RESUMO
Histone acetylation plays critical roles in chromatin remodeling, DNA repair, and epigenetic regulation of gene expression, but the underlying mechanisms are unclear. Proteasomes usually catalyze ATP- and polyubiquitin-dependent proteolysis. Here, we show that the proteasomes containing the activator PA200 catalyze the polyubiquitin-independent degradation of histones. Most proteasomes in mammalian testes ("spermatoproteasomes") contain a spermatid/sperm-specific α subunit α4 s/PSMA8 and/or the catalytic ß subunits of immunoproteasomes in addition to PA200. Deletion of PA200 in mice abolishes acetylation-dependent degradation of somatic core histones during DNA double-strand breaks and delays core histone disappearance in elongated spermatids. Purified PA200 greatly promotes ATP-independent proteasomal degradation of the acetylated core histones, but not polyubiquitinated proteins. Furthermore, acetylation on histones is required for their binding to the bromodomain-like regions in PA200 and its yeast ortholog, Blm10. Thus, PA200/Blm10 specifically targets the core histones for acetylation-mediated degradation by proteasomes, providing mechanisms by which acetylation regulates histone degradation, DNA repair, and spermatogenesis.
Assuntos
Reparo do DNA , Histonas/metabolismo , Proteínas Nucleares/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Espermatogênese , Testículo/metabolismo , Acetilação , Sequência de Aminoácidos , Animais , Quebras de DNA de Cadeia Dupla , Humanos , Masculino , Camundongos , Dados de Sequência Molecular , Proteínas Nucleares/química , Estrutura Terciária de Proteína , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Alinhamento de SequênciaRESUMO
The need for novel anti-thyroid cancer (TC) medications is urgent due to the rising incidence and metastatic rates of malignant TC. In this study, we investigated the effect of Polyphyllin VII (PPVII) to TC cells, and explored their potential mechanism. B-CPAP and TPC-1 cells, were used to analyze the antitumor activity of PPVII by quantifying cell growth and metastasis as well as to study the effect on epithelial mesenchymal transition (EMT). The results showed that PPVII dramatically reduced the capacity of B-CPAP and TPC-1 cells to proliferate and migrate in a dose-response manner. Following PPVII treatment of TC cells, the expression levels of E-cadherin progressively increased and were higher than the control group, while the expression levels of EMT-related genes Vimentin, N-cadherin, Slug, Zeb-1, and Foxe1 gradually declined and were lower than the control group. It was proposed that PPVII might prevent TC from undergoing EMT. The Foxe1 gene was shown to be significantly expressed in TC, and a statistically significant variation in Foxe1 expression was observed across clinical stages of the disease, according to a bioinformatics database study. There was a strong link between the expression of the Foxe1 gene and the EMT-related gene. In the meantime, TC cells' expression of Foxe1 can be inhibited by PPVII. In conclusion, our results showed that PPVII may as a potential medication for targeting EMT in thyroid cancer.
Assuntos
Caderinas , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Saponinas , Neoplasias da Glândula Tireoide , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Humanos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Proliferação de Células/efeitos dos fármacos , Caderinas/metabolismo , Caderinas/genética , Saponinas/farmacologia , Saponinas/uso terapêutico , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Relação Dose-Resposta a Droga , Expressão Gênica/efeitos dos fármacos , Terapia de Alvo Molecular , Antineoplásicos/farmacologiaRESUMO
Colorectal cancer (CRC) is a common human malignancy and the third leading cause of cancer-related death worldwide. Cancer stem cells (CSCs) were considered to play important roles in the genesis and development of many tumors. In recent years, it has been observed that leukemia inhibitory factor (LIF) might be involved in the regulation of stemness in cancer cells. In this study, we observed that LIF could increase the spheroid formation and stemness marker expression (inculding Nanog and SOX2) in CRC cell lines, such as HCT116 and Caco2 cells. Meanwhile, we also observed that LIF could upregulate LncRNA H19 expression via PI3K/AKT pathway. Knockdown of the expression of LncRNA H19 could decrease the spheroid formation and SOX2 expression in LIF-treated HCT116 and Caco2 cells, and thereby LncRNA H19 knockdown could compensate for the stemness enhancement effects induced by LIF. Our results indicated that LncRNA H19 might participate in the stemness promotion of LIF in CRC cells.
