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Oral microorganisms are closely related to oral health, the occurrence of some oral diseases is associated with changes in the oral microbiota, and many studies have demonstrated that traditional smoking can affect the oral microbial community. However, due to the short time since the emergence of e-cigarettes, fewer studies are comparing oral microorganisms for users of e-cigarettes versus cigarettes. We collected saliva from 40 non-smokers (NS), 46 traditional cigarette smokers (TS), and 27 e-cigarette consumers (EC), aged between 18 and 35 years. We performed 16S rRNA gene sequencing on the saliva samples collected to study the effects of e-cigarettes versus traditional cigarettes on the oral microbiome. The results showed that compared with the NS group, the alpha diversity of oral flora in saliva was altered in the TS group, with no significant change in the e-cigarette group. Compared with the NS and EC groups, the relative abundance of Actinomyces and Prevotella was increased in the TS group. However, compared with the NS and TS groups, the relative abundance of Veillonella was increased, and the relative abundance of Porphyromonas and Peptostreptococcus was decreased in the EC group. These results showed that both e-cigarettes and traditional cigarettes could alter the structure and composition of oral microbiota. The use of traditional cigarettes promotes the growth of some anaerobic bacteria, which may contribute to dental decay and bad breath over time. E-cigarettes have a different effect on the structure and composition of the oral microbial community compared to conventional cigarettes. In order to better understand the effects of e-cigarettes and traditional cigarettes on users' mouths, future studies will investigate the relationship between diseases such as dental caries and periodontitis and changes in oral microbial species levels.
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ß-Elemene, an important component of the volatile oil of Atractylodis macrocephala, has been widely utilized as an antitumor drug for over 20 years. However, the germacrene A synthase (GAS) genes responsible for the biosynthesis of ß-elemene in A. macrocephala were previously unidentified. In this study, two new AmGASs were identified from the A. macrocephala transcriptome, demonstrating their capability to convert farnesyl pyrophosphate into germacrene A, which subsequently synthesizes ß-elemene through Cope rearrangement. Additionally, two highly catalytic AmGAS1 mutations, I307A and E392A, resulted in a 2.23-fold and 1.57-fold increase in ß-elemene synthesis, respectively. Furthermore, precursor supply and fed-batch strategies were employed to enhance the precursor supply, resulting in ß-elemene yields of 7.3 mg/L and 33.3 mg/L, respectively. These findings identify a promising candidate GAS for ß-elemene biosynthesis and lay the foundation for further functional studies on terpene synthases in A. macrocephala.
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Sesquiterpenos de Germacrano , Sesquiterpenos , Sesquiterpenos/metabolismo , Sesquiterpenos/química , Sesquiterpenos de Germacrano/metabolismo , Alquil e Aril Transferases/metabolismo , Alquil e Aril Transferases/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fosfatos de Poli-Isoprenil/metabolismo , Atractylodes/metabolismo , Atractylodes/química , Atractylodes/genética , Vias Biossintéticas , TranscriptomaRESUMO
Kidney Renal Clear Cell Carcinoma (KIRC) is a malignant tumor that carries a substantial risk of morbidity and mortality. The MMP family assumes a crucial role in tumor invasion and metastasis. This study aimed to uncover the mechanistic relevance of the MMP gene family as a therapeutic target and diagnostic biomarker in Kidney Renal Clear Cell Carcinoma (KIRC) through a comprehensive approach encompassing both computational and molecular analyses. STRING, Cytoscape, UALCAN, GEPIA, OncoDB, HPA, cBioPortal, GSEA, TIMER, ENCORI, DrugBank, targeted bisulfite sequencing (bisulfite-seq), conventional PCR, Sanger sequencing, and RT-qPCR based analyses were used in the present study to analyze MMP gene family members to accurately determine a few hub genes that can be utilized as both therapeutic targets and diagnostic biomarkers for KIRC. By performing STRING and Cytohubba analyses of the 24 MMP gene family members, MMP2 (matrix metallopeptidase 2), MMP9 (matrix metallopeptidase 9), MMP12 (matrix metallopeptidase 12), and MMP16 (matrix metallopeptidase 16) genes were denoted as hub genes having highest degree scores. After analyzing MMP2, MMP9, MMP12, and MMP16 via various TCGA databases and RT-qPCR technique across clinical samples and KIRC cell lines, interestingly, all these hub genes were found significantly overexpressed at mRNA and protein levels in KIRC samples relative to controls. The notable effect of the up-regulated MMP2, MMP9, MMP12, and MMP16 was also documented on the overall survival (OS) of the KIRC patients. Moreover, targeted bisulfite-sequencing (bisulfite-seq) analysis revealed that promoter hypomethylation pattern was associated with up-regulation of hub genes (MMP2, MMP9, MMP12, and MMP16). In addition to this, hub genes were involved in various diverse oncogenic pathways. The MMP gene family members (MMP2, MMP9, MMP12, and MMP16) may serve as therapeutic targets and prognostic biomarkers in KIRC.
