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BACKGROUND: Liver fibrosis is a compensatory response during the tissue repair process in chronic liver injury, and finally leads to liver cirrhosis or even hepatocellular carcinoma. The pathogenesis of hepatic fibrosis is associated with the progressive accumulation of activated hepatic stellate cells (HSCs), which can transdifferentiate into myofibroblasts to produce an excess of the extracellular matrix (ECM). Myofibroblasts are the main source of the excessive ECM responsible for hepatic fibrosis. Therefore, activated hepatic stellate cells (aHSCs), the principal ECM producing cells in the injured liver, are a promising therapeutic target for the treatment of hepatic fibrosis. AIM: To explore the effect of taurine on aHSC proliferation and the mechanisms involved. METHODS: Human HSCs (LX-2) were randomly divided into five groups: Normal control group, platelet-derived growth factor-BB (PDGF-BB) (20 ng/mL) treated group, and low, medium, and high dosage of taurine (10 mmol/L, 50 mmol/L, and 100 mmol/L, respectively) with PDGF-BB (20 ng/mL) treated group. Cell Counting Kit-8 method was performed to evaluate the effect of taurine on the viability of aHSCs. Enzyme-linked immunosorbent assay was used to estimate the effect of taurine on the levels of reactive oxygen species (ROS), malondialdehyde, glutathione, and iron concentration. Transmission electron microscopy was applied to observe the effect of taurine on the autophagosomes and ferroptosis features in aHSCs. Quantitative real-time polymerase chain reaction and Western blot analysis were performed to detect the effect of taurine on the expression of α-SMA, Collagen I, Fibronectin 1, LC3B, ATG5, Beclin 1, PTGS2, SLC7A11, and p62. RESULTS: Taurine promoted the death of aHSCs and reduced the deposition of the ECM. Treatment with taurine could alleviate autophagy in HSCs to inhibit their activation, by decreasing autophagosome formation, downregulating LC3B and Beclin 1 protein expression, and upregulating p62 protein expression. Meanwhile, treatment with taurine triggered ferroptosis and ferritinophagy to eliminate aHSCs characterized by iron overload, lipid ROS accumulation, glutathione depletion, and lipid peroxidation. Furthermore, bioinformatics analysis demonstrated that taurine had a direct targeting effect on nuclear receptor coactivator 4, exhibiting the best average binding affinity of -20.99 kcal/mol. CONCLUSION: Taurine exerts therapeutic effects on liver fibrosis via mechanisms that involve inhibition of autophagy and trigger of ferroptosis and ferritinophagy in HSCs to eliminate aHSCs.
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Autofagia , Proliferación Celular , Ferroptosis , Células Estrelladas Hepáticas , Cirrosis Hepática , Especies Reactivas de Oxígeno , Taurina , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/patología , Humanos , Autofagia/efectos de los fármacos , Taurina/farmacología , Ferroptosis/efectos de los fármacos , Cirrosis Hepática/patología , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/metabolismo , Proliferación Celular/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Becaplermina/farmacología , Becaplermina/metabolismo , Línea Celular , Miofibroblastos/efectos de los fármacos , Miofibroblastos/metabolismo , Miofibroblastos/patología , Supervivencia Celular/efectos de los fármacos , Matriz Extracelular/metabolismo , Matriz Extracelular/efectos de los fármacos , Transducción de Señal/efectos de los fármacosRESUMEN
Directed transfer of carriers, akin to excited charges in photosynthesis, in semiconductors by structural design is challenging. Here, TiO2 nanosheets with interlayered sp2 carbon and titanium vacancies are obtained by low-temperature controlled oxidation calcination. The directed transfer of carriers from the excited position to Ti-vacancies to interlayered carbon is investigated and proven to greatly increase the charge transport efficiency. The TiO2/C obtained demonstrates excellent photocatalytic and photoelectrochemical activity and significant lithium/sodium ion storage performance. Further theoretical calculations reveal that the directional excited position/Ti-vacancies/interlayered carbon facilitate the spatial inside-out cascade electron transfer, resulting in high charge transfer kinetics.