Assuntos
Neoplasias Colorretais , Fator Inibidor de Leucemia , Células-Tronco Neoplásicas , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fator Inibidor de Leucemia/metabolismo , Fator Inibidor de Leucemia/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Células CACO-2 , Células HCT116 , Regulação Neoplásica da Expressão Gênica , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Transdução de Sinais , Fosfatidilinositol 3-Quinases/metabolismoRESUMO
Ulcerative colitis (UC) is a relapsing inflammatory disease with a unique aetiology. The treatment of UC is challenging, and the current clinical therapeutics for colitis have limited efficacy. Thus, finding new and effective treatment options remains urgent. Baricitinib, an inhibitor of Janus kinase (JAK), has been clinically used to treat rheumatoid arthritis (RA). However, its potential effects on UC have not been fully elucidated. In this study, we aimed to explore the effects of baricitinib on UC and its underlying mechanism. Dextran sulphate sodium (DSS)-induced murine model of chronic colitis was used to investigate the intervention efficacy following oral administration of baricitinib. The levels of key cytokines, such as IL-6, IFN-γ and IL-17A, were determined. Moreover, western blotting for IκBα, p-IκBα, JAK2, p-JAK2, STAT3 and p-STAT3 protein expression was performed to investigate the associated signalling pathways. Our findings demonstrated that baricitinib can significantly relieve DSS-induced UC in mice. After baricitinib intervention, IL-6, IFN-γ and IL-17A levels were decreased both in vitro and in vivo. Moreover, the elevated expression levels of p-IκBα, p-JAK2, and p-STAT3 were significantly reduced after treatment. Collectively, these results suggest that baricitinib is a potential therapeutic agent for alleviation of DSS-induced colitis. This study provides a method for subsequent investigations on potential curative drugs development of the for colitis.
Assuntos
Azetidinas , Colite Ulcerativa , Colite , Purinas , Pirazóis , Sulfonamidas , Animais , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , NF-kappa B/metabolismo , Interleucina-17 , Inibidor de NF-kappaB alfa/uso terapêutico , Interleucina-6/metabolismo , Modelos Animais de Doenças , Colite/induzido quimicamente , Colite/tratamento farmacológicoRESUMO
γδT cells are important innate immune cells that are involved in the occurrence and development of autoimmune diseases such as systemic lupus erythematosus (SLE). Lupus nephritis (LN) is a serious complication of SLE, characterized by the accumulation of immune cells (including γδT cells) in the target organs to participate in the disease process. Therefore, clarifying how γδT cells chemotactically migrate to target organs may be a key to developing therapeutic methods against LN. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of chemokines in LN patients and healthy controls. Real-time polymerase chain reaction (RT-PCR) and flow cytometry were used to measure the expression of chemokine receptors on the surface of γδT cells. The chemotactic migration ability of γδT cells was detected by Transwell assay. Signalling pathway activation of γδT cells was detected by Automated Capillary Electrophoresis Immunoassay and flow cytometry. The serum levels of chemokines, including monocyte chemoattractant protein-1 (MCP-1) in LN patients, were significantly increased. CCR2, the receptor of MCP-1, was also highly expressed on the surface of peripheral γδT cells in LN patients. In addition, the exogenous addition of MCP-1 can enhance chemotactic migration of γδT cells in LN patients. MCP-1 could activate STAT3 signalling in LN patients' peripheral γδT cells. γδT cells might participate in the pathogenesis of LN through MCP-1/CCR2 axis. This finding provides new opportunities for developing treatment methods against LN by targeting MCP-1/CCR2 axis.
Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Quimiocina CCL2 , Transdução de Sinais , Ensaio de Imunoadsorção Enzimática , Receptores CCR2RESUMO
Immunotherapeutic strategies are recognized as promising treatment methods for colorectal cancer (CRC). αßT cell-mediated cytotoxicity is tolerated by cancer cells with low MHC class I expression; therefore, γδT cell-based cancer immunotherapy has generated increasing interest as a potential treatment option. To enhance the potency of γδT cell-based immunotherapy, the key factors involved in the regulation of γδT cells in CRC need to be identified along with devising ways to overcome potential hurdles. In this study, we observed that leukemia inhibitory factor (LIF), the serum level of which was highly increased in those with solid tumors, could specifically attenuate the cytotoxic function of peripheral γδT cells in patients with CRC. We observed that in patients with CRC, the expression levels of perforin and granzyme were significantly decreased in the recombinant human LIF (rhLIF)-treated peripheral γδT cells, whereas that of the LIF receptor (LIFR) was higher. The regulation of the cytotoxic function of the γδT cells by rhLIF was effected mainly through the STAT3 signaling pathway, which caused an increase in the expression levels of interleukin (IL)-17, COX-2, and prostaglandin E2 (PGE2). Our results revealed that rhLIF could impair the function of γδT cells in CRC patients by reducing the cytotoxic function and increasing the expression of tumor-promoting molecules, such as IL-17, COX-2, and PGE2.
Assuntos
Neoplasias Colorretais , Dinoprostona , Humanos , Fator Inibidor de Leucemia , Ciclo-Oxigenase 2 , Transdução de Sinais , Neoplasias Colorretais/terapia , Neoplasias Colorretais/patologiaRESUMO
In recent years, the application of chimeric antigen receptor T-cell (CAR-T) therapy based on gamma delta T (γδT) cells in hepatocellular carcinoma (HCC) immunotherapy has attracted more and more attention. However, specific antigens recognized by γδT cells are rarely identified, which has become the main restriction on such therapeutic application of γδT cells. In this report, we identified a new peptide and protein antigen recognized by γδT cells in HCC using our previous established strategy. First, we investigated the diversity of the γ9/δ2 T-cell immunorepertoire by sequence analyses of the expressed complementarity-determining region 3 (CDR3) in HCC patients. Then, we constructed γ9/δ2 T-cell receptor (TCR)-transfected cell lines expressing significant HCC CDR3 sequence and identified a series of peptides capable of binding to γδT cells specifically. Next, we identified, further tested and verified the biological functions of these peptides and their matched protein by bioinformatics analysis. We identified that the new protein hepatocyte growth factor-like protein, also called as macrophage-stimulating protein (MSP), and peptide HP1, not only bound to HCC-predominant γδTCR but also effectively activated γδT cells isolated from HCC patients. Moreover, they could stimulate γδT cells in peripheral blood from HCC patients to produce cytokines, which contributed to inhibiting HCC and played an important role in mediating cytotoxicity to HCC cell lines. In conclusion, we identified MSP and HP1, which showed potential as candidates for antigens recognized by γδT cells in HCC.