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Carcinoma de Células Renais , Neoplasias Renais , Sulfitos , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Metaloproteinase 12 da Matriz , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 16 da Matriz , Prognóstico , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/patologia , Rim/metabolismo , Rim/patologiaRESUMO
With the advancement of society, electronic cigarettes (e-cigarettes) have gained popularity among a growing number of individuals. While numerous toxicological studies have suggested that e-cigarettes are a safer alternative to traditional cigarettes, there is also a body of literature presenting contrasting findings. This in vitro study aimed to compare the effects of e-cigarettes and tobacco cigarettes (t-cigarettes) on RAW264.7 cells by using four e-cigarette aerosol extracts (ECA) and cigarette smoking extracts (CS) containing different nicotine concentrations. The results revealed that low concentration of nicotine in CS as well as in ECA with grape, watermelon, and cola flavors could promote cell viability. Conversely, high nicotine concentration in CS and ECA with four flavors decreased cell viability. Furthermore, our study demonstrated that CS significantly reduced the phagocytic capability of RAW264.7 cells and increased the levels of inflammatory cytokines (IL-6, TNF-α, and IL-1ß) and reactive oxygen species (ROS) compared to ECA. Overall, our findings indicate all four e-cigarettes induced less cytotoxicity to RAW264.7 cells and might be safer than t-cigarettes.
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Smoking increases the risk of a number of diseases, including cardiovascular, oral and lung diseases. E-cigarettes are gaining popularity among young people as an alternative to cigarettes, but there is debate over whether they are less harmful to the mouth than e-cigarettes. In this study, human gingival epithelial cells (HGECs) were treated with four commercially available e-cigarette aerosol condensates (ECAC) or commercially available generic cigarette smoke condensates (CSC) with different nicotine concentrations. Cell viability was determined by MTT assay. Cell apoptosis was observed by acridine orange (AO) and Hoechst33258 staining. The levels of type I collagen, matrix metalloproteinase (MMP-1, MMP-3), cyclooxygenase 2 and inflammatory factors were detected by ELISA and RT-PCR. Finally, ROS levels were analyzed by ROS staining. The different effects of CSC and ECAC on HGECs were compared. The results showed that higher nicotine concentration of CS significantly reduced the activity of HGECs. By contrast, all ECAC had no significant effect. The levels of matrix metalloproteinase, COX-2, and inflammatory factors were higher in HGECs treated with CSC than those treated with ECAC. In contrast, the level of type I collagen was higher in HGECs treated with ECAC than those treated with CSC. In conclusion, all four flavors of e-cigarettes were less toxic to HGE cells than tobacco, but further clinical studies are needed to determine whether e-cigarettes are less harmful to oral health than conventional cigarettes.
