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Industrial urea synthesis production uses NH3 from the Haber-Bosch method, followed by the reaction of NH3 with CO2, which is an energy-consuming technique. More thorough evaluations of the electrocatalytic C-N coupling reaction are needed for the urea synthesis development process, catalyst design, and the underlying reaction mechanisms. However, challenges of adsorption and activation of reactant and suppression of side reactions still hinder its development, making the systematic review necessary. This review meticulously outlines the progress in electrochemical urea synthesis by utilizing different nitrogen (NO3 -, N2, NO2 -, and N2O) and carbon (CO2 and CO) sources. Additionally, it delves into advanced methods in materials design, such as doping, facet engineering, alloying, and vacancy introduction. Furthermore, the existing classes of urea synthesis catalysts are clearly defined, which include 2D nanomaterials, materials with Mott-Schottky structure, materials with artificially frustrated Lewis pairs, single-atom catalysts (SACs), and heteronuclear dual-atom catalysts (HDACs). A comprehensive analysis of the benefits, drawbacks, and latest developments in modern urea detection techniques is discussed. It is aspired that this review will serve as a valuable reference for subsequent designs of highly efficient electrocatalysts and the development of strategies to enhance the performance of electrochemical urea synthesis.
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Aqueous zinc-ion batteries (ZIBs) stand out as a promising next-generation electrochemical energy storage technology, offering notable advantages such as high specific capacity, enhanced safety, and cost-effectiveness. However, the application of aqueous electrolytes introduces challenges: Zn dendrite formation and parasitic reactions at the anode, as well as dissolution, electrostatic interaction, and by-product formation at the cathode. In addressing these electrode-centric problems, additive engineering has emerged as an effective strategy. This review delves into the latest advancements in electrolyte additives for ZIBs, emphasizing their role in resolving the existing issues. Key focus areas include improving morphology and reducing side reactions during battery cycling using synergistic effects of modulating anode interface regulation, zinc facet control, and restructuring of hydrogen bonds and solvation sheaths. Special attention is given to the efficacy of amino acids and zwitterions due to their multifunction to improve the cycling performance of batteries concerning cycle stability and lifespan. Additionally, the recent additive advancements are studied for low-temperature and extreme weather applications meticulously. This review concludes with a holistic look at the future of additive engineering, underscoring its critical role in advancing ZIB performance amidst the complexities and challenges of electrolyte additives.
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BACKGROUND: Meningioma, the most prevalent intracranial tumor, possesses a significant propensity for malignant transformation. Circular RNAs (circ-RNAs), a class of non-coding RNAs, have emerged as crucial players in tumorigenesis. This study explores the functional relevance of hsa_circ_0004872, a specific circ-RNA, in the context of meningioma. METHODS: Molecular structure and stability of hsa_circ_0004872 were elucidated through PCR identification. Meningioma cell proliferation and apoptosis were assessed using the CCK-8 assay and flow cytometry, respectively. Gene and protein expression were analyzed via qRT-PCR and western blot. Molecular interactions were confirmed through dual-luciferase reporter gene and RIP assays. RESULTS: Hsa_circ_0004872, derived from exons 2 to 4 of the host gene MAPK1, demonstrated enhanced stability compared to its host MAPK1. Clinical data described that hsa_circ_0004872 was reduced in meningioma tissues and cell lines, and negatively correlated to poor survival rate of meningioma patients. Overexpression of hsa_circ_0004872 exhibited inhibitory effects on cell proliferation and promotion of apoptosis in vitro. Subsequent investigations unveiled a direct interaction between hsa_circ_0004872 and miR-190a-3p, leading to the activation of the PI3K/AKT signaling pathway through targeting PTEN. Notably, miR-190a-3p silence accelerated the apoptosis and proliferation inhibition of meningioma cells by inactivating PTEN/PI3K/AKT signaling, while miR-190a-3p overexpression showed an opposite effect, which greatly reversed the anti-tumor effects of hsa_circ_0004872 overexpression. CONCLUSION: In summary, our findings highlighted the intricate role of hsa_circ_0004872 in meningioma, shedding light on the regulatory mechanisms involving circ-RNAs in tumor progression. This positions hsa_circ_0004872 as a potential key regulatory factor in meningioma with implications for future therapeutic interventions.
