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1.
ACS Appl Mater Interfaces ; 12(2): 2293-2298, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31859469

RESUMO

All-solid-state batteries are expected to be promising next-generation energy storage systems with increased energy density compared to the state-of-the-art Li-ion batteries. Nonetheless, the electrochemical performances of the all-solid-state batteries are currently limited by the high interfacial resistance between active electrode materials and solid-state electrolytes. In particular, elemental interdiffusion and the formation of interlayers with low ionic conductivity are known to restrict the battery performance. Herein, we apply a nondestructive variable-energy hard X-ray photoemission spectroscopy to detect the elemental chemical states at the interface between the cathode and the solid-state electrolyte, in comparison to the widely used angle-resolved (variable-angle) X-ray photoemission spectroscopy/X-ray absorption spectroscopy methods. The accuracy of variable-energy hard X-ray photoemission spectroscopy is also verified with a focused ion beam and high-resolution transmission electron microscopy. We also show the significant suppression of interdiffusion by building an artificial layer via atomic layer deposition at this interface.

2.
Polymers (Basel) ; 11(11)2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31744092

RESUMO

The influence of poly(acrylonitrile-butadiene-styrene) (ABS) as a special ß-nucleating agent on the impact and tensile properties of isotactic polypropylene (iPP) were investigated by dynamic rheological measurements, wide-angle X-ray diffraction (WAXD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and mechanical properties tests. It is found that the ß nucleation efficiency of ABS is closely related to its concentration, dispersibility, and molding method for the iPP/ABS blends. The content of ß-crystal (Kß) rises with the incorporation of ABS and shows a maximum with the introduction of 1% ABS for compression-molded blends and 2% ABS for injection-molded blends, respectively, which is followed by a decrease in Kß. The addition of a small amount of ABS has a significant reinforcing and toughening effect on iPP. Compared with the compression-molded samples, the ABS dispersed phase in injection-molded samples has a smaller particle size and a larger specific surface area, which are favorable for stress transmission and higher ß nucleation efficiency, and therefore, better tensile and impact properties can be expected.

3.
Poult Sci ; 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31539067

RESUMO

The study was conducted to develop a specific, simple, and sensitive method for diagnosis of avian infectious bronchitis virus (IBV). In this experiment, the selected downstream primer was labeled with biotin and the 5' end of RAA probe was labeled with FAM by reverse transcription recombinase-aided amplification (RT-RAA) combined with lateral flow dipstick (LFD). A RT-RAA-LFD assay that could be used for detection of IBV was established after optimization of RT-RAA reaction time, reaction temperature, and primer concentration. This method did not need reverse transcription of IBV template under isothermal condition (37°C), the amplification of target gene fragments could be completed within only 24 min, and the amplification products could be visually observed and determined by LFD within 3 min. The specificity test demonstrated that there was no cross reaction with the nucleic acids of other similar common pathogens. The lowest detectable limit for IBV was 102 copies/µL, and this method was 100 times more sensitive than conventional PCR (104 copies/µL), as verified by sensitivity test. The results showed that RT-RAA-LFD assay with strong specificity and high sensitivity was simple and easy to operate, and could be used for rapid detection of IBV in clinical diagnosis.

4.
ACS Appl Mater Interfaces ; 11(31): 27890-27896, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31298519

RESUMO

Li1.3Al0.3Ti1.7(PO4)3 (LATP) is a popular solid electrolyte used in solid-state lithium batteries due to its high ionic conductivity. Traditionally, the densification of LATP is achieved by a high-temperature sintering process (about 1000 °C). Herein, we report the compaction of LATP by a newly developed cold sintering process and post-annealing. LATP pellets are first densified at 120 °C and then annealed at 650 °C, yielding an ionic conductivity of 8.04 × 10-5 S cm-1 at room temperature and a relative density of 93% with a low activation energy of 0.37 eV. High-resolution transmission electron microscopy of the cold sintered pellets is investigated as well, showing that the particles are interconnected with some nanoprecipitates at the grain boundaries. Such nanocrystalline-enriched grain boundaries are beneficial for lithium-ion transportation, which leads to higher ionic conductivity of the cold sintered sample. This new sintering process can direct new horizons for development of all solid-state batteries due to its simplicity.