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Smoking increases the risk of a number of diseases, including cardiovascular, oral, and lung diseases. E-cigarettes are gaining popularity among young people as an alternative to cigarettes, but there is debate over whether they are less harmful to the mouth than e-cigarettes. In this study, human gingival epithelial cells (HGECs) were treated with four commercially available e-cigarette aerosol condensates (ECAC) or commercially available generic cigarette smoke condensates (CSC) with different nicotine concentrations. Cell viability was determined by MTT assay. Cell apoptosis was observed by acridine orange (AO) and Hoechst33258 staining. The levels of type I collagen, matrix metalloproteinase (MMP-1, MMP-3), cyclooxygenase 2, and inflammatory factors were detected by ELISA and RT-PCR. Finally, ROS levels were analyzed by ROS staining. The different effects of CSC and ECAC on HGECs were compared. The results showed that higher nicotine concentration of CS significantly reduced the activity of HGECs. By contrast, all ECAC had no significant effect. The levels of matrix metalloproteinase, COX-2, and inflammatory factors were higher in HGECs treated with CSC than those treated with ECAC. In contrast, the level of type I collagen was higher in HGECs treated with ECAC than those treated with CSC. In conclusion, all four flavors of e-cigarettes were less toxic to HGE cells than tobacco, but further clinical studies are needed to determine whether e-cigarettes are less harmful to oral health than conventional cigarettes.
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Pathogenic microorganisms in the environment are a great threat to global human health. The development of disinfection method with rapid and effective antibacterial properties is urgently needed. In this study, a biomimetic silver binding peptide AgBP2 was introduced to develop a facile synthesis of biocompatible Ag2 S quantum dots (QDs). The AgBP2 capped Ag2 S QDs exhibited excellent fluorescent emission in the second near-infrared (NIR-II) window, with physical stability and photostability in the aqueous phase. Under 808â nm NIR laser irradiation, AgBP2-Ag2 S QDs can serve not only as a photothermal agent to realize NIR photothermal conversion but also as a photocatalyst to generate reactive oxygen species (ROS). The obtained AgBP2-Ag2 S QDs achieved a highly effective disinfection efficacy of 99.06 % against Escherichia coli within 25â min of NIR irradiation, which was ascribed to the synergistic effects of photogenerated ROS during photocatalysis and hyperthermia. Our work demonstrated a promising strategy for efficient bacterial disinfection.
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Pontos Quânticos , Humanos , Pontos Quânticos/química , Desinfecção , Espécies Reativas de Oxigênio , Água/química , Peptídeos/farmacologia , BactériasRESUMO
There is a positive association between air pollution and lung cancer burden. This study aims to identify and examine lung cancer risks and mortality burdens associated with air pollutants, including PM10, NO2 and SO2, in seven eastern metropolises of China. The study population comprised a population from seven eastern metropolises of China. The yearly average values (YAV, µg/m3) of the PM10, NO2 and SO2 levels were extracted from China Statistical Yearbook (CSYB) for each selected city from 2006 to 2014. Data collected in the China Cancer Registry Annual Report (CCRAR) provide lung cancer incidence and mortality information. A two-level normal random intercept regression model was adopted to analyze the association between the lung cancer rates and individual air pollutant concentration within a five-year moving window of past exposure. The yearly average values of PM10, SO2 and NO2 significantly decreased from 2006 to 2014. Consistently, the male age-adjusted incidence rate (MAIR) and male age-adjusted mortality rate (MAMR) decreased significantly from 2006 to 2014.Air pollutants have a lag effect on lung cancer incidence and mortality for 2-3 years. NO2 has the significant association with MAIR (RR=1.57, 95% CI: 1.19-2.05, p=0.002), MAMR (RR=1.70, 95% CI: 1.32-2.18, p=0.0002) and female age-adjusted mortality rate (FAMR) (RR=1.27, 95% CI: 1.08-1.49, p=0.003). Our findings suggested that air pollutants may be related to the occurrence and mortality of lung cancer. NO2 was significantly associated with the risk of lung cancer, followed by SO2. Air pollutants have the strongest lag effect on the incidence and mortality of lung cancer within 2-3 years.
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In our previous study, we found that safrole oxide (SFO) could induce bone marrow mesenchymal stem cell differentiation into neuron-like cells. However, which kind of neuron cells was induced by SFO was unknown. Here, we found that SFO could induce BMSC differentiation into 5-hydroxytryptamine (5-HT) neuron-like cells. Microarray analysis of BMSCs treated with SFO for 6 h revealed a total of 35 genes changed more than twice. We selected G9a, a histone methyltransferase for further study. The upregulation of G9a was confirmed by RT-PCR and Western blot analysis. Small interfering RNA knockdown of G9a blocked SFO-induced BMSC differentiation. These results demonstrated that G9a was the pivotal factor in SFO-medicated 5-HT neuronal differentiation of BMSCs. Our findings provide a new clue for further investigating the gene control of BMSC differentiation into 5-HT neuron-like cells and provide a putative strategy for depression diseases therapies.