Assuntos
Carcinoma Hepatocelular/imunologia , Regiões Determinantes de Complementaridade/imunologia , Neoplasias Hepáticas/imunologia , Ativação Linfocitária/imunologia , Fragmentos de Peptídeos/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Linfócitos T/imunologia , Adulto , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Regiões Determinantes de Complementaridade/metabolismo , Feminino , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/metabolismo , Prognóstico , Receptores de Antígenos de Linfócitos T gama-delta/metabolismoRESUMO
The inflammatory process in systemic lupus erythematosus (SLE) affects many organs including the lungs. Chemokines are suggested to play important roles in the pathogenesis of SLE with pulmonary fibrosis (PF). In the present study, our objective is to evaluate the correlation between chemokines and PF in SLE patients. Transcriptome sequencing analysis was used to find the different expressed genes between SLE patients with PF and without PF. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of chemokines in SLE patients and healthy controls. Expression of CX3CR1 was measured by real-time polymerase chain reaction (PCR) and flow cytometer. Sixteen differentially chemokine genes were found to be associated to SLE with PF. Meanwhile, the upregulation of C-X3-C motif chemokine receptor 1 (CX3CR1) and its ligand, CX3C chemokine ligand 1 (CX3CL1) were observed in SLE patients with PF than that of SLE patients without PF and healthy control. Phenotypic analysis also showed that the surface expression of CX3CR1 increased in PBMCs from SLE patients with PF. Our observations indicated that CX3CL1/CX3CR1 axis is associated with PF in SLE. CX3CR1 might be a promising predictor of SLE with PF and the interactions between CX3CL1 and CX3CR1 might provide potential candidate target for the treatment of SLE with PF.
Assuntos
Receptor 1 de Quimiocina CX3C/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Fibrose Pulmonar/metabolismo , Adulto , Idoso , Quimiocinas/metabolismo , Feminino , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Transcriptoma/fisiologia , Regulação para Cima/fisiologia , Adulto JovemRESUMO
BACKGROUND: Chemokine levels in severe coronavirus disease 2019 (COVID-19) patients have been shown to be markedly elevated. But the role of chemokines in mild COVID-19 has not yet been established. According to the epidemiological statistics, most of the COVID-19 cases in Shiyan City, China, have been mild. The purpose of this study was to evaluate the level of chemokines in mild COVID-19 patients and explore the correlation between chemokines and host immune response. METHODS: In this study, we used an enzyme-linked immunosorbent assay to detect serum levels of chemokines in COVID-19 patients in Shiyan City. Expression of chemokine receptors and of other signaling molecules was measured by real-time polymerase chain reaction. RESULTS: We first demonstrated that COVID-19 patients, both sever and mild cases, are characterized by higher level of chemokines. Specifically, monocyte chemotactic protein 1 (MCP-1) is expressed at higher levels both in severe and mild cases of COVID-19. The receptor of MCP-1, C-C chemokine receptor type 2, was expressed at higher levels in mild COVID-19 patients. Finally, we observed a significant negative correlation between expression levels of interferon (IFN) regulatory factor 3 (IRF3) and serum levels of MCP-1 in mild COVID-19 patients. CONCLUSION: Higher expression of MCP-1 in mild COVID-19 patients might be correlated with inhibition of IFN signaling. The finding adds to our understanding of the immunopathological mechanisms of severe acute respiratory syndrome coronavirus 2 infection and provides potential therapeutic targets and strategies.
Assuntos
COVID-19/imunologia , Quimiocina CCL2/sangue , Quimiocinas/sangue , Interferon Tipo I/metabolismo , Adulto , COVID-19/metabolismo , COVID-19/fisiopatologia , China , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Fator Regulador 3 de Interferon/sangue , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Receptores CCR2/sangue , Transdução de Sinais/imunologiaRESUMO
γδ T cells play important roles in the development of rheumatoid arthritis (RA) through their antigen-presenting capacity, release of pro-inflammatory cytokines, immunomodulatory properties, interaction with CD4+ CD25+ Tregs and promotion of antibody production by helping B cells. Although prostaglandin E2 (PGE2) was proved to have the ability to enhance the antigen-presenting function of dendritic cells and IL-17 production of CD4+ αß T cells in RA, the role of PGE2 in γδ T cells from RA disease has not yet been clarified. The goal of this study was to determine the role of PGE2 in γδ T cells in RA. We first demonstrated that the population of γδT17 cells increased in patients with RA compared to healthy controls. Then, IL-17A level in patients with RA was shown to increase compared to healthy controls. After adding PGE2 to γδ T cells from patients with RA, the IL-17A level increased accordingly, and the expression of the costimulatory molecules, CD80 and CD86, on these cells also increased. These results suggest that PEG2 can increase the production of IL-17A and the expression of CD80 and CD86 on γδ T cells in patients with RA. These findings will benefit to explore new therapeutic targets for RA disease.