5.
Eur J Med Chem ; 179: 623-633, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31279295

RESUMO

Fibrosis is a final pathological feature of many chronic diseases, but few interventions are available that specifically target the pathogenesis of fibrosis. The highlights of common cellular and molecular mechanisms of fibrosis facilitate the discovery of effective antifibrotic drugs. The renin-angiotensin system (RAS) plays a central physiological role in the control of blood pressure and fluid homeostasis. Emerging evidence has revealed that activation of RAS was consistently found in fibrotic tissue. At the same time, as more components of the RAS are described, other pot Potential therapeutic targets emerge, so it seems sensible to revisit the contribution of RAS in anti-fibrotic therapy. So far, angiotensin converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB) are the main commercial available drugs for intervening RAS. However, RAS inhibitors had lots of limitations in long-term application owing to occurring AngII and aldosterone escape. Over the past decades, natural products have aroused growing attention as potential RAS inhibitors due to their high efficacy and low risk of side effects. In this review, we revisit the contribution of RAS and its new members to anti-fibrotic therapy. Ultimately, we summarize and evaluate the use of natural products including isolated compounds, crude extracts and traditional Chinese herbal formulas to regulate RAS. These natural products can retard tissue fibrosis by targeting different RAS components, which provide us new therapeutic strategies to discover anti-fibrotic drugs.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Produtos Biológicos/farmacologia , Fibrose/tratamento farmacológico , Sistema Renina-Angiotensina/efeitos dos fármacos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/química , Inibidores da Enzima Conversora de Angiotensina/química , Produtos Biológicos/química , Relação Dose-Resposta a Droga , Estrutura Molecular , Relação Estrutura-Atividade
6.
Exp Mol Med ; 51(3): 38, 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30918245

RESUMO

Chronic kidney disease (CKD) increases the risk and prevalence of cardiovascular disease (CVD) morbidity and mortality. Recent studies have revealed marked changes in the composition of the microbiome and the metabolome and their potential influence in renal disease and CVD via the accumulation of microbial-derived uremic toxins. However, the effect of unilateral ureteral obstruction (UUO) on the gut microbiome and circulating metabolites is unknown. Male Sprague-Dawley rats were randomized to UUO and sham-operated control groups. Renal histology, colonic microbiota, and plasma metabolites were examined two weeks later. We employed 16S rRNA sequence and untargeted metabolomic analyses to explore the changes in colonic microbiota and plasma metabolites and their relationship with tubulointerstitial fibrosis (TIF). The UUO rats exhibited tubular atrophy and dilatation, interstitial fibrosis and inflammatory cell infiltration in the obstructed kidney. UUO rats showed significant colonic enrichment and depletion of genera. Significant differences were identified in 219 plasma metabolites involved in lipid, amino acid, and bile acid metabolism, which were consistent with gut microbiota-related metabolism. Interestingly, tryptophan and its metabolites kynurenine, 5-hydroxytryptophan and 5-hydroxytryptamine levels, which were linked with TIF, correlated with nine specific genera. Plasma tryptophan level was positively correlated with Clostridium IV, Turicibacter, Pseudomonas and Lactobacillales, and negatively correlated with Oscillibacter, Blautia, and Intestinimonas, which possess the genes encoding tryptophan synthase (K16187), indoleamine 2,3-dioxygenase (K00463) and tryptophan 2,3-dioxygenase (K00453) and their corresponding enzymes (EC:1.13.11.52 and EC:1.13.11.11) that exacerbate TIF. In conclusion, UUO results in profound changes in the gut microbiome and circulating metabolites, events that contribute to the pathogenesis of inflammation and TIF.

7.
J Environ Manage ; 238: 18-24, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30851557

RESUMO

The optimization of energy structures, aimed at saving energy and reducing emissions, is an important precautionary measure against climate change. This study considers different environmental impacts of power systems, and investigates ways to optimize power structures and decrease their potential environmental impact. A multi-objectives optimization model of energy structures was created based on life cycle assessment (LCA). This model covers several environment impacts, rather than only focusing on carbon emissions. LCA was used to calculate the different environmental impacts and provided a new method for normalization. The model was applied to the power industry in China. Three kinds of environmental impacts were considered: material input (MI), global warming potential (GWP), and water deprivation (WD). The five major existing methods of electricity generation in China were considered: thermal power, nuclear power, hydro power, wind power, and solar photovoltaic power. The system boundary included all life cycle stages; specifically, extraction of raw materials and resources, production, energy generation processes, and power transport. The optimization results showed that the total environmental impacts were reduced; MI, GWP, and WD were decreased by 29.53%, 29.67%, and 19.06%, respectively. This method provides new insights into optimization of energy structures by considering multi-environment impacts.