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Células-Tronco Mesenquimais , Serotonina , Animais , Células da Medula Óssea , Diferenciação Celular/genética , Células Cultivadas , Histona Metiltransferases , Neurônios , RNA Interferente Pequeno/genética , Safrol/análogos & derivados , Serotonina/farmacologiaRESUMO
With the development of the times, electronic cigarettes (e-cigarettes) are being received by more and more people. We compared the different effects of e-cigarettes and tobacco cigarettes on human umbilical vein endothelial cells (HUVECs) treated with the typical e-cigarette aerosol extracts (ECA) and cigarette smoking extracts (CS) sourced from commercial retail stores. HUVECs were treated with different kinds of ECA or CS with different nicotinic concentrations (0.03125, 0.125, 0.5, 2, 8, or 32 µg/mL). Cell viability was examined by the MTT assay. The cell apoptosis was investigated by acridine orange (AO) and Hoechst 33258 staining. The RT-PCR and western blot assays were used to analyze the adhesion molecules and inflammation cytokines released by HUVECs. Furthermore, the intracellular reactive oxygen species (ROS) was observed by fluorescence microscopy. Our data showed that the CS (nicotine concentration at 0.125 µg/mL could decrease the viability of HUVECs by 71%, but not the four kinds of ECA. The apoptotic ratio was about 32.5% in the CS group. No matter the levels of adhesion molecules, inflammation cytokines or ROS, they were higher in CS groups than in ECA groups. Overall, the four kinds of e-cigarettes induced significantly less cytotoxicity than the commercially available tobacco cigarettes in HUVECs. The CS showed the most severe impact on HUVECs. ECA might provide a harm reduction measure, especially in cardiovascular risk, after people switch from tobacco cigarettes to e-cigarettes.
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Fumar Cigarros , Sistemas Eletrônicos de Liberação de Nicotina , Aerossóis , Células Endoteliais da Veia Umbilical Humana , Humanos , Inflamação , Nicotiana/toxicidadeRESUMO
Brassinolide is a new type of steroidal hormone with strong activities, which is well known as an efficient and low-toxicity plant growth regulator for a long time. Because steroidal hormones have a wide application prospect, brassinosteroids have been gradually explored in pharmacology and animal cells in recent decades. Brassinolide could effectively reverse the resistance of human T lymphoblastoid cell line CCRF-VCR 1000 by inhibiting the effusion of drug transported by P-glycoprotein. Brassinosteroids could also accelerate wound healing by positively eliminating inflammation and stimulating reepithelialization of the reparation stage. The occurrence of cancer is a multistep process mediated by a variety of factors. Until now, cancer has always been one group of the major diseases that threaten human health. Many studies have found that brassinosteroids have attracted a great deal of potential as an anticancer agent in the treatment of cancer cells, and most of them exert anticancer activity by inducing apoptosis in cancer cells. There are few articles on the relationship between brassinosteroids and cancer so far. Accordingly, in this article, we summarized current research about the brassinosteroids and cancers. Through the review, researchers could know more about brassinosteroids which might become a new tool for the treatment of cancer in the future, and not only a plant hormone.
