran.

5.
Int Immunopharmacol ; 123: 110768, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37573684

RESUMO

Previous studies have shown that Alisol B 23-acetate (23ABA) had potent liver-protection effects, however, its roles and potential mechanisms in carbon tetrachloride (CCl4)-induced liver fibrosis remain to be determined. The present study aimed to investigate the effects of 23ABA on CCl4-induced liver fibrosis and tried to elucidate the underlying mechanisms by focusing on regulating of farnesoid X receptor (FXR). In vivo study found that 23ABA alleviated the CCl4-induced liver injury, and showed no obvious systemic toxicity on mice. 23ABA inhibited the collagen production, decreased sera levels of hyaluronic acid (HA) and procollagen type III (PC-III), lowered mRNA expression of α-smooth muscle actin (α-SMA), fibronectin, collagen I and collagen III in livers of mice. 23ABA inhibited the mRNA expressions and the sera levels of interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α (TNF-α), as well as decreased the expression of cyclooxygenase 2 (COX-2) in fibrotic livers of mice. Besides, 23ABA decreased levels of reactive oxygen species (ROS) and malondialdehyde (MDA), increased glutathione (GSH) level, enhanced activities of superoxide dismutase (SOD) and glutathione reductase (GR) as well as increased mRNA expression of nuclear factor-E2-related factor 2 (Nrf2), glutamate-cysteine ligase, catalytic subunit (GCLC) and glutamate-cysteine ligase, modifier subunit (GCLM). Further study showed that the anti-liver injury and anti-fibrotic effects of 23ABA were abrogated by FXR antagonist guggulsterone (GS) in vivo. In addition, the inhibition effects of 23ABA on liver inflammation and oxidative stress were also weakened by treatment with GS in CCl4-induced fibrotic mice livers. In conclusion, the protective effects of 23ABA against CCl4-induced liver injury and fibrosis, due to FXR-mediated regulation of liver inflammation and oxidative stress.


Assuntos
Tetracloreto de Carbono , Glutamato-Cisteína Ligase , Animais , Camundongos , Anti-Inflamatórios/farmacologia , Tetracloreto de Carbono/efeitos adversos , Fibrose , Glutamato-Cisteína Ligase/metabolismo , Glutationa/metabolismo , Inflamação , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Estresse Oxidativo , RNA Mensageiro/metabolismo
6.
ACS Cent Sci ; 9(6): 1076-1087, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37396865

RESUMO

Sodium-ion batteries (SIBs) have been deemed to be a promising energy storage technology in terms of cost-effectiveness and sustainability. However, the electrodes often operate at potentials beyond their thermodynamic equilibrium, thus requiring the formation of interphases for kinetic stabilization. The interfaces of the anode such as typical hard carbons and sodium metals are particularly unstable because of its much lower chemical potential than the electrolyte. This creates more severe challenges for both anode and cathode interfaces when building anode-free cells to achieve higher energy densities. Manipulating the desolvation process through the nanoconfining strategy has been emphasized as an effective strategy to stabilize the interface and has attracted widespread attention. This Outlook provides a comprehensive understanding about the nanopore-based solvation structure regulation strategy and its role in building practical SIBs and anode-free batteries. Finally, guidelines for the design of better electrolytes and suggestions for constructing stable interphases are proposed from the perspective of desolvation or predesolvation.

7.
Int J Mol Sci ; 24(4)2023 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-36834940

RESUMO

Although ribosomal RNA processing 15 Homolog (RRP15) has been implicated in the occurrence of various cancers and is considered a potential target for cancer treatment, its significance in colon cancer (CC) is unclear. Thus, this present study aims to determine RRP15 expression and biological function in CC. The results demonstrated a strong expression of RRP15 in CC compared to normal colon specimens, which was correlated with poorer overall survival (OS) and disease-free survival (DFS) of the patients. Among the nine investigated CC cell lines, RRP15 demonstrated the highest and lowest expression in HCT15 and HCT116 cells, respectively. In vitro assays demonstrated that the knockdown of RRP15 inhibited the growth, colony-forming ability and invasive ability of the CC cells whereas its overexpression enhanced the above oncogenic function. Moreover, subcutaneous tumors in nude mice showed that RRP15 knockdown inhibited the CC growth while its overexpression enhanced their growth. Additionally, the knockdown of RRP15 inhibited the epithelial-mesenchymal transition (EMT), whereas overexpression of RRP15 promoted the EMT process in CC. Collectively, inhibition of RRP15 suppressed tumor growth, invasion and EMT of CC, and might be considered a promising therapeutic target for treating CC.