Assuntos
Aquecimento Global , Energia Solar , China , Meio Ambiente , Vento
8.
Free Radic Biol Med ; 134: 484-497, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30716432

RESUMO

Renal ischemia-reperfusion injury (IRI) is a complex syndrome, which causes chronic kidney disease (CKD) after recovery from IRI-mediated acute kidney injury (AKI). There is no single therapy that could effectively prevent the renal injury after ischemia. In this study, the effects of melatonin or poricoic acid A (PAA) and their combination were investigated in protecting against AKI-to-CKD transition in rats and hypoxia/reoxygenation (H/R)-induced injury in cultured renal NRK-52E cells. Melatonin and PAA significantly reduced the magnitude of rise in serum creatinine and urea levels in IRI rats at days 3 and 14. Our results further showed that treatment with melatonin and PAA ameliorated renal fibrosis and podocyte injury by attenuating oxidative stress and inflammation via regulation of nuclear factor-kappa B (NF-κB) and nuclear factor-erythroid-2-related factor 2 (Nrf2) pathways in IRI rats. Melatonin and PAA protected against AKI-to-CKD transition by regulating growth arrest-specific 6 (Gas6)/AxlNFκB/Nrf2 signaling cascade. Melatonin and PAA initiallyupregulated Gas6/Axl signaling to reduce oxidative stress and inflammation in AKI and subsequently downregulated Gas6/Axl signaling to attenuate renal fibrosis and progression to CKD. Melatonin and PAA inhibited expression of extracellular matrix proteins. Poricoic acid A enhances melatonin-mediated inhibition of AKI-to-CKD transition by the regulating Gas6/AxlNFκB/Nrf2 signaling cascade. Notably, our study first identified Axl as a promising therapeutic target for prevention of AKI-to-CKD transition.

9.
Curr Med Chem ; 2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30666906

RESUMO

Rhaponticin is a stilbenoid glucoside compound, can be found in medicinal plant of rhubarb rhizomes. Rhapontigenin (RHAG), the stilbene aglycone metabolite of rhaponticin, has shown various biological activities including anticancer activities to act a potential human cytochrome P450 inhibitor, antihyperlipidemic effect, anti-allergic action, antioxidant and antibacterial activities. Moreover, it was reported to scavenge intravellular reactive oxygen species (ROS), the 1,1-diphenyl-2-picrylliydrazyl (DPPH) radical, and hydrogen peroxide (H2O2). Meanwhile, RHAG exhibited the inhibitory activity for synthesis of DNA, RNA and protein, and also presented the capacity of inducing morphological changes and apoptosis of C. albicans. Here, the structure, pharmacokinetics, pharmacological effects as well as underlying mechanisms of rhaponticin and its metabolite, RHAG, have been extensively reviewed. This review will provide a certain reference value for developing the therapeutic drug of rhaponticin or RHAG.

10.
J Transl Med ; 17(1): 5, 2019 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-30602367

RESUMO

Dysbiosis represents changes in composition and structure of the gut microbiome community (microbiome), which may dictate the physiological phenotype (health or disease). Recent technological advances and efforts in metagenomic and metabolomic analyses have led to a dramatical growth in our understanding of microbiome, but still, the mechanisms underlying gut microbiome-host interactions in healthy or diseased state remain elusive and their elucidation is in infancy. Disruption of the normal gut microbiota may lead to intestinal dysbiosis, intestinal barrier dysfunction, and bacterial translocation. Excessive uremic toxins are produced as a result of gut microbiota alteration, including indoxyl sulphate, p-cresyl sulphate, and trimethylamine-N-oxide, all implicated in the variant processes of kidney diseases development. This review focuses on the pathogenic association between gut microbiota and kidney diseases (the gut-kidney axis), covering CKD, IgA nephropathy, nephrolithiasis, hypertension, acute kidney injury, hemodialysis and peritoneal dialysis in clinic. Targeted interventions including probiotic, prebiotic and symbiotic measures are discussed for their potential of re-establishing symbiosis, and more effective strategies for the treatment of kidney diseases patients are suggested. The novel insights into the dysbiosis of the gut microbiota in kidney diseases are helpful to develop novel therapeutic strategies for preventing or attenuating kidney diseases and complications.