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Brassinosteroides , Neoplasias , Animais , Brassinosteroides/farmacologia , Colestanóis/metabolismo , Colestanóis/farmacologia , Neoplasias/tratamento farmacológico , Reguladores de Crescimento de Plantas/farmacologiaRESUMO
Cistanche deserticola Ma (cistanche) is a traditional herb with a wide range of therapeutic properties. However, no evidence of cistanche's effect on adipogenesis has been found. The effect of cistanche that promotes the adipogenesis of 3T3-L1 preadipocytes was proved by using MTT spectrophotometry, Nile Red staining, Oil Red O staining and transcriptome sequencing technology. The mRNA level of key transcription factors for adipogenesis such as PPAR, AP2 and LPL were examined by RT-PCR. The results showed that the intracellular lipid content in cistanche treated cells were notably increased when compared with the non-treated cells. Between the differentiation and cistanche treated groups, the expression of adipogenesis related genes such as grow hormone releasing hormone (Ghrp), BCL2/adenovirus E1B interacting protein 3 (Bnip3) and Gastric inhibitory polypeptide receptor (Gipr) were significantly increased. Our findings also verified that cistanche promoted adipogenesis, which was accompanied by up-regulated level of Bnip3 and PPAR. This study could uncover new signaling pathways involved in adipogenesis regulation.
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Adipogenia , Cistanche , Células 3T3-L1 , Adipócitos/metabolismo , Animais , Diferenciação Celular , Hormônios/metabolismo , Camundongos , PPAR gama/metabolismoRESUMO
BACKGROUND: Welsh onion constitutes an important crop due to its benefits in traditional medicine. Nitrogen is an important nutrient for plant growth and yield; however, little is known about its influence on the mechanisms of Welsh onion regulation genes. In this study, we introduced a gene expression and amino acid analysis of Welsh onion treated with different concentrations of nitrogen (N0, N1, and N2 at 0 kg/ha, 130 kg/ha, and 260 kg/ha, respectively). RESULTS: Approximately 1,665 genes were differentially regulated with different concentrations of nitrogen. Gene ontology enrichment analysis revealed that the genes involved in metabolic processes, protein biosynthesis, and transportation of amino acids were highly represented. KEGG analysis indicated that the pathways were related to amino acid metabolism, cysteine, beta-alanine, arginine, proline, and glutathione. Differential gene expression in response to varying nitrogen concentrations resulted in different amino acid content. A close relationship between gene expression and the content of amino acids was observed. CONCLUSIONS: This work examined the effects of nitrogen on gene expression and amino acid synthesis and provides important evidence on the efficient use of nitrogen in Welsh onion.
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Nitrogênio , Cebolas , Aminoácidos , Ontologia Genética , Cebolas/genética , TranscriptomaRESUMO
BACKGROUND: Allium fistulosum L. has good nutritional value and is cultivated worldwide as an efficacious traditional medicinal plant. Its biological activities are attributable to its phytochemicals. Nitrogen is an essential nutrient for plant growth and development; however, the effect of nitrogen levels on the level of active components in this species is not well understood. METHODS: In this study, using urea fertilizer, we investigated the effects of different nitrogen levels (N0, N1, and N2 at 0, 130, and 260 kg/ha, respectively) on the phytochemical constituents , and antioxidant and anticancer properties of A. fistulosum. RESULTS: The results suggested that nitrogen fertilizers have a significant effect on the level of total phenols and flavonoids. The analysis of the antioxidant capacity revealed that the lowest IC50 values corresponded to plants treated with the highest nitrogen concentration. Anticancer activity was investigated against cancer cell lines (HeLa and HepG2), and the extracts of A. fistulosum treated with a high nitrogen level showed the highest antiproliferative effect. Collectively, our results suggest that nitrogen fertilizer application enhanced the quality of A. fistulosum, particularly its health benefits.