Assuntos
Neoplasias do Colo , Transição Epitelial-Mesenquimal , Proteínas Ribossômicas , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Proteínas Ribossômicas/metabolismo , Processamento Pós-Transcricional do RNA , RNA Ribossômico
8.
Front Pharmacol ; 13: 939317, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120347

RESUMO

Fucosylation is a common glycan terminal modification, which has been reported to be inhibited by 2-fluorofucose (2FF) both in vivo and in vitro. The present study aimed to investigate the effect of 2FF on acetaminophen (APAP)-induced acute liver injury, and further clarified the possible mechanisms. In the present study, inhibition of fucosylation by 2FF relieved APAP-induced acute liver injury in vivo. Pretreatment with 2FF remarkably suppressed APAP-induced oxidative stress and mitochondria damage. 2FF markedly enhanced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and simultaneously promoted the expression of downstream proteins including HO-1 and NQO1. Furthermore, pretreatment with 2FF significantly suppressed the expression of inflammation-associated proteins, such as COX2 and iNOS. The data from lectin blot assay revealed that the alteration of α1,6-fucosylation was involved in APAP-induced acute liver injury. The second part of this study further confirmed that the enhancements to antioxidant capacity of 2FF pretreatment and α1,6-fucose deficiency were related to Nrf2/keap1 and NF-κB signaling pathways in HepG2 cells. Taken together, the current study suggested that 2FF might have a potential therapeutic effect for APAP-induced acute liver injury.

9.
Oxid Med Cell Longev ; 2022: 4061713, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35927991

RESUMO

Wumei Pill (WMP) is a traditional Chinese herbal formulation and widely used to treat digestive system diseases in clinical. S-Adenosylhomocysteine hydrolase (AHCY) can catalyze the hydrolysis of S-adenosylhomocysteine to adenosine and homocysteine in living organisms, and its abnormal expression is linked to the pathogenesis of many diseases including colorectal cancer (CRC). A previous study reported that WMP could prevent CRC in mice; however, the underlying mechanisms especially the roles of AHCY in WMP-induced anti-CRC remain largely unknown. Here, we investigated the regulatory roles and potential mechanisms of AHCY in WMP-induced anti-CRC. WMP notably alleviated the azoxymethane/dextran sulfate sodium- (AOM/DSS-) induced colitis-associated colon cancer (CAC) in mice. Besides, WMP inhibited the inflammation and oxidative stress in AOM/DSS-induced CAC mice. AHCY was high expression in clinical samples of colon cancer compared to the adjacent tissues. WMP inhibited the AHCY expression in AOM/DSS-induced CAC mice. An in vitro study found that AHCY overexpression induced cell proliferation, colony formation, invasion, and tumor angiogenesis, whereas its knockdown impaired its oncogenic function. AHCY overexpression enhanced, while its knockdown weakened the inflammation and oxidative stress in colon cancer cells. Interestingly, WMP potently suppressed the hedgehog (Hh) signaling in AOM/DSS-induced CAC mice. A further study showed that AHCY overexpression activated the Hh signaling while AHCY knockdown inactivated the Hh signaling. Moreover, activation of the Hh signaling reversed the effect of AHCY silencing on inflammation and oxidative stress in vitro. In conclusion, WMP alleviated the AOM/DSS-induced CAC through inhibition of inflammation and oxidative stress by regulating AHCY-mediated hedgehog signaling in mice. These findings uncovered a potential molecular mechanism underlying the anti-CAC effect of WMP and suggested WMP as a promising therapeutic candidate for CRC.