11.
J Cell Physiol ; 234(7): 10602-10614, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30417360

RESUMO

Acute myeloid leukemia (AML) is the most common type of leukemia in adults. AML cells secrete angiogenic factors to remodel vasculature and acquire chemoresistance; however, antiangiogenic drugs are often ineffective in AML treatment. Cancer cell-derived exosomes can induce angiogenesis, but their role in vascular remodeling during AML is unclear. Here, we found that exosomes secreted by AML cells promoted proliferation and migration and tube-forming activity of human umbilical vein endothelial cells (HUVECs), whereas HUVECs conferred chemoresistance to AML cells. AML cell-derived exosomes contained vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) messenger RNA and induced VEGFR expression in HUVECs. Furthermore, they enhanced glycolysis, which correlated with HUVEC proliferation, tube formation, and resistance to apoptosis. Thus, AML cells secrete VEGF/VEGFR-containing exosomes that induce glycolysis in HUVECs leading to vascular remodeling and acquisition of chemoresistance. These findings may contribute to the development of novel therapeutic strategies targeting exosomes in AML.

12.
Nat Commun ; 9(1): 5298, 2018 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-30546010

RESUMO

To balance immunity and tolerance, the endogenous pool of Foxp3+ regulatory T (Treg) cells is tightly controlled, but the underlying mechanisms of this control remain poorly understood. Here we show that the number of Treg cells is negatively regulated by the kinase Lkb1 in dendritic cells (DCs). Conditional knockout of the Lkb1 gene in DCs leads to excessive Treg cell expansion in multiple organs and dampens antigen-specific T cell immunity. Lkb1-deficient DCs are capable of enhancing, compared with wild-type DCs, Treg cell proliferation via cell-cell contact involving the IKK/IKBα-independent activation of the NF-κB/OX40L pathway. Intriguingly, treating wild-type mice with lipopolysaccharide selectively depletes Lkb1 protein in DCs, resulting in Treg cell expansion and suppressed inflammatory injury upon subsequent challenge. Loss of Lkb1 does not obviously upregulate proinflammatory molecules expression on DCs. We thus identify Lkb1 as a regulatory switch in DCs for controlling Treg cell homeostasis, immune response and tolerance.


Assuntos
Proliferação de Células/genética , Células Dendríticas/imunologia , Proteínas Serina-Treonina Quinases/genética , Linfócitos T Reguladores/imunologia , Animais , Apoptose/imunologia , Técnicas de Inativação de Genes , Homeostase/fisiologia , Quinase I-kappa B/metabolismo , Ativação Linfocitária/imunologia , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos SCID , Receptores OX40/metabolismo , Fatores de Necrose Tumoral/metabolismo
13.
ACS Appl Mater Interfaces ; 10(37): 31240-31248, 2018 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-30141900

RESUMO

Solid-state batteries have been considered as one of the most promising next-generation energy storage systems because of their high safety and energy density. Solid-state electrolytes are the key component of the solid-state battery, which exhibit high ionic conductivity, good chemical stability, and wide electrochemical windows. LATP [Li1.3Al0.3Ti1.7 (PO4)3] solid electrolyte has been widely investigated for its high ionic conductivity. Nevertheless, the chemical instability of LATP against Li metal has hindered its application in solid-state batteries. Here, we propose that atomic layer deposition (ALD) coating on LATP surfaces is able to stabilize the LATP/Li interface by reducing the side reactions. In comparison with bare LATP, the Al2O3-coated LATP by ALD exhibits a stable cycling behavior with smaller voltage hysteresis for 600 h, as well as small resistance. More importantly, on the basis of advanced characterizations such as high-resolution transmission electron spectroscope-electron energy loss spectroscopy, the lithium penetration into the LATP bulk and Ti4+ reduction are significantly limited. The results suggest that ALD is very effective in improving solid-state electrolyte/electrode interface stability.