Assuntos
Artrite Reumatoide/etiologia , Artrite Reumatoide/metabolismo , Dinoprostona/metabolismo , Regulação da Expressão Gênica , Interleucina-17/biossíntese , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Adulto , Idoso , Artrite Reumatoide/patologia , Antígeno B7-1/genética , Antígeno B7-1/metabolismo , Antígeno B7-2/genética , Antígeno B7-2/metabolismo , Biomarcadores , Feminino , Humanos , Imunofenotipagem , Contagem de Linfócitos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND Freshly isolated mouse embryonic fibroblasts (MEFs) have great proliferation capacity but quickly enter senescent state after several rounds of cell cycle, a process called premature senescence. Cellular senescence can be induced by various stresses such as telomere erosion, DNA damage, and oncogenic signaling. But the contribution of other molecules, such as growth factors, to cellular senescence is incompletely understood. This study aimed to compare the gene expression difference between non-senescent and senescent MEFs to identify the key molecule(s) involved in the spontaneous senescence of MEFs. MATERIAL AND METHODS Primary MEFs were isolated from E12.5 pregnant C57/BL6 mice. The cells were continuously cultured in Dulbecco's Modified Eagle Medium for 9 passages. SA-ß-Gal staining was used as an indicator of cell senescence. The supernatant from primary MEFs (P1 medium) or Passage 6 MEFs (P6 medium) were used to culture freshly isolated MEFs to observe the effects on cell senescence state. Gene expression profiles of primary and senescent MEFs were investigated by RNA-Seq to find the key genes involved in cell senescence. Adipocyte differentiation assay was used to evaluate the stemness of MEFs cultured in FGF2-stimulated medium. RESULTS The senescence of MEFs cultured in the P1 medium was alleviated when compared to the P6 medium. Downregulation of FGF2 expression was revealed by RNA-Seq and further confirmed by real-time quantitative polymerase chain reaction and western blot. FGF2-stimulated medium also had anti-senescence function and could maintain the differentiation ability of MEFs. CONCLUSIONS The premature senescence of MEFs was at least partially caused by FGF2 deficiency. Exogenous FGF2 could alleviate the senescent phenotype.
Assuntos
Senescência Celular/fisiologia , Fator 2 de Crescimento de Fibroblastos/metabolismo , Fibroblastos/metabolismo , Animais , Diferenciação Celular , Proliferação de Células , Dano ao DNA , Embrião de Mamíferos/metabolismo , Feminino , Perfilação da Expressão Gênica , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Reação em Cadeia da Polimerase em Tempo Real , Transdução de SinaisRESUMO
Leukemia inhibitory factor (LIF), a member of the IL-6 cytokine family, is considered to be a pleiotropic cytokine and functions in both cell proliferation and differentiation. It is widely used in the culture of mouse embryonic stem cells and is implicated in the implantation of mouse model and possibly in humans. Great efforts have been made on the efficient generation of LIF to meet the requirement of this cytokine in biomedical research. However, because of the low expression level in the eukaryotic system and poor purification yields, recombinant human LIF has usually been expressed either as inclusion body or as fusion protein in E. coli (Escherichia coli). Here we introduce a simple method to express hLIF in a soluble form in E. coli and a subsequent purification method. The expression of hLIF was induced at a low temperature (16 °C) and most of the expressed hLIF was observed to be in a soluble form. Then by using three steps of chromatography, which could be easily scaled-up for industrial purposes, active untagged hLIF was purified with similar bioactivity compared to that of the commercial product. The endotoxin level of purified hLIF protein in our method was determined to be lower than 1EU/µg, which was also comparable to the commercial products. Furthermore, as hLIF was expressed in a soluble form, there was no need to develop the denaturation and renaturation methods. The yield of hLIF protein was evaluated to be approximately 0.7 mg hLIF from 1 g wet weight of E.coli in our method.