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Renal cell carcinoma (RCC) is a major healthcare burden globally. Tumorderived extracellular vesicles (EVs) contribute to the formation of a prometastatic microenvironment. In the present study, we explored the role and mechanism of RCC cell 786Oderived EVs (786OEVs) in RCC. First, 786OEVs were extracted and identified, and EV internalization of RCC cells was observed. RCC cell malignant behaviors and long noncoding RNA (lncRNA) metastasisassociated lung adenocarcinoma transcript 1 (MALAT1) expression patterns were detected before and after 786OEV treatment. MALAT1 was intervened to evaluate RCC cell behaviors. The downstream mechanism involving MALAT1 was predicted. In addition, the relationship among MALAT1, transcription factor CP2 like 1 (TFCP2L1) and ETS protooncogene 1, transcription factor (ETS1) was analyzed. TFCP2L1 expression patterns were measured after 786OEV exposure. Tumor xenograft formation assay and lung metastasis model were adopted to verify the role of 786OEVs in vivo in RCC. It was found that 786OEVs could be internalized by RCC cells. 786OEVs promoted RCC cell malignant behaviors, accompanied by elevated MALAT1 expression levels. The 786OEVs with MALAT1 knockdown attenuated the promotive effect of sole 786OEVs on RCC cells. MALAT1 located ETS1 in the TFCP2L1 promoter and negatively regulated TFCP2L1, and ETS1 protein could specifically bind to MALAT1. 786OEVs enhanced the binding of ETS1 and the TFCP2L1 promoter and decreased TFCP2L1 expression. In vivo, 786OEVs promoted tumor growth and RCC lung metastasis, which was suppressed following inhibition of MALAT1. Our findings indicated that 786OEVs promoted RCC invasion and metastasis by transporting MALAT1 to promote the binding of transcription factor ETS1 and TFCP2L1 promoter.
Assuntos
Carcinoma de Células Renais/metabolismo , Vesículas Extracelulares/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/metabolismo , RNA Longo não Codificante/biossíntese , Animais , Biotinilação , Carcinogênese , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/genética , Biologia Computacional , Perfilação da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Metástase Neoplásica , Transplante de Neoplasias , Proteína Proto-Oncogênica c-ets-1/metabolismo , RNA Longo não Codificante/genética , Proteínas Repressoras/metabolismo , Transdução de SinaisRESUMO
Hedyotis diffusa polysaccharides, as the main component and an important bioactive substance of Hedyotis diffusa, are effective immunomodulators with various pharmacological activities, including antitumour, anti-inflammatory, antioxidant, anti-fatigue and immunity-enhancing activities. The total polysaccharides extracted from Hedyotis diffusa and Scutellaria barbata have great effects in treating liver cancer, gastric cancer, rectal cancer, glioma and nasopharyngeal carcinoma. Moreover, different materials and extraction methods result in differences in the structure and bioactivity of Hedyotis diffusa polysaccharides. Therefore, this paper summarizes the isolation, purification, structural characteristics, pharmacological activities, and combined action of Hedyotis diffusa polysaccharides to provide a reference for further study.
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Hedyotis/química , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Humanos , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Fatores Imunológicos/farmacologia , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
The activating receptor CD226 is expressed on lymphocytes, monocytes, and platelets and promotes anti-tumor immunity in pre-clinical models. Here, we examined the role of CD226 in the function of tumor-infiltrating lymphocytes (TILs) and resistance to immunotherapy. In murine tumors, a large proportion of CD8+ TILs had decreased surface expression of CD226 and exhibited features of dysfunction, whereas CD226hi TILs were highly functional. This correlation was seen also in TILs isolated from HNSCC patients. Mutation of CD226 at tyrosine 319 (Y319) led to increased CD226 surface expression, enhanced anti-tumor immunity and improved efficacy of immune checkpoint blockade (ICB). Mechanistically, tumor-derived CD155, the ligand for CD226, initiated phosphorylation of Y319 by Src kinases, thereby enabling ubiquitination of CD226 by CBL-B, internalization, and proteasomal degradation. In pre-treatment samples from melanoma patients, CD226+CD8+ T cells correlated with improved progression-free survival following ICB. Our findings argue for the development of therapies aimed at maintaining the expression of CD226.