Assuntos
Neoplasias Associadas a Colite , Colite , Neoplasias do Colo , Neoplasias Colorretais , Adenosil-Homocisteinase/metabolismo , Animais , Azoximetano/uso terapêutico , Azoximetano/toxicidade , Colite/induzido quimicamente , Colite/complicações , Colite/tratamento farmacológico , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/tratamento farmacológico , Neoplasias Colorretais/patologia , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Proteínas Hedgehog/metabolismo , Inflamação/complicações , Inflamação/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo
10.
Infect Agent Cancer ; 17(1): 17, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35440002

RESUMO

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) can effectively alleviate liver fibrosis, which is a pathological injury caused by various chronic liver diseases. This study aimed to investigate the antifibrotic effects of BMSCs and elucidate the underlying mechanism by which BMSCs affect liver fibrosis in vitro and in vivo. METHODS: After the rat liver fibrosis model was induced by continuous injection of carbon tetrachloride (CCl4), BMSCs were administered for 4 weeks, and histopathological analysis and liver function tests were performed. T6 hepatic stellate cells (HSC-T6 cells) were stimulated by TGF-ß1, and the activation and proliferation of cells were analyzed by CCK-8 assays, flow cytometry, real-time PCR, western blotting and enzyme-linked immunosorbent assay (ELISA). RESULTS: Our data demonstrated that BMSCs effectively reduced the accumulation of collagen, enhanced liver functionality and ameliorated liver fibrosis in vivo. BMSCs increased the sub-G1 population in HSC-T6 cells. In addition, coculture with BMSCs reduced the expression of α-SMA, collagen I, cyclin-D1, and c-Myc in HSC-T6 cells and activated the phosphorylation of GSK3ß. The GSK3ß inhibitor SB216763 reversed the effect of BMSCs. The Wnt/ß-catenin signalling pathway was involved in BMSC-mediated inhibition of HSC-T6 cell activation. CONCLUSIONS: Our data suggested that BMSCs exerted antifibrotic effects by activating the expression of GSK3ß and inhibiting the Wnt3a/ß-catenin signalling pathway.

11.
Database (Oxford) ; 2021(2021)2021 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-34964846

RESUMO

Pathogenic germline variants in cancer-associated genes are risk factors for cancer predisposition. However, systematic mining and summarizing of cancer pathogenic or likely pathogenic variants has not been performed for people of East Asian descent. This study aimed to investigate publicly available data to identify germline variants in East Asian cancer cohorts and compare them to variants in Caucasian cancer cohorts. Based on the data we retrieved, we built a comprehensive database, named COGVIC (Catalog of Germline Variants in Cancer). A total of 233 variants in the East Asian population were identified. The majority (87%) of genes with cancer-associated variants were not shared between the East Asian and Caucasian cohorts. This included pathogenic variants in BRCA2. Our study summarized the prevalence of germline variants in East Asian cancer cohorts and provides an easy-to-use online tool to explore germline mutations related to cancer susceptibility. DATABASE URL: http://www.cogvic.vip/.


Assuntos
Predisposição Genética para Doença , Neoplasias , Povo Asiático/genética , Células Germinativas , Mutação em Linhagem Germinativa , Humanos , Neoplasias/genética
12.
Front Chem ; 9: 834418, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35186900

RESUMO

The pursuit of electrochemical energy storage has led to a pressing need on materials with high capacities and energy densities; however, further progress is plagued by the restrictive capacity (372 mAh g-1) of conventional graphite materials. Tungsten trioxide (WO3)-based anodes feature high theoretical capacity (693 mAh g-1), suitable potential, and affordable cost, arousing ever-increasing attention and intense efforts. Nonetheless, developing high-performance WO3 electrodes that accommodate lithium ions remains a daunting challenge on account of sluggish kinetics characteristics and large volume strain. Herein, the well-designed hierarchical WO3 agglomerates assembled with straight and parallel aligned nanoribbons are fabricated and evaluated as an anode of lithium-ion batteries (LIBs), which exhibits an ultra-high capacity and excellent rate capability. At a current density of 1,000 mA g-1, a reversible capacity as high as 522.7 mAh g-1 can be maintained after 800 cycles, corresponding to a high capacity retention of ∼80%, demonstrating an exceptional long-durability cyclic performance. Furthermore, the mechanistic studies on the lithium storage processes of WO3 are probed, providing a foundation for further optimizations and rational designs. These results indicate that the well-designed hierarchical WO3 agglomerates display great potential for applications in the field of high-performance LIBs.