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Neoplasias Meníngeas , Meningioma , MicroRNAs , Humanos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/genética , Transformação Celular Neoplásica , Regulação Neoplásica da Expressão Gênica , Neoplasias Meníngeas/genética , Meningioma/genética , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , PTEN Fosfo-Hidrolase/genética , Transdução de Sinais/genéticaRESUMO
Designing electrocatalysts with strong electronic metal-support interaction can effectively regulate the electronic properties of metal active centers, therefore maximizing the catalytic performance. As a proof of concept, heteroatoms doped carbon with CoPt alloy and isolated Co single atoms (CoPtCoSA@NSC) are synthesized using CoPt bimetallic metal-organic framework as the precursor in this work. The existence of CoSA on the carbon substrate leads to more electron transfer between CoPt and the support, and appropriate upward shift of the d band center of the catalysts, which can effectively reduce the reaction barrier of rate determine step and boost the catalytic performance of CoPt alloy. The enhanced catalytic activity and stability of CoPtCoSA@NSC are demonstrated experimentally. Remarkably, the overpotential for hydrogen evolution reaction is only 23 mV at 10 mA cm-2 and the half-wave potential for oxygen reduction reaction is 0.90 V, both exceeding the commercial Pt/C benchmark. In addition, CoPtCoSA@NSC also exhibits great potential as a cathode electrocatalyst for Zn-air battery, in terms of large open circuit potential of 1.53 V, high power density of 184 mW cm-2 , as well as superior cycling stability. This work provides a novel strategy for regulating the electronic structure and catalytic performance of alloy based electrocatalysts.
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The efficacy of lithium-sulfur (Li-S) batteries crucially hinges on the sulfur immobilization process, representing a pivotal avenue for bolstering their operational efficiency and durability. This dissertation primarily tackles the formidable challenge posed by the high solubility of polysulfides in electrolyte solutions. Quantum chemical computations were leveraged to scrutinize the interactions of MXene materials, graphene (Gr) oxide, and ionic liquids with polysulfides, yielding pivotal binding energy metrics. Comparative assessments were conducted with the objective of pinpointing MXene materials, with a specific focus on d-Ti3C2 materials, evincing augmented binding energies with polysulfides and ionic liquids demonstrating diminished binding energies. Moreover, a diverse array of Gr oxide materials was evaluated for their adsorption capabilities. Scrutiny of the computational outcomes unveiled an augmentation in the solubility of selectively screened d-Ti3C2 MXene and ionic liquids-vis à vis one or more of the five polysulfides. Therefore, the analysis encompasses an in-depth comparative assessment of the stability of polysulfide adsorption by d-Ti3C2 MXene materials, Gr oxide materials, and ionic liquids across diverse ranges.
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The insufficient contact between two phases in the heterostructure weakens the coupling interaction effect, which makes it difficult to effectively improve the electrochemical performance. Herein, a Co-carbonate hydroxide@ Ni-metal organic frameworks (Co-CH@Ni-MOFs) composite with super uniform core-shell heterostructure is fabricated by adopting 1D Co-CH nanowires as structuredirecting agents to induce the coating of Ni-MOFs. Both experimental and theoretical calculation results demonstrate that the heterostructure plays a vital role in the high performance of the as-prepared materials. On the one hand, the construction of super uniform core-shell heterostructure can create a large number of interfacial active sites and take advantages of the electrochemical characteristics of each component. On the other hand, the heterostructure can increase the adsorption energy of OH- ions and promote the electrochemical activity for improving the reversible redox reaction kinetics. Based on the aforementioned advantages, the as-fabricated Co-CH@Ni-MOFs electrode exhibits a high specific capacity of 173.1 mAh g-1 (1246 F g-1 ) at 1 A g-1 , an ultrahigh rate capability of 70.3% at 150 A g-1 and excellent cycling stability with 90.1% capacity retention after 10 000 cycles at 10 A g-1 . This study may offer a versatile design for fabricating a MOFs-based heterostructure as energy storage electrodes.