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Antígenos de Diferenciação de Linfócitos T/imunologia , Linfócitos T CD8-Positivos/imunologia , Receptores Virais/imunologia , Animais , Linhagem Celular , Linhagem Celular Tumoral , Células HEK293 , Humanos , Inibidores de Checkpoint Imunológico/imunologia , Imunoterapia/métodos , Células Jurkat , Linfócitos do Interstício Tumoral/imunologia , Masculino , Melanoma/imunologia , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Hypochlorous acid (HOCl) is an important signaling molecule for cell survival. However, it has been reported that excessive HOCl contributes to a variety of diseases such as cancers. And in cancer cells, the level of HOCl is much higher than that in normal cells. Here a coumarin-based fluorescent probe 7-Diethylamino-3-(2,3-dihydro-1H-perimidin-2-yl)-chromen-2-one (CAN) was successfully developed for HOCl detection. The probe could be oxidized by HOCl to induce significant change in its fluorescence profile, which made it feasible for ratiometric detecting HOCl. CAN (below 1 µM) did not affect cell viability and had good capacity in ratiometric detection of HOCl in RAW 264.7 cells. CAN induced A549 apoptosis and inhibited tumor growth in vitro and in vivo. And CAN could decrease the chlorination activity of myeloperoxidase (MPO) in A549. These findings suggested that CAN (below 1 µM) would develop into a HOCl probe. High activity of MPO and level of HOCl might be helpful for A549 survival. A549 could be induced apoptosis by reducing the HOCl level by CAN. It implies a new anticancer strategy by targeting HOCl.
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Cumarínicos/síntese química , Corantes Fluorescentes/síntese química , Halogenação/efeitos dos fármacos , Ácido Hipocloroso/análise , Peroxidase/metabolismo , Células A549 , Animais , Apoptose , Cátions/química , Cumarínicos/metabolismo , Corantes Fluorescentes/metabolismo , Humanos , Ácido Hipocloroso/metabolismo , Metais/química , Camundongos , Imagem Óptica , Oxirredução , Células RAW 264.7 , Transdução de SinaisRESUMO
Potassium (K) is an essential nutrient, but levels of the free K ions (K+) in soil are often limiting, imposing a constant stress on plants. We have discovered a calcium (Ca2+)-dependent signalling network, consisting of two calcineurin B-like (CBL) Ca2+ sensors and a quartet of CBL-interacting protein kinases (CIPKs), which plays a key role in plant response to K+ starvation. The mutant plants lacking two CBLs (CBL2 and CBL3) were severely stunted under low-K conditions. Interestingly, the cbl2 cbl3 mutant was normal in K+ uptake but impaired in K+ remobilization from vacuoles. Four CIPKs-CIPK3, 9, 23 and 26-were identified as partners of CBL2 and CBL3 that together regulate K+ homeostasis through activating vacuolar K+ efflux to the cytoplasm. The vacuolar two-pore K+ (TPK) channels were directly activated by the vacuolar CBL-CIPK modules in a Ca2+-dependent manner, presenting a mechanism for the activation of vacuolar K+ remobilization that plays an important role in plant adaptation to K+ deficiency.
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Arabidopsis/metabolismo , Sinalização do Cálcio , Potássio/metabolismo , Adaptação Fisiológica , Arabidopsis/genética , Arabidopsis/fisiologia , Proteínas de Arabidopsis/genética , Proteínas de Ligação ao Cálcio/genética , Homeostase , Mutação , Fenótipo , Plantas Geneticamente Modificadas , Nicotiana/genética , Vacúolos/metabolismoRESUMO
In order to investigate the bond behavior of preplaced aggregate concrete-filled steel tube (CFT-PAC) columns and the difference of bond behavior between CFT-PAC columns and normal concrete-filled steel tube (CFT-NC) columns, a total of 11 columns were prepared and the push-out tests were conducted. The experimental parameters included the type of concrete (preplaced aggregate concrete and normal concrete), concrete strength (C40, C50 and C60), cross-section dimension (D = 219 mm, 299 mm and 351 mm) and the thickness of steel tube (t = 6 mm and 8 mm). The results indicated that the CTF-PAC columns had a similar load-slip curves with CFT-NC columns. The bond stresses of the CFT-PAC columns were higher than that of the PAC-NC columns at the same concrete strength. Increasing compressive strength of PAC increased the critical bond strength and bond strength of CFT-PAC columns. With an increase of the L/D ratio, both of the slip corresponding to peak load and bond strength of CFT-PAC columns exhibited an increasing trend. A rise in the D/t ratio led to a decrease in the bond stress of CFT-PAC columns and an increase in slip corresponding to the peak load of CFT-PAC columns. The proposed bond stress-slip relationship model considerably matched the bond stress-slip relationship of CFT-PAC columns.