13.
Int Immunopharmacol ; 90: 107206, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33246826

RESUMO

Physcion 8-O-ß-glucopyranoside (PSG), an anthraquinone extracted from Rumex japonicus Houtt, has various pharmacological effects, however, the effect of PSG on liver fibrosis and its related mechanism remain to be determined. We here showed that PSG ameliorated liver injury and liver fibrosis, decreased collagen deposition and inhibited inflammation in carbon tetrachloride (CCl4)-induced rats. Consistent with the in vivo results, PSG suppressed the transforming growth factor-ß1 (TGF-ß1)-induced cell viability, liver fibrosis and secretion of inflammatory factors in hepatic stellate cells (HSCs). Interestingly, PSG increased the enzyme activity and promoter activity of sirtuin 3 (SIRT3) in fibrotic liver and activated HSCs. In addition, PSG notably increased the mRNA and protein expression of SIRT3 both in vivo and in vitro. Depletion of SIRT3 either by using 3-TYP (SIRT3 selective inhibitor) or SIRT3 siRNA attenuated the anti-inflammatory effect of PSG in activated HSCs. Further study found that TGF-ß1 increased the nuclear expression of NF-κB p65, but showed no obvious effect on the total NF-κB p65 expression. Compared to the control adenovirus (Ad.mk), overexpression of SIRT3 by infecting adenovirus encoding SIRT3 (Ad.SIRT3) notably decreased the nuclear expression of NF-κB p65 in activated HSCs. Our results demonstrated that PSG attenuated inflammation by regulating SIRT3-mediated NF-κB P65 nuclear expression in liver fibrosis, providing novel molecular insights into the anti-fibrotic effect of PSG.


Assuntos
Anti-Inflamatórios/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Emodina/análogos & derivados , Glucosídeos/farmacologia , Cirrose Hepática Experimental/prevenção & controle , Fígado/efeitos dos fármacos , Sirtuínas/metabolismo , Fator de Transcrição RelA/metabolismo , Animais , Tetracloreto de Carbono , Células Cultivadas , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Colágeno/metabolismo , Emodina/farmacologia , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Fígado/enzimologia , Fígado/patologia , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/enzimologia , Cirrose Hepática Experimental/patologia , Masculino , Ratos Sprague-Dawley , Transdução de Sinais , Sirtuínas/genética
14.
Inflammation ; 44(2): 633-644, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33174138

RESUMO

The regulatory role of toll-like receptor 4 (TLR4) in the inactivate staphylococcus epidermidis (ISE)-induced cornea inflammation is not well investigated. Here, TLR4 silence could decrease inflammatory cytokines in corneal epithelial cells treated with ISE. The mouse corneal epithelial cells were exposed to ISE for 24 h, either alone or with the NF-κB inhibitor, TLR4 lentivirus to bilaterally (knock-down or and overexpression). The expression of TLR4 in mouse corneal epithelial cells was investigated using western blot and qRT-PCR assay. The inflammatory cytokine levels were evaluated by qRT-PCR and ELISA, respectively. The relative impact factors of TLR4-mediated NF-κB signaling detected using western blot assay. Results show the expression levels of TLR4 and some inflammatory cytokines were significantly increased in corneal epithelial cells treated with ISE. TLR4 Silence markedly decreased ISE-induced production of IL12, TNF-α, CCL5, and CCL9 in corneal epithelial cells. Furthermore, the nuclear translocation of NF-κB p65 and myeloid differentiation protein 88 (MyD88) in the cells treated with ISE were further reduced by silencing TLR4. Inhibition of TLR4-mediated NF-κB signaling by using BAY11-7082 also alleviated ISE-induced inflammation. In the rescue experiment, transfected the stable TLR4 silenced corneal epithelial cells with TLR4 overexpression lentivirus, we found that TLR4 overexpression can restore the down-regulation of TLR4 and inflammatory cytokines (IL12, TNF-α, CCL9) caused by TLR4 knocked down. Therefore, ISE-induced cornea inflammation was due to the activation of the TLR4/MyD88/NF-κB signaling pathway, and dramatically stimulated IL12, TNF-α, CCL9 secretion. TLR4 silence presented mitigates damage in corneal epithelial cells treated with ISE.