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This study aimed to investigate the chemical constituents from the biological transformation of Hericium erinaceus and Artemisiae Annuae Herba(HQ biological transformation). The chemical constituents of ethyl acetate fraction of 75% ethanol extract in HQ biological transformation were separated and purified by silica gel and Sephadex LH-20 gel column chromatographies together with semi-preparative high performance liquid chromatography(HPLC). Their structures were identified by physicochemical properties, spectroscopic analysis, as well as comparisons with the data reported in literature. Nine compounds were isolated and identified as 2α-hydroxydeoxyartemisinin(1), 6ß-hydroxy-stigmast-4,22-dien-3-one(2), 3ß,5α-dihydroxy-ergosta-7,22-dien-6-one(3), friedelin(4), dankasterone(5), ergosterol endoperoxide(6), 3ß-hydroxy-5,9-epoxy-(22E,24R)-ergosta-7,22-dien-6-one(7), 3α,5α,9α-trihydroxy-(22E,24R)-ergosta-7,22-dien-6-one(8), and stigmast-3-one(9). Compound 1 was a new sesquiterpene lactone named 2α-hydroxy-deoxyartemisinin. The activity against Helicobacter pylori(Hp) of compounds 1-9 in vitro was determined by Kirby-Bauer disk diffusion method. The screening results showed compounds 1, 2 and 5 had certain anti-Hp activity.
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Fitoquímicos , Sesquiterpenos , Lactonas , Estructura MolecularRESUMEN
Invited for the cover of this issue are Xiao-Yu Yang and co-workers at Wuhan University of Technology, Heinrich-Heine-Universität Düsseldorf, University of the Witwatersrand, and Ben-Gurion University of the Negev. The image depicts Ti vacancies in TiO2 as powerful drivers of photo- and photo-electrocatalytic seawater splitting for hydrogen production. Read the full text of the article at 10.1002/chem.202101817.
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Photodriven seawater splitting is considered to be one of the most promising techniques for sustainable hydrogen production. However, the high salinity of seawater would deactivate catalysts and consume the photogenerated carriers. Metal vacancies in metal oxide semiconductors are critical to directed electron transfer and high salinity resistance; they are thus desirable but remain a challenge. We demonstrate a facile controllable calcination approach to synthesize TiO2 nanofibers with rich Ti vacancies with excellent photo/electro performances and long-time stability in photodriven seawater splitting, including photocatalysis and photo-electrocatalysis. Experimental measurements and theoretical calculations reveal the formation of titanium vacancies, as well as unidirectional electron trap and superior H+ adsorption ability for efficient charge transfer and resistance to corrosion by seawater. Therefore, atomic-/nanoscale characteristics and mechanism have been proposed to clarify the generation of titanium vacancies and the corresponding interfacial electron transfer.
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Molecular heterogeneity of hepatobiliary tumor including intertumoral and intratumoral disparity always leads to drug resistance. Here, seven hepatobiliary tumor organoids are generated to explore heterogeneity and evolution via single-cell RNA sequencing. HCC272 with high status of epithelia-mesenchymal transition proves broad-spectrum drug resistance. By examining the expression pattern of cancer stem cells markers (e.g., PROM1, CD44, and EPCAM), it is found that CD44 positive population may render drug resistance in HCC272. UMAP and pseudo-time analysis identify the intratumoral heterogeneity and distinct evolutionary trajectories, of which catenin beta-1 (CTNNB1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and nuclear paraspeckle assembly transcript 1 (NEAT1) advantage expression clusters are commonly shared across hepatobiliary organoids. CellphoneDB analysis further implies that metabolism advantage organoids with enrichment of hypoxia signal upregulate NEAT1 expression in CD44 subgroup and mediate drug resistance that relies on Jak-STAT pathway. Moreover, metabolism advantage clusters shared in several organoids have similar characteristic genes (GAPDH, NDRG1 (N-Myc downstream regulated 1), ALDOA, and CA9). The combination of GAPDH and NDRG1 is an independent risk factor and predictor for patient survival. This study delineates heterogeneity of hepatobiliary tumor organoids and proposes that the collaboration of intratumoral heterogenic subpopulations renders malignant phenotypes and drug resistance.