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Controlling the crystallographic orientations of 2D perovskite is regarded as an effective way to improve the efficiency of PSCs based on 2D perovskite. In this paper, five different assistant solvents were selected to unveil the effect of solvents on crystallization and morphology of 2D perovskite in a solvent-assisted method. Results demonstrated that the effect of Lewis basicity on the crystallization process was the most important factor for preparing 2D perovskite. The stability of the intermediate, reacted between the solvent and the Pb2+, determined the quality of 2D film. The stronger the Lewis basicity was, the more obvious the accurate control effect on the top-down crystallization process of 2D perovskite would be. This could enhance the crystallographic orientation of 2D perovskite. The effect of Lewis basicity played a more important role than other properties of the solvent, such as boiling point and polarity.
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BACKGROUND: Recent evidences have shown that circular RNAs (circRNAs) are frequently dysregulated and play paramount roles in various cancers. circRNAs are abundant in central nervous system (CNS); however, few studies describe the clinical significance and role of circRNAs in gliomas, which is the most common and aggressive primary malignant tumor in the CNS. METHODS: A bioinformatics analysis was performed to profile and screen the dyregulated circRNAs during early neural development. Quantitative real-time PCR was used to detect the expression of circ-MAPK4 and target miRNAs. Glioma cells were transfected with circ-MAPK4 siRNAs, then cell proliferation, apoptosis, transwell assays, as well as tumorigenesis and TUNEL assays, were performed to examine effect of circ-MAPK4 in vitro and vivo. Biotinylated-circ-MAPK4 probe based pull-down assay was conducted to confirm the relationship between circ-MAPK4 and miR-125-3p. RESULTS: In this study, we identified a circRNA, circ-MAPK4 (has_circ_0047688), which was downregulated during early neural differentiation. In gliomas, circ-MAPK4 acted as an oncogene, was inversely upregulated and linked to clinical pathological stage of gliomas (P < 0.05). Next, we verified that circ-MAPK4 promoted the survival and inhibited the apoptosis of glioma cells in vitro and in vivo. Furthermore, we proved that circ-MAPK4 was involved in regulating p38/MAPK pathway, which affected glioma proliferation and apoptosis. Finally, miR-125a-3p, a miRNA exhibited tumor-suppressive function through impairing p38/MAPK pathway, which was increased by inhibiting circ-MAPK4 and could be pulled down by circ-MAPK4. Inhibition of miR-125a-3p could partly rescue the increased phosphorylation levels of p38/MAPK and the elevated amount of apoptosis inducing by knockdown of circ-MAPK4. CONCLUSIONS: Our findings suggest that circ-MAPK4 is a critical player in glioma cell survival and apoptosis via p38/MAPK signaling pathway through modulation of miR-125a-3p, which can serve as a new therapeutic target for treatment of gliomas.
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Biomarcadores Tumorais/genética , Glioma/patologia , MicroRNAs/genética , RNA Helicases/genética , RNA Circular/genética , Adulto , Idoso , Animais , Apoptose , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Glioma/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Fosforilação , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto Jovem , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Carbon-based, non-noble metal catalysts for the oxygen reduction reaction (ORR) are crucial for the large-scale application of metal-air batteries and fuel cells. Density functional theory calculations were performed to explore the potential of atomically dispersed MN4/C (M = Fe or Mn) as an ORR catalyst in an acidic electrolyte and the ORR mechanism on MN4/C was systematically studied. The results indicated MN4 as the active site of MN4/C and a four-electron OOH transformation pathway as the preferred ORR mechanism on the MN4/C surface. The Gibbs free energy diagram showed that the rate-determining step of the FeN4/C and MnN4/C catalysts is the formation of the second H2O molecule and OOH*, respectively. FeN4/C exhibited higher thermodynamic limiting potential (0.79 V) and, thus, higher ORR activity than MnN4/C (0.52 V) in an acidic environment; its excellent catalytic performance is due to the nice electron structure and adsorption properties of the FeN4 site. Therefore, this work demonstrates that atomically dispersed MN4/C is a promising catalyst for the ORR.