Assuntos
Células Epiteliais/imunologia , Epitélio Corneano/imunologia , Ceratite/imunologia , Fator 88 de Diferenciação Mieloide/imunologia , NF-kappa B/imunologia , Transdução de Sinais/imunologia , Receptor 4 Toll-Like/imunologia , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Biomarcadores/metabolismo , Western Blotting , Citocinas/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/microbiologia , Epitélio Corneano/efeitos dos fármacos , Epitélio Corneano/metabolismo , Epitélio Corneano/microbiologia , Inativação Gênica , Ceratite/tratamento farmacológico , Ceratite/metabolismo , Ceratite/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Nitrilas/farmacologia , Nitrilas/uso terapêutico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Staphylococcus epidermidis , Sulfonas/farmacologia , Sulfonas/uso terapêutico , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Regulação para Cima
15.
Oxid Med Cell Longev ; 2020: 2452848, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029279

RESUMO

Sirtuin 3 (SIRT3) is a deacetylase involved in the development of many inflammation-related diseases including liver fibrosis. Withaferin A (WFA) is a bioactive constituent derived from the Withania somnifera plant, which has extensive pharmacological activities; however, little is known about the regulatory role of SIRT3 in the WFA-induced antifibrogenic effect. The current study is aimed at investigating the role of SIRT3 in WFA-induced antioxidant effects in liver fibrosis. Our study verified that WFA attenuated platelet-derived growth factor BB- (PDGF-BB-) induced liver fibrosis and promoted PDGF-BB-induced SIRT3 activity and expression in JS1 cells. SIRT3 silencing attenuated the antifibrogenic and antioxidant effects of WFA in activated JS1 cells. Moreover, WFA inhibited carbon tetrachloride- (CCl4-) induced liver injury, collagen deposition, and fibrosis; increased the SIRT3 expression; and suppressed the CCl4-induced oxidative stress in fibrotic livers of C57/BL6 mice. Furthermore, the antifibrogenic and antioxidant effects of WFA could be available in CCl4-induced WT (129S1/SvImJ) mice but were unavailable in CCl4-induced SIRT3 knockout (KO) mice. Our study suggested that WFA inhibited liver fibrosis through the inhibition of oxidative stress in a SIRT3-dependent manner. WFA could be a potential compound for the treatment of liver fibrosis.


Assuntos
Estresse Oxidativo/efeitos dos fármacos , Sirtuína 3/metabolismo , Vitanolídeos/farmacologia , Animais , Antifibrinolíticos/farmacologia , Antifibrinolíticos/uso terapêutico , Becaplermina/farmacologia , Catalase/metabolismo , Sobrevivência Celular , Colágeno/metabolismo , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Cirrose Hepática/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Sirtuína 3/antagonistas & inibidores , Sirtuína 3/genética , Withania/química , Withania/metabolismo , Vitanolídeos/uso terapêutico
16.
Onco Targets Ther ; 13: 9245-9255, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32982311

RESUMO

INTRODUCTION: Owing to its involvement in both the initiation and progression of various cancers, aberrant circular RNA (circRNA) expression has been researched extensively in the recent times. In the present study, we aim to investigate the effect of a novel circRNA has_circ_0025933 (circNELL2) in the progression of esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Sanger sequencing and the detection of circNELL2 level after RNase R or actinomycin D treatment were performed to identify the existence of cirNELL2 in ESCC cells. WST, EDU staining and colony-formation assay were used to assess the proliferation while transwell assay was used to evaluate the migration of ESCC cells. Luciferase assay, RNA pull down and the FISH assay were performed to verify the interaction between circNELL2 and miR-127-5p as well as miR-127-5p and CDC6. Xenograft model was carried out to evaluate the effect of circNELL2 in vivo. RESULTS: circNELL2 was proved to exist in ESCC cells. The up-regulated expression of circNELL2 in the clinical ESCC specimens was also verified. Next, function studies suggested that circNELL2 knockdown inhibited the proliferation of ESCC cells in vitro and in vivo, while circNELL2 overexpression promotes that of ESCC cells. Besides, this study mechanically predicted and verified the target miR of circNELL2, which is miR-127-5p. It was found that miR-127-5p was capable of reversing the effect of circNELL2 on ESCC cells. Moreover, miR-127-5p was also found to target CDC6 to participate in the regulation of cell phenotype. DISCUSSION: circNELL2 promoted the progression of ESCC cells via sponging miR-127-5p, and it has the potential to serve as a novel prognostic and therapeutic target for ESCC.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33414838