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Enfermedades del Sistema Digestivo/genética , Neoplasias Gastrointestinales/genética , Gliceraldehído-3-Fosfato Deshidrogenasa (Fosforilante)/genética , ARN Largo no Codificante/genética , beta Catenina/genética , Antígenos de Neoplasias/genética , Anhidrasa Carbónica IX/genética , Proteínas de Ciclo Celular/genética , Enfermedades del Sistema Digestivo/tratamiento farmacológico , Enfermedades del Sistema Digestivo/patología , Resistencia a Antineoplásicos/genética , Transición Epitelial-Mesenquimal/genética , Fructosa-Bifosfato Aldolasa/genética , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Gastrointestinales/patología , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Receptores de Hialuranos/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Quinasas Janus/genética , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Organoides/efectos de los fármacos , Organoides/metabolismo , Organoides/patología , RNA-Seq , Factores de Transcripción STAT/genética , Análisis de la Célula Individual , Transcriptoma/genéticaRESUMEN
A new bis-indole alkaloid, named arundaline (1), a new phenylpropanoid, named arundalcohol (2), and four known alkaloids, N-acetyltryptamine (3), trans-N-(p-coumaroyl)serotonin (4), trans-N-feruloylserotonin (5), and tuberosine B (6), were isolated from 70% aqueous ethanol extracts of the rhizomes of Arundo donax L. Their structures were elucidated by spectroscopic analysis and comparison of the data with literature values. Compounds 3-6 were isolated from the genus Arundo for the first time.
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Alcaloides/química , Poaceae/química , Etanol/química , Alcaloides Indólicos/química , Estructura Molecular , Extractos Vegetales/química , Rizoma/química , Serotonina/análogos & derivados , Serotonina/química , Triptaminas/químicaRESUMEN
The spike traits of wheat can directly affect yield. F2 and F2:3 lines derived from the cross of the multi-spikelet female 10-A and the uni-spikelet male BE89 were used to detect QTLs for spike length (SL), total spikelet number per spike (TSS), kernel number per spike (KNS) and thousand-kernel weight (TKW) in four different environments. A total of 1098 SNP and 5 SSR were used to construct genetic map of 2398.1 cM with the average distance of 2.2 cM between markers. A total of 11 QTLs were identified for spike traits, including three QTLs for SL, five QTLs for TSS, two QTLs for KNS and one QTL for TKW. The QTLs mapped to chromosomes 2D, 4A, 6A, 7A and 7B explained 8.2-37.8% of the phenotypic variation in single environment. The major QTL confidence interval with distance of 0.5 cM was located on chromosome 4A and detected in multiple environments, which can explain more than 30% of the phenotypic variation for SL, TSS and KNS. Combining IWGSC RefSeq v1.0 and RNA-seq data for 10-A and BE89, we identified 16 genes expressed on spike or grain in four QTL regions. These findings provide insights into improving wheat yield through increasing spikletes in wheat, particularly through the use of the multi-spikelet female 10-A for breeding.