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Osteoarthritis (OA) is characterized by progressive destruction of articular cartilage, resulting in significant disability. Chondrocytes present in various types of cartilage and are responsible for the growth and maintenance of the tissue. Over-proliferation of human chondrocytes may contributes to OA pathological process. Previously, we revealed that miR-127-5p could inhibit the proliferation of human chondrocytes through osteopontin (OPN). In the present study, we used online tools to figure out several candidates lncRNAs which were potentially correlated with miR-127-5p. Through assessing the expression levels of the candidates lncRNAs, metastasis associated lung adenocarcinoma transcript 1 (MALAT1) was chosen as a further research subject. MALAT1 knockdown significantly repressed human OA chondrocyte proliferation, as well as the protein levels of OPN, p-PI3K, and p-Akt in OA chondrocytes. As verified by luciferase assays, MALAT1 directly bound to miR-127-5p to inhibit miR-127-5p expression. Then we achieved miR-127-5p inhibition through miR-127-5p inhibitor transfection; the miR-127-5p inhibition could promote chondrocyte proliferation, as well as the protein levels of OPN, p-PI3K, and p-Akt; in addition, the MALAT1 knockdown partially reversed the promotive effect of miR-127-5p inhibition on chondrocyte proliferation, OPN and PI3K/Akt signaling-related protein levels. Taken together, MALAT1 could directly bind to miR-127-5p to inhibit its expression, so as to rescue OPN expression and promote chondrocyte proliferation through PI3K/Akt pathway. Targeting MALAT1 so as to rescue miR-127-5p expression in OA might help to inhibit chondrocyte proliferation through miR-127-5p-mediated OPN regulation and downstream PI3K/Akt pathway. J. Cell. Biochem. 119: 431-439, 2018. © 2017 Wiley Periodicals, Inc.
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Proliferação de Células , Condrócitos/metabolismo , MicroRNAs/metabolismo , Osteopontina/biossíntese , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Células Cultivadas , Condrócitos/citologia , HumanosRESUMO
In central nervous system, glioma is the most common primary brain tumour. The diffuse migration and rapid proliferation are main obstacles for successful treatment. Gartanin, a natural xanthone of mangosteen, suppressed proliferation, migration and colony formation in a time- and concentration-dependent manner in T98G glioma cells but not in mouse normal neuronal HT22 cells. Gartanin, at low micromole, led to cell cycle arrest in G1 phase accompanied by inhibited expression level of G1 cell cycle regulatory proteins cyclin D1, while increased expression level of cyclin-dependent kinase inhibitor p27Kip1. In addition, the secretion and activity of matrix metalloproteinases 2/9 (MMP-2/-9) were significantly suppressed in T98G cells treated with gartanin, and it might result from modulating mitogen-activated protein kinases (MAPK) signalling pathway in T98G glioma cells. Moreover, gartanin significantly induced autophagy in T98G cells and increased GFP-LC3 punctate fluorescence accompanied by the increased expression level of Beclin 1 and LC3-II, while suppressed expression level of p62. Gartanin treatment resulted in obvious inhibition of PI3K/Akt/mTOR signalling pathway, which is important in modulating autophagy. Notably, gartanin-mediated anti-viability was significantly abrogated by autophagy inhibitors including 3-methyladenine (3-MA) and chloroquine (CQ). These results indicate that anti-proliferation effect of gartanin in T98G cells is most likely via cell cycle arrest modulated by autophagy, which is regulated by PI3K/Akt/mTOR signalling pathway, while anti-migration effect is most likely via suppression of MMP-2/-9 activity which is involved in MAPK signalling pathway.
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Autofagia/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Glioma/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Xantonas/farmacologia , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fase G1/efeitos dos fármacos , Glioma/metabolismo , Humanos , Camundongos , Transdução de Sinais/efeitos dos fármacosRESUMO
CONTEXT: Osteoarthritis (OA) is a common chronic degenerative joint disease resulting in physical disability and reduced quality of life. Different biochemical signaling pathways are involved in the progression of OA, including the c-Jun NH2-terminal kinase (JNK) signal transduction pathway. OBJECTIVE: In this study, we have reviewed the recent updates on the association of JNK pathway with OA. METHODS: In this review, we have explored the databases like PubMed, Google Scholar, Medline, Scopus, etc., and collected the most relevant papers of JNK signaling pathway involved in the pathogenesis and therapeutics of OA Results: JNK has been shown by scientific studies to be activated (phosphorylated) in OA that can play a key role in the cartilage destruction. Activation of JNK causes the phosphorylation of c-Jun that causes decreased proteoglycan synthesis and enhanced production of matrix metalloproteinase 13 (MMP-13). Overproduction of MMP-13 by chondrocytes plays a central role in cartilage degeneration in OA. Thus, targeting JNK pathway might be a promising therapeutic application for the prevention and treatment of OA. A number of JNK-inhibitors have been used in vitro and in vivo studies; however, not yet been translated into human use. CONCLUSIONS: This review study indicates that JNK pathway plays an important role in development and progression of OA, and targeting the JNK pathway might be a potential approach for the treatment of OA in future.