Assuntos
Escherichia coli/metabolismo , Expressão Gênica , Fator Inibidor de Leucemia , Escherichia coli/química , Escherichia coli/genética , Humanos , Fator Inibidor de Leucemia/biossíntese , Fator Inibidor de Leucemia/química , Fator Inibidor de Leucemia/genética , Fator Inibidor de Leucemia/isolamento & purificação , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificaçãoRESUMO
Poly (vinyl alcohol) (PVA), as an excellent degradable plastic feedstock, is limited by its diminishing stability in wet environment, low strength, thermal instability and nonopaque properties. In response to these concerns, a PVA/demethylated lignin-based supramolecular plastic (DPVA-HA-Fe-5) was designed and produced from PVA, demethylated lignin (DL), humic acid (HA) and Fe3+ ions via a simple casting method. As compared with pure PVA plastic, the tensile strength of DPVA-HA-Fe-5 were increased by 411 % to 410.61 MPa, and the breaking strain was increased by 149 % to 239.47 %. Notably, the hydrophobicity of DPVA-HA-Fe-5 was also significantly improved. Although in highly humid environment (stored in RH = 100 % for 10 days) or in alkaline organic solvent (stored in pyridine for 3 h), DPVA-HA-Fe-5 also showed excellent mechanical strengths of 302.9 and 222.99 MPa, respectively, which are equivalent or even superior to the most of commercial petroleum-based plastics. Moreover, the prepared plastics showed an outstanding UV resistance and shading performance, and about 98.3 % protection against ultraviolet radiation B rays and 90.7 % protection against visible light were obtained. In short, the introduction of lignin to improve the performance of PVA-based plastic is a feasible method, and it could facilitate the development of high-value utilization of lignin.
Assuntos
Lignina , Álcool de Polivinil , Resistência à Tração , Água , Lignina/química , Álcool de Polivinil/química , Água/química , Interações Hidrofóbicas e Hidrofílicas , Plásticos/química , Substâncias Húmicas/análise , Metilação , Raios UltravioletaRESUMO
With the development of renewable energy technologies, the demand for efficient energy storage systems is growing. Supercapacitors have attracted considerable attention as efficient electrical energy storage devices because of their excellent power density, fast charging and discharging capabilities, and long cycle life. Carbon nanofibers are widely used as electrode materials in supercapacitors because of their excellent mechanical properties, electrical conductivity, and light weight. Although environmental factors are increasingly driving the application of circular economy concepts in materials science, lignin is an underutilized but promising environmentally benign electrode material for supercapacitors. Lignin-based carbon nanofibers are ideal for preparing high-performance supercapacitor electrode materials owing to their unique chemical stability, abundance, and environmental friendliness. Electrospinning is a well-known technique for producing large quantities of uniform lignin-based nanofibers, and is the simplest method for the large-scale production of lignin-based carbon nanofibers with specific diameters. This paper reviews the latest research progress in the preparation of lignin-based carbon nanofibers using the electrospinning technology, discusses the prospects of their application in supercapacitors, and analyzes the current challenges and future development directions. This is expected to have an enlightening effect on subsequent research.