14.
Bioorg Med Chem Lett ; 28(10): 1825-1831, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29657101

RESUMO

A novel series of 5-methyl-2-phenylphenanthridium derivatives were displayed outstanding activity against a panel of antibiotic-sensitive and -resistant bacteria strains compared with their precursor sanguinarine, ciprofloxacin and oxacillin sodium. Compounds 7 l, 7m and 7n were found to display the most effective activity against five sensitive strains (0.06-2 µg/mL) and three resistant strains (0.25-4 µg/mL). The kinetic profiles indicated that compound 7l possessed the strongest bactericidal effect on S. aureus ATCC25923, with the MBC value of 16 µg/mL. The cell morphology and the FtsZ polymerization assays indicated that these compounds inhibited the bacterial proliferation by interfering the function of bacterial FtsZ. The SARs showed that all the 4-methyl-substituted 5-methyl-2-phenylphenanthridium subseries could be further investigated as the FtsZ-targeting antibacterial agents.


Assuntos
Antibacterianos/química , Proteínas de Bactérias/antagonistas & inibidores , Benzofenantridinas/química , Proteínas do Citoesqueleto/antagonistas & inibidores , Isoquinolinas/química , Fenantridinas/química , Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Produtos Biológicos/química , Proteínas do Citoesqueleto/metabolismo , Farmacorresistência Bacteriana/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Simulação de Dinâmica Molecular , Fenantridinas/farmacologia , Estrutura Terciária de Proteína , Relação Estrutura-Atividade
15.
Biochem Biophys Res Commun ; 498(3): 592-596, 2018 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-29522719

RESUMO

Alveolar macrophages (AMs) are pivotal for maintaining the lung homeostasis, but how the development and function of AMs regulated remains largely unknown. In the present study, we demonstrated that the number of AMs was controlled by the Tsc1 protein. Cd11c-specific deletion of Tsc1 caused inefficient transition from pre-AMs to AMs in lung, which led to a great reduction of AM population. Ablation of Tsc1 downregulated the expression of surface marker CD64 and SiglecF on AMs. We further showed that conditional knockout of Tsc1 led to enhanced proliferation and increased reactive oxygen species (ROS) production and phagocytosis in AMs. These results indicated that Tsc1 was a critical regulator of development, proliferation and function in AMs.


Assuntos
Proliferação de Células , Macrófagos Alveolares/citologia , Proteínas Supressoras de Tumor/metabolismo , Animais , Apoptose , Autorrenovação Celular , Células Cultivadas , Deleção de Genes , Macrófagos Alveolares/metabolismo , Camundongos Endogâmicos C57BL , Fagocitose , Espécies Reativas de Oxigênio/metabolismo , Proteína 1 do Complexo Esclerose Tuberosa , Proteínas Supressoras de Tumor/genética
16.
Bioorg Med Chem Lett ; 28(5): 884-891, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29433923

RESUMO

3-Methoxybenzamide (3-MBA) derivatives have been identified as novel class of potent antibacterial agents targeting the bacterial cell division protein FtsZ. As one of isosteres for the amide group, 1,2,3-triazole can mimic the topological and electronic features of the amide, which has gained increasing attention in drug discovery. Based on these considerations, we prepared a series of 1H-1,2,3-triazole-containing 3-MBA analogues via isosteric replacement of the terminal amide with triazole, which had increased antibacterial activity. This study demonstrated the possibility of developing the 1H-1,2,3-triazole group as a terminal amide-mimetic element which was capable of both keeping and modulating amide-related bioactivity. Surprisingly, a different action mode of these new 1H-1,2,3-triazole-containing analogues was observed, which could open new opportunities for the development of antibacterial agents.


Assuntos
Antibacterianos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Triazóis/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/química
17.
Exp Cell Res ; 363(1): 73-83, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29294307

RESUMO

Dendritic cells (DCs) are pivotal to initiating adaptive immune response. Emerging evidence highlights important roles of tuberous sclerosis complex 1 (Tsc1) in DC development and activation. Our previous study also showed that Tsc1 expression in DCs was required to promote T-cell homeostasis and response partially through inhibiting mammalian target of rapamycin complex1 (mTORC1). However, the molecular mechanism of transcriptional regulation by which Tsc1 control DC homeostasis and function remains largely unknown. Here we globally identified the Tsc1-regulated genes by comparing the transcriptional profiling of Tsc1-deficient DCs with wild-type DCs. It showed that Tsc1 specifically regulated the expression of groups of gene sets critically involved in DC survival, proliferation, metabolism and antigen presentation. The impacts of Tsc1 on DC gene expression were partially dependent on inhibition of mTORC1 signal. Our study thus provides a comprehensive molecular basis for understanding how Tsc1 programs the homeostasis and function of DCs through transcriptional regulation.