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Proteínas Quinases JNK Ativadas por Mitógeno/genética , Terapia de Alvo Molecular , Osteoartrite/genética , Osteoartrite/terapia , Regulação da Expressão Gênica/genética , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Metaloproteinase 13 da Matriz/genética , Redes e Vias Metabólicas/genética , Osteoartrite/patologia , Fosforilação/genéticaRESUMO
Survival of patients with glioblastoma (GBM) remains poor, and novel treatment methods are urgently needed. In this study, we tested the effects of a combination of fasudil, a ROCK inhibitor, and clioquinol, an 8-hydroxyquinoline derivative with antimicrobial properties, on human GBM U87 cells. Combination treatment synergistically inhibited the viability of glioma cells but not mouse normal neuron HT22 cells and significantly induced mitochondria-mediated apoptosis. Moreover, the combination was also found to trigger macro-autophagy (henceforth referred to as autophagy) by increasing the expression levels of several proteins involved in the induction of autophagy. Further studies showed that 3-methyladenine (3-MA) or chloroquine (CQ), two autophagy inhibitors, abrogated the cytotoxic effects of the combination treatment as well as the autophagy. Overall, we demonstrated that fasudil and clioquinol show synergistic anti-cancer effects, providing evidence for the further development of combination therapy for GBM.
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1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Clioquinol/farmacologia , Sinergismo Farmacológico , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Animais , Western Blotting , Neoplasias Encefálicas/metabolismo , Proliferação de Células/efeitos dos fármacos , Quimioterapia Combinada , Citometria de Fluxo , Glioblastoma , Humanos , Camundongos , Mitocôndrias/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Células Tumorais CultivadasRESUMO
OBJECTIVE Ventriculoperitoneal (VP) shunt treatment is the main treatment method for hydrocephalus. The traditional operative approach for peritoneal catheter insertion is mini-laparotomy. In recent years, laparoscopy-assisted insertion has become increasingly popular. It seems likely that use of an endoscope could lower the incidence of shunt malfunction. However, there is no consensus about the benefits of laparoscopy-assisted peritoneal catheter insertion. METHODS A systematic search was performed using the PubMed, Embase, ScienceDirect, and Cochrane Library databases. A manual search for reference lists was conducted. The protocol was prepared according to the interventional systematic reviews of the Cochrane Handbook, and the article was written on the basis of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. RESULTS Eleven observational trials and 2 randomized controlled trials were included. Seven operation-related outcome measures were analyzed, and 3 of these showed no difference between operative techniques. The results of the meta-analysis are as follows: in the laparoscopy group, the rate of distal shunt failure was lower (OR 0.41, 95% CI 0.25-0.67; p = 0.0003), the absolute effect is 7.11% for distal shunt failure, the number needed to treat is 14 (95% CI 8-23), operative time was shorter (mean difference [MD], -12.84; 95% CI -20.68 to -5.00; p = 0.001), and blood loss was less (MD -9.93, 95% CI -17.56 to -2.31; p = 0.01). In addition, a borderline statistically significant difference tending to laparoscopic technique was observed in terms of hospital stay (MD -1.77, 95% CI -3.67 to 0.13; p = 0.07). CONCLUSIONS To some extent, a laparoscopic insertion technique could yield a better prognosis, mainly because it is associated with a lower distal failure rate and shorter operative time, which would be clinically relevant.