Assuntos
Carbono , Capacitância Elétrica , Lignina , Nanofibras , Lignina/química , Nanofibras/química , Carbono/química , Eletrodos , Técnicas Eletroquímicas/métodosRESUMO
BACKGROUND: Liver cancer is one of the most prevalent forms of cancer of the digestive system in our country. The most common subtype of this disease is hepatocellular carcinoma (HCC). Currently, treatment options for HCC patients include surgical resection, liver transplantation, radiofrequency ablation, chemoembolization, and biologic-targeted therapy. However, the efficacy of these treatments is suboptimal, as they are prone to drug resistance, metastasis, spread, and recurrence. These attributes are closely related to cancer stem cells (CSCs). Therefore, the utilization of drugs targeting CSCs may effectively inhibit the development and recurrence of HCC. METHODS: HepG2 and Huh7 cells were used to analyze the antitumor activity of emodin by quantifying cell growth and metastasis, as well as to study its effect on stemness. RESULTS: Emodin effectively suppressed the growth and movement of HCC cells. Emodin also significantly inhibited the proliferation of CD44-positive hepatoma cells. CONCLUSION: Emodin shows promise as a potential therapeutic agent for HCC by targeting CD44-- positive hepatoma cells.
Assuntos
Carcinoma Hepatocelular , Proliferação de Células , Emodina , Receptores de Hialuronatos , Neoplasias Hepáticas , Células-Tronco Neoplásicas , Humanos , Emodina/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Receptores de Hialuronatos/metabolismo , Proliferação de Células/efeitos dos fármacos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Células Hep G2 , Movimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Antineoplásicos/farmacologiaRESUMO
Necroptosis is a newly-identified form of gene-regulated cell necrosis that is increasingly considered to be a pathway associated with human pathophysiological conditions. Cells undergoing necroptosis exhibit necrotic phenotypes, including disruption of the plasma membrane integrity, organelle swelling, and cytolysis. Accumulating evidence suggests that trophoblast necroptosis plays a complex role in preeclampsia (PE). However, the exact pathogenesis remains unclear. Its unique mechanisms of action in various diseases are expected to provide prospects for the treatment of PE. Therefore, it is necessary to further explore its molecular mechanism in PE in order to identify potential therapeutic options. This review examines the current knowledge regarding the role and mechanisms of necroptosis in PE and provides a theoretical basis for new therapeutic targets for PE.
Assuntos
Pré-Eclâmpsia , Gravidez , Feminino , Humanos , Pré-Eclâmpsia/patologia , Necroptose , Apoptose/genética , Necrose/metabolismo , Morte Celular/fisiologiaRESUMO
Natural gas is regarded as the main transition energy under the carbon-neutral strategy and its main consumers are Organization for Economic Cooperation and Development countries, accounting for 44.5% of world consumption in 2021. In order to investigate the effects of technology, industry, and regions on natural gas consumption, 12 major Organization for Economic Cooperation and Development countries from three different country groups were selected in this paper to explore the consumption change. Firstly, the Logarithmetic Mean Divisia Index model is adopted to find out the driving factors. Then, the Tapio model is used to consider the decoupling state between natural gas consumption and economic growth. The results can be concluded as follows: (a) From 2000 to 2020, the technological progress effect has the biggest values of -148.86, followed by the industrial structure effect and the regional scale effect, with values of - 37.04 and 29.42, respectively. (b) From the perspective of industry view, these three effects have the largest impact on the secondary industry, followed by the tertiary industry and primary industry; (c) the regional scale effect has a positive effect on most countries, and the industrial structure effect and the regional scale effect have a negative effect on most countries; (d) the decoupling state vary differently in countries with different groups. Therefore, we concluded two policy recommendations for nature gas reduction: (a) Technological innovation is the most effective way for reducing natural gas consumption; (b) Industrial structure optimization can help save natural gas consumption.