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BACKGROUND AND AIMS: The relationship between serum cholesterol level and development of hepatocellular carcinoma (HCC) remains unclear. We investigated the effects of serum cholesterol level on development of liver tumors in mice. METHODS: We performed studies with C57BL/6J mice, mice with disruption of the low-density lipoprotein receptor gene (Ldlr-/-mice), and mice with conditional deletion of nature killer (NK) cells (NKdele mice). Some C57BL/6J and NKdele mice were given injections of diethylinitrosamine to induce liver tumor formation. Mice were placed on a normal diet (ND) or high-cholesterol diet (HCD) to induce high serum levels of cholesterol. We also studied mice with homozygous disruption of ApoE (ApoE-/- mice), which spontaneously develop high serum cholesterol. C57BL/6J and NKdele mice on the ND or HCD were implanted with Hep1-6 (mouse hepatoma) cells and growth of xenograft tumors and lung metastases were monitored. Blood samples were collected from mice and analyzed by biochemistry and flow cytometry; liver and tumor tissues were collected and analyzed by histology, immunohistochemistry, and RNA-sequencing analysis. NK cells were isolated from mice and analyzed for cholesterol content, lipid raft formation, immune signaling, and changes in functions. We obtained matched tumor tissues and blood samples from 30 patients with HCC and blood samples from 40 healthy volunteers; levels of cholesterol and cytotoxicity of NK cells were measured. RESULTS: C57BL/6J mice on HCD and ApoE-/- mice with high serum levels of cholesterol developed fewer and smaller liver tumors and lung metastases after diethylinitrosamine injection or implantation of Hep1-6 cells than mice on ND. Liver tumors from HCD-fed mice and ApoE-/- mice had increased numbers of NK cells compared to tumors from ND-fed mice. NKdele mice or mice with antibody-based depletion for NK cells showed similar tumor number and size in ND and HCD groups after diethylinitrosamine injection or implantation of Hep1-6 cells. NK cells isolated from C57BL/6J mice fed with HCD had increased expression of NK cell-activating receptors (natural cytotoxicity triggering receptor 1 and natural killer group 2, member D), markers of effector function (granzyme B and perforin), and cytokines and chemokines compared with NK cells from mice on ND; these NK cells also had enhanced cytotoxic activity against mouse hepatoma cells, accumulated cholesterol, increased lipid raft formation, and immune signaling activation. NK cells isolated from HCD-fed Ldlr-/- mice did not have increased cholesterol content or cytotoxic activity against mouse hepatoma cells compared with ND-fed Ldlr-/- mice. Serum levels of cholesterol correlated with number and activity of NK cells isolated from human HCCs. CONCLUSIONS: Mice with increased serum levels of cholesterol due to an HCD or genetic disruption of ApoE develop fewer and smaller tumors after injection of hepatoma cells or a chemical carcinogen. We found cholesterol to accumulate in NK cells and activate their effector functions against hepatoma cells. Strategies to increase cholesterol uptake by NK cells can be developed for treatment of HCC.
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Carcinoma Hepatocelular/inmunología , Colesterol/sangre , Células Asesinas Naturales/inmunología , Neoplasias Hepáticas/inmunología , Neoplasias Pulmonares/inmunología , Animales , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/secundario , Línea Celular Tumoral/trasplante , Colesterol/metabolismo , Dieta Aterogénica , Dietilnitrosamina/toxicidad , Modelos Animales de Enfermedad , Femenino , Humanos , Células Asesinas Naturales/metabolismo , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/secundario , Masculino , Ratones , Ratones Noqueados para ApoE , Receptores de LDL/genéticaRESUMEN
Correction for 'Synthesis of hydrophobic and hydrophilic TiO2 nanofluids for transformable surface wettability and photoactive coating' by Jie Hu et al., Chem. Commun., 2019, 55, 9275-9278.
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Two modified TiO2 nanofluids were developed, with either hydrophobic or hydrophilic properties. The hydrophobic TiO2 nanofluid, embedded in an organo-silyl salt, could be transformed into a hydrophilic TiO2 nanofluid by exchange of the chloride with an organo-sulphonate ion. Both modified TiO2 nanofluids exhibited high fluidity, thermal stability and photoactivity.