Assuntos
Células Dendríticas/citologia , Homeostase/fisiologia , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Proteínas Supressoras de Tumor/metabolismo , Animais , Apresentação do Antígeno/imunologia , Células Dendríticas/imunologia , Regulação da Expressão Gênica/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Camundongos Transgênicos , Complexos Multiproteicos/metabolismo , Proteína 1 do Complexo Esclerose Tuberosa , Proteínas Supressoras de Tumor/genética
18.
Front Physiol ; 8: 634, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28936177

RESUMO

Withaferin A (WFA) is one of the most active steroidal lactones with reactive oxygen species (ROS) modulating effects against several types of cancer. ROS regulation involves selective killing. However, the anticancer and selective killing effects of WFA against oral cancer cells remain unclear. We evaluated whether the killing ability of WFA is selective, and we explored its mechanism against oral cancer cells. An MTS tetrazolium cell proliferation assay confirmed that WFA selectively killed two oral cancer cells (Ca9-22 and CAL 27) rather than normal oral cells (HGF-1). WFA also induced apoptosis of Ca9-22 cells, which was measured by flow cytometry for subG1 percentage, annexin V expression, and pan-caspase activity, as well as western blotting for caspases 1, 8, and 9 activations. Flow cytometry analysis shows that WFA-treated Ca9-22 oral cancer cells induced G2/M cell cycle arrest, ROS production, mitochondrial membrane depolarization, and phosphorylated histone H2A.X (γH2AX)-based DNA damage. Moreover, pretreating Ca9-22 cells with N-acetylcysteine (NAC) rescued WFA-induced selective killing, apoptosis, G2/M arrest, oxidative stress, and DNA damage. We conclude that WFA induced oxidative stress-mediated selective killing of oral cancer cells.

19.
Onco Targets Ther ; 10: 3289-3297, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28740404

RESUMO

We previously reported that the soft coral-derived bioactive substance, sinuleptolide, can inhibit the proliferation of oral cancer cells in association with oxidative stress. The functional role of oxidative stress in the cell-killing effect of sinuleptolide on oral cancer cells was not investigated as yet. To address this question, we introduced the reactive oxygen species (ROS) scavenger (N-acetylcysteine [NAC]) in a pretreatment to evaluate the sinuleptolide-induced changes to cell viability, morphology, intracellular ROS, mitochondrial superoxide, apoptosis, and DNA damage of oral cancer cells (Ca9-22). After sinuleptolide treatment, antiproliferation, apoptosis-like morphology, ROS/mitochondrial superoxide generation, annexin V-based apoptosis, and γH2AX-based DNA damage were induced. All these changes were blocked by NAC pretreatment at 4 mM for 1 h. This showed that the cell-killing mechanism of oral cancer cells of sinuleptolide is ROS dependent.

20.
Nat Commun ; 8: 15876, 2017 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-28621313

RESUMO

Regulatory T (Treg) cells are a distinct T-cell lineage characterized by sustained Foxp3 expression and potent suppressor function, but the upstream dominant factors that preserve Treg lineage-specific features are mostly unknown. Here, we show that Lkb1 maintains Treg cell lineage identity by stabilizing Foxp3 expression and enforcing suppressor function. Upon T-cell receptor (TCR) stimulation Lkb1 protein expression is upregulated in Treg cells but not in conventional T cells. Mice with Treg cell-specific deletion of Lkb1 develop a fatal early-onset autoimmune disease, with no Foxp3 expression in most Treg cells. Lkb1 stabilizes Foxp3 expression by preventing STAT4-mediated methylation of the conserved noncoding sequence 2 (CNS2) in the Foxp3 locus. Independent of maintaining Foxp3 expression, Lkb1 programs the expression of a wide spectrum of immunosuppressive genes, through mechanisms involving the augmentation of TGF-ß signalling. These findings identify a critical function of Lkb1 in maintaining Treg cell lineage identity.


Assuntos
Proteínas Serina-Treonina Quinases/metabolismo , Linfócitos T Reguladores/citologia , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Doenças Autoimunes/genética , Linhagem da Célula , Metilação de DNA , Feminino , Fatores de Transcrição Forkhead/genética , Regulação da Expressão Gênica , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , NF-kappa B/metabolismo , Proteínas Serina-Treonina Quinases/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Fator de Transcrição STAT4/genética , Fator de Transcrição STAT4/metabolismo , Linfócitos T Reguladores/fisiologia
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