RESUMO

Eriodictyol is a flavonoid that belongs to a subclass of flavanones and is widespread in citrus fruits, vegetables, and medicinally important plants. Eriodictyol has been anticipated to explain the method of its activity via multiple cellular signaling cascades. Eriodictyol is an effective natural drug source to maintain higher health standards due to its excellent therapeutic roles in neuroprotection, cardioprotective activity, hepatoprotective activity, antidiabetes and obesity, and skin protection and having highly analgesic, antioxidant, and anti-inflammatory effects, antipyretic and antinociceptive actions, antitumor activity, and much more. This review aims to highlight the modes of action of eriodictyol against various diseases via multiple cellular signaling pathways.

18.
J Cell Mol Med ; 24(1): 941-953, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31742890

RESUMO

Celastrol, a pentacyclic tritepene extracted from Tripterygium Wilfordi plant, showing potent liver protection effects on several liver-related diseases. However, the anti-inflammatory potential of celastrol in liver fibrosis and the detailed mechanisms remain uncovered. This study was to investigate the anti-inflammatory effect of celastrol in liver fibrosis and to further reveal mechanisms of celastrol-induced anti-inflammatory effects with a focus on AMPK-SIRT3 signalling. Celastrol showed potent ameliorative effects on liver fibrosis both in activated hepatic stellate cells (HSCs) and in fibrotic liver. Celastrol remarkably suppressed inflammation in vivo and inhibited the secretion of inflammatory factors in vitro. Interestingly, celastrol increased SIRT3 promoter activity and SIRT3 expression both in fibrotic liver and in activated HSCs. Furthermore, SIRT3 silencing evidently ameliorated the anti-inflammatory potential of celastrol. Besides, we found that celastrol could increase the AMPK phosphorylation. Further investigation showed that SIRT3 siRNA decreased SIRT3 expression but had no obvious effect on phosphorylation of AMPK. In addition, inhibition of AMPK by employing compound C (an AMPK inhibitor) or AMPK1α siRNA significantly suppressed SIRT3 expression, suggesting that AMPK was an up-stream protein of SIRT3 in liver fibrosis. We further found that depletion of AMPK significantly attenuated the inhibitory effect of celastrol on inflammation. Collectively, celastrol attenuated liver fibrosis mainly through inhibition of inflammation by activating AMPK-SIRT3 signalling, which makes celastrol be a potential candidate compound in treating or protecting against liver fibrosis.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Anti-Inflamatórios/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Triterpenos Pentacíclicos/farmacologia , Sirtuínas/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Animais , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/imunologia , Células Estreladas do Fígado/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Cirrose Hepática/imunologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Sirtuínas/genética
19.
Atherosclerosis ; 288: 124-136, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31362179