RESUMO
Recently, the application of lignin activation by demethylation to improve reactivity and enrich multiple functions has intensively attracted attention. However, it is still challenge up to now due to the low reactivity and complexity of lignin structure. Here, an effective demethylation way was explored by microwave-assisted method for substantially enhancing the hydroxyl (-OH) content and retaining the structure of lignin. Then, the optimum demethylated lignin was used to removal heavy metal ions and promote wound healing, respectively. In detail, for microwave-assisted demethylated poplar lignin (M-DPOL), the contents of phenolic (Ar-OH) and total hydroxyl (Tot-OH) groups reached the maximum for 60 min at 90 °C in DMF with 7.38 and 9.13 mmol/g, respectively. After demethylation, with this M-DPOL as lignin-based adsorbent, the maximum adsorption capacity (Qmax) for Pb2+ ions reached 104.16 mg/g. Based on the isotherm, kinetic and thermodynamic models analyses, the chemisorption occurred in monolayer on the surface of M-DPOL, and all adsorption processes were endothermic and spontaneous. Meanwhile, M-DPOL as a wound dressing had excellent antioxidant property, outstanding bactericidal activity and remarkable biocompatibility, suggesting that it did not interfere with cell proliferation. Besides, the wounded rats treated with M-DPOL significantly promoted its formation of re-epithelialization and wound healing of full-thickness skin defects. Overall, microwave-assisted method of demethylated lignin can offer great advantages for heavy metal ions removal and wound care dressing, which facilitates high value application of lignin.
Assuntos
Metais Pesados , Poluentes Químicos da Água , Ratos , Animais , Lignina/química , Adsorção , Metais Pesados/química , Íons , Bandagens , Poluentes Químicos da Água/química , CinéticaRESUMO
The fabrication of pH-sensitive lignin-based materials has received considerable attention in various fields, such as biomass refining, pharmaceuticals, and detecting techniques. However, the pH-sensitive mechanism of these materials is usually depending on the hydroxyl or carboxyl content in the lignin structure, which hinders the further development of these smart materials. Here, a pH-sensitive lignin-based polymer with a novel pH-sensitive mechanism was constructed by establishing ester bonds between lignin and the active molecular 8-hydroxyquinoline (8HQ). The structure of the produced pH-sensitive lignin-based polymer was comprehensively characterized. The substituted degree of 8HQ was tested up to 46.6% sensitivity, and the sustained release performance of 8HQ was confirmed by the dialysis method, the sensitivity of which was found to be 60 times slower compared with the physical mixed sample. Moreover, the obtained pH-sensitive lignin-based polymer showed an excellent pH sensitivity, and the released amount of 8HQ under an alkaline condition (pH = 8) was obviously higher than that under an acidic condition (pH = 3 and 5). This work provides a new paradigm for the high-value utilization of lignin and a theory guidance for the fabrication of novel pH-sensitive lignin-based polymers.
RESUMO
Recently, multifunctional lignin-based materials are gaining more and more attention due to their great potential for low-cost and sustainability. In this work, to obtain both an excellent supercapacitor electrode and an outstanding electromagnetic wave (EMW) absorber, a series of multifunctional nitrogen-sulphur (N-S) co-doped lignin-based carbon magnetic nanoparticles (LCMNPs) had been successfully prepared through Mannich reaction at different carbonization temperature. As compared with the directly carbonized lignin carbon (LC), LCMNPs had more nano-size structure and higher specific surface area. Meanwhile, with the increase of carbonization temperature, the graphitization of the LCMNPs could also be effectively improved. Therefore, LCMNPs-800 displayed the best performance advantages. For the electric double layer capacitor (EDLC), the optimal specific capacitance of LCMNPs-800 reached 154.2 F/g, and the capacitance retention after 5000 cycles was as high as 98.14 %. When the power density was 2204.76 W/kg, the energy density achieved 33.81 Wh/kg. In addition, N-S co-doped LCMNPs also exhibited strong electromagnetic wave absorption (EMWA) ability, whose the minimum reflection loss (RL) value of LCMNPs-800 was realized -46.61 dB at 6.01 GHz with an thickness of 4.0 mm, and the effective absorption bandwidth (EAB) was up to 2.11 GHz ranging from 5.10 to 7.21 GHz, which could cover the C-band. Overall, this green and sustainable approach is a promising strategy for the preparation of high-performance multifunctional lignin-based materials.