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Hidrocefalia/cirurgia , Laparoscopia/tendências , Laparotomia/tendências , Derivação Ventriculoperitoneal/tendências , Humanos , Hidrocefalia/diagnóstico , Laparoscopia/efeitos adversos , Laparotomia/efeitos adversos , Tempo de Internação/tendências , Estudos Observacionais como Assunto/métodos , Cavidade Peritoneal/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Derivação Ventriculoperitoneal/efeitos adversosRESUMO
BACKGROUND: Neurite outgrowth is one of the important therapeutic strategies for neuronal plasticity and regeneration in neural disorders. Fasudil is a clinical medication that is used to treat subarachnoid haemorrhage (SAH) and that is beneficial for many animal models of central nervous system (CNS) diseases. In this study, we hypothesised that fasudil administration would promote neurite outgrowth in neural stem cells (NSCs). METHODS: Changes in cell morphology were imaged under a light microscope, and neurite-bearing cells were counted. Cell viability and the necrosis rate were determined by MTT and LDH assays, respectively. Additionally, western blot and immunofluorescence analyses were performed to detect protein expression levels. RESULTS: We found that fasudil promoted neurite outgrowth in C17.2 cells in a time- and dose-dependent manner. The neurite-bearing C17.2 cells were differentiated by detecting the changes in neural and astrocytic markers after fasudil treatment through down-regulating Notch signalling. Previously, fasudil was reported to induce autophagy, which plays an important role in neural differentiation. However, both rapamycin, an autophagy inducer, and 3-methyl-adenine (3-MA), an autophagy inhibitor, had no effects on the fasudil-induced neurite outgrowth, suggesting that autophagy may be not involved in this process. CONCLUSION: In summary, fasudil could stimulate neurite outgrowth and differentiation in C17.2 cells by modulating Notch signalling but not autophagy.
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1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , Células-Tronco Neurais/efeitos dos fármacos , Neuritos/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Receptores Notch/metabolismo , Vasodilatadores/farmacologia , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Animais , Autofagia/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Linhagem Celular , Camundongos , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Neuritos/metabolismo , Neuritos/ultraestrutura , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais/efeitos dos fármacosRESUMO
Benzyl isothiocyanate (BITC) has been shown to have inhibitory potential for human glioma U87MG cells; however, the effect and mechanism were not fully clear. In the present study, we found that BITC could inhibit U87MG cell proliferation, adhesion, invasion, and vasculogenic mimicry (VM) formation potential and induce oxidative stress, apoptosis, and cell cycle arrest. We also found that the expression of proliferation, invasion, VM oxidative stress, apoptosis, and cell cycle-related gene and the activity of tumor-related signaling pathways, including protein kinase C (PKC) ζ and Akt/nuclear factor-kappa B (NF-κB) pathways, were suppressed by BITC treatment. We also explored the anti-tumor potential of BITC in vivo, and we found that BITC also could regulate the expression of tumor-related gene and angiogenesis in nude mice model. Finally, we optimized the BITC construction targeting alkylglycerone phosphate synthase (AGPS) by computer-aided design, and the derivants also showed anti-tumor potential in vitro.
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Alquil e Aril Transferases/biossíntese , Glioma/tratamento farmacológico , Glioma/genética , Isotiocianatos/administração & dosagem , Alquil e Aril Transferases/genética , Animais , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioma/patologia , Humanos , Camundongos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Oxidative stress and blood-brain barrier (BBB) disruption play important roles in cerebral ischemic pathogenesis and may represent targets for treatment. Earlier studies have shown that osthole, a main active constituent isolated from Cnidium monnieri (L.) Cusson, could be considered as an attractive therapeutic agent in the treatment of ischemic stroke. However, the mechanism underlying the protective effect remains vague. In this study we aimed to investigate the effect of osthole on transient cerebral ischemia as well as its mechanism(s) in C57 BL/6 J mice. Mice were subjected to transient global cerebral ischemia induced by bilateral common carotid artery occlusion for 25 min. Behavioral test was performed at 4 days after ischemia, followed by assessment of neuronal loss in hippocampal CA1 region. Osthole significantly improved the cognitive ability and enhanced the survival of pyramidal neurons in the CA1 region of mice after lesion. Further studies showed that osthole attenuated the permeation of BBB, which may contribute to antioxidative effect by increasing the superoxide dismutase activity and decreasing the malondialdehyde level in model mice. Further studies revealed that osthole obviously up-regulated the protein levels of nuclear factor erythroid 2-related factor 2/heme oxygenase 1 in HT22 cells. In conclusion, our findings indicated that osthole exerts neuroprotective effects against global cerebral ischemia injury by reducing oxidative stress injury and reserving the disruption of BBB, which may be attributed to elevating the protein levels of Nrf2 and HO-1.