RESUMO

BACKGROUND AND AIMS: The physiological role of Rho-specific guanine nucleotide dissociation inhibitor (RhoGDI) in vascular remodeling remains unknown. We investigated the function of RhoGDI in angiotensin II (Ang II)-induced vascular remodeling in cultured human aortic vascular smooth muscle cells (HA-VSMCs) and in an Ang II-infusion vascular remodeling mouse model. METHODS: For in vitro assays of HA-VSMCs, proliferation was assessed by BrdU and EdU assays and immunofluorescence analysis of ki-67 expression. RhoGDI1 and RhoGDI2 function and expression were assessed by RNAi, Western blotting and real-time RT-PCR. RhoGDI ubiquitination and SUMOylation levels were evaluated by co-immunoprecipitation and Western blotting. The functions of proteosomal-mediated degradation, ubiquitination, SUMOylation and Ang II receptors were assessed using specific inhibitors. To evaluate the in vivo effects of Ang II and RhoGDI, H & E staining, Masson's trichrome staining, and immunostaining were employed. RESULTS: Ang II treatment of HA-VSMCs for 6 or 48 h promoted RhoGDI1 and RhoGDI2 protein degradation and reduced cell proliferation, which was reversed by proteosome inhibition. In contrast, treatment with Ang II for 12 or 24 h induced dose-dependent cell proliferation without affecting RhoGDI expression. RNA interference of either RhoGDI1 or RhoGDI2 blocked proliferation induced by 12 or 24 h treatment of Ang II. Moreover, Ang II-dependent degradation at 6 and 48 h correlated with RhoGDI ubiquitination and inversely correlated with RhoGDI SUMOylation and cell proliferation. Treatment with specific inhibitors suggests that ubiquitin and SUMO competitively bind to RhoGDI1 and RhoGDI2 to reciprocally regulate RhoGDI stability and HA-VSMC proliferation. Furthermore, inhibition of the Ang II receptor 1 (AT1 receptor), but not the Ang II receptor 2, blocked Ang II-dependent RhoGDI stabilization and proliferation at 12 and 24 h. In mice, Ang II infusion increased the intima-media thickness, collagen and myofiber production and VSMC proliferation, and these effects were shown to be dependent on RhoGDI1, RhoGDI2 and AT1 receptor. Ang II infusion exerted no significant effect on RhoGDI1 and RhoGDI2 protein levels, which were decreased after AT1 receptor inhibition. CONCLUSIONS: Together, the results of this study reveal a novel mechanism by which Ang II regulates RhoGDI stability by SUMOylation and ubiquitination via AT1 receptor activation and thus affects VSMC proliferation and vascular remodeling.


Assuntos
Angiotensina II/farmacologia , Proliferação de Células/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Receptor Tipo 1 de Angiotensina/agonistas , Ubiquitinação , Remodelação Vascular/efeitos dos fármacos , Inibidor alfa de Dissociação do Nucleotídeo Guanina rho/metabolismo , Inibidor beta de Dissociação do Nucleotídeo Guanina rho/metabolismo , Animais , Células Cultivadas , Humanos , Masculino , Camundongos Endogâmicos C57BL , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Neointima , Complexo de Endopeptidases do Proteassoma/metabolismo , Estabilidade Proteica , Proteólise , Receptor Tipo 1 de Angiotensina/metabolismo , Transdução de Sinais , Sumoilação , Inibidor alfa de Dissociação do Nucleotídeo Guanina rho/genética , Inibidor beta de Dissociação do Nucleotídeo Guanina rho/genética
20.
Gen Physiol Biophys ; 38(4): 271-280, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31219429

RESUMO

The aim of this study was to investigate the effects of the Rho GDP dissociation inhibitor (RhoGDI) on TGFß1-mediated vascular adventitia myofibroblast transdifferentiation and on the inhibition of ROCK inhibitors. Myofibroblast transdifferentiation and vascular remodeling model were induced by TGFß1 in vitro and by balloon injury in vivo. H&E (Hematoxylin & Eosin) and PSR (Picrosirius Red) staining were used to observe vascular morphology while immunofluorescence, immunohistochemistry, and Western blotting were used to measure protein expression. Fasudil treatment reduced the expression of TGFß1, RhoGDI1, and RhoGDI2 in addition to vascular remodeling in the rat balloon injury model. TGFß1 induced the expression of α-SMA, TGFßRI, phospho-TGFßRI, RhoGDI1, RhoGDI2, and collagen secretion in human aortic adventitial fibroblasts (HAAFs). These effects were diminished after treatment with Y27632. Suppressing both RhoGDI1 and RhoGDI2 expression also blocked TGFß1-induced α-SMA expression and collagen secretion in HAAFs. Moreover, TGFßR inhibition blocked TGFß1-mediated collagen secretion and the expression of α-SMA, RhoGDI1, and RhoGDI2. These data suggested that ROCK inhibitors alleviate myofibroblast transdifferentiation and vascular remodeling by decreasing TGFß1-mediated expression of RhoGDI.


Assuntos
Transdiferenciação Celular/efeitos dos fármacos , Miofibroblastos/citologia , Miofibroblastos/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Remodelação Vascular/efeitos dos fármacos , Quinases Associadas a rho/antagonistas & inibidores , Inibidores da Dissociação do Nucleotídeo Guanina rho-Específico/biossíntese , Animais , Humanos , Ratos
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