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BACKGROUND: Studies show that the antifibrotic mechanism of taurine may involve its inhibition of the activation and proliferation of hepatic stellate cells (HSCs). Since the molecular mechanism of taurine-mediated antifibrotic activity has not been fully unveiled and is little studied, it is imperative to use "omics" methods to systematically investigate the molecular mechanism by which taurine inhibits liver fibrosis. AIM: To establish a network including transcriptomic and protein-protein interaction data to elucidate the molecular mechanism of taurine-induced HSC apoptosis. METHODS: We used microarrays, bioinformatics, protein-protein interaction (PPI) network, and sub-modules to investigate taurine-induced changes in gene expression in human HSCs (LX-2). Subsequently, all of the differentially expressed genes (DEGs) were subjected to gene ontology function and Kyoto encyclopedia of genes and genomes pathway enrichment analysis. Furthermore, the interactions of DEGs were explored in a human PPI network, and sub-modules of the DEGs interaction network were analyzed using Cytoscape software. RESULTS: A total of 635 DEGs were identified in taurine-treated HSCs when compared with the controls. Of these, 304 genes were statistically significantly up-regulated, and 331 down-regulated. Most of these DEGs were mainly located on the membrane and extracellular region, and are involved in the biological processes of signal transduction, cell proliferation, positive regulation of extracellular regulated protein kinases 1 (ERK1) and ERK2 cascade, extrinsic apoptotic signaling pathway and so on. Fifteen significantly enriched pathways with DEGs were identified, including mitogen-activated protein kinase (MAPK) signaling pathway, peroxisome proliferators-activated receptor signaling pathway, estrogen signaling pathway, Th1 and Th2 cell differentiation, cyclic adenosine monophosphate signaling pathway and so on. By integrating the transcriptomics and human PPI data, nine critical genes, including MMP2, MMP9, MMP21, TIMP3, KLF10, CX3CR1, TGFB1, VEGFB, and EGF, were identified in the PPI network analysis. CONCLUSION: Taurine promotes the apoptosis of HSCs via up-regulating TGFB1 and then activating the p38 MAPK-JNK-Caspase9/8/3 pathway. These findings enhance the understanding of the molecular mechanism of taurine-induced HSC apoptosis and provide references for liver disorder therapy.
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Células Estrelladas Hepáticas/efectos de los fármacos , Cirrosis Hepática/tratamiento farmacológico , Sustancias Protectoras/farmacología , Mapas de Interacción de Proteínas/efectos de los fármacos , Taurina/farmacología , Línea Celular , Perfilación de la Expresión Génica , Redes Reguladoras de Genes/efectos de los fármacos , Humanos , Cirrosis Hepática/patología , Análisis de Secuencia por Matrices de Oligonucleótidos , Sustancias Protectoras/uso terapéutico , Taurina/uso terapéutico , Transcriptoma/efectos de los fármacosRESUMEN
Heme oxygenase (HO-1), which may be induced by Cobaltic protoporphyrin IX chloride (CoPPIX) or Rosiglitazone (Ros), is a neuroprotective agent that effectively reduces ischemic stroke. Previous studies have shown that the neuroprotective mechanisms of HO-1 are related to JNK signaling. The expression of HO-1 protects cells from death through the JNK signaling pathway. This study aimed to ascertain whether the neuroprotective effect of HO-1 depends on the assembly of the MLK3-MKK7-JNK3 signaling module scaffolded by JIP1 and further influences the JNK signal transmission through HO-1. Prior to the ischemia-reperfusion experiment, CoPPIX was injected through the lateral ventricle for 5 consecutive days or Ros was administered via intraperitoneal administration in the week prior to transient ischemia. Our results demonstrated that HO-1 could inhibit the assembly of the MLK3-MKK7-JNK3 signaling module scaffolded by JIP1 and could ultimately diminish the phosphorylation of JNK3. Furthermore, the inhibition of JNK3 phosphorylation downregulated the level of p-c-Jun and elevated neuronal cell death in the CA1 of the hippocampus. Taken together, these findings suggested that HO-1 could ameliorate brain injury by regulating the MLK3-MKK7-JNK3 signaling module, which was scaffolded by JIP1 and