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Barreira Hematoencefálica/efeitos dos fármacos , Cumarínicos/farmacologia , Ataque Isquêmico Transitório/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/farmacologia , Nootrópicos/farmacologia , Animais , Células Cultivadas , Heme Oxigenase-1/metabolismo , Hipocampo/patologia , Ataque Isquêmico Transitório/patologia , Ataque Isquêmico Transitório/psicologia , Masculino , Malondialdeído/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Superóxido Dismutase/metabolismoRESUMO
Berberine (BBR), one of the major constituents of Chinese herb Rhizoma coptidis, has been reported to exert beneficial effects to various diseases, including Alzheimer's disease (AD). In the present work, we aimed to investigate the effects of BBR on neuronal cell death induced by homocysteic acid (HCA), which was considered as a risk of AD. BBR significantly reduced HCA-induced reactive oxygen species (ROS) generation, lactate dehydrogenase release and subsequent cell death. LY294002, the PI3K inhibitor, blocked the protection as well as the up-regulation of Akt phosphorylation of BBR. Taken together, our results indicate that BBR protects HCA-induced HT-22 cell death partly via modulating Akt pathway, suggesting BBR may be a promising therapeutic agent for the treatment of HCA-related diseases, including AD.
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Berberina/uso terapêutico , Homocisteína/análogos & derivados , Proteínas do Tecido Nervoso/fisiologia , Neurônios/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/fisiologia , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Cromonas/farmacologia , Avaliação Pré-Clínica de Medicamentos , Homocisteína/toxicidade , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Morfolinas/farmacologia , Neurônios/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Fosforilação/efeitos dos fármacos , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismoRESUMO
Oxidative stress is closely related to the pathogenesis of neurodegenerative disorders such as Parkinson's disease. Carvedilol, a nonselective ß-adrenergic receptor blocker with pleiotropic activity has been shown to exert neuroprotective effect due to its antioxidant property. However, the neuroprotective mechanism of carvedilol is still not fully uncovered. The phosphotidylinositol 3-kinase (PI3K)/Akt signaling pathway plays key role in cell survival and the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway is the major cellular defense mechanism against oxidative stress. Here we investigated the effects of carvedilol on 6-hydroxydopamine (6-OHDA)-induced cell death as well as the Akt and Nrf2/ARE pathways in PC12 cells. We found that carvedilol significantly increased cell viability and decreased reactive oxygen species in PC12 cells exposed to 6-OHDA. Furthermore, carvedilol activated the Akt and Nrf2/ARE pathways in a concentration-dependent manner, and increased the protein levels of heme oxygenase-1(HO-1) and NAD(P)H quinone oxidoreductase-1(NQO-1), two downstream factors of the Nrf2/ARE pathway. In summary, our results indicate that carvedilol protects PC12 cells against 6-OHDA-induced neurotoxicity possibly through activating the Akt and Nrf2/ARE signaling pathways.
Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Carbazóis/farmacologia , Morte Celular/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Propanolaminas/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Carvedilol , Oxidopamina/toxicidade , Células PC12 , RatosRESUMO
Quinoline is high toxicity and difficult biodegradation in oil washing wastewater. Therefore, efficient removal of quinoline contaminant from water bodies poses a major challenge. Hence, Co quantum dot loaded N-doped porous carbon (CoNC) nanosheets grown in situ on carbon cloth were fabricated as cathode for the degradation of quinoline in electro-Fenton system. Under optimal conditions (c(Fe2+) = 0.5 mM, U = -0.3 V, pH = 3), quinoline was completely degraded within 15 min with superior apparent rate constant of 0.385 min-1, which was 19.6 times higher than that of the ZIF-L precursor, due to the abundance of Co QDs active sites and hydrophilicity and electrical conductivity of N-doped porous carbon. In addition, three reaction pathways for quinoline were deduced by combining Density Functional Theory (DFT) calculation and Liquid Chromatography-Mass Spectrometry (LC-MS). More importantly, in situ FTIR and free energy calculations were analyzed to reveal that pathway â as spontaneous reaction was the main reaction pathway. Finally, the toxicity of the intermediates was assessed with ECOSAR software and E. coli experiments, and the overall toxicity decreased during the degradation reactions. This work provides novel perspectives on environmental protection by designing in-situ grown cathodes through self-assembly method, thereby effectively purifying pollutants from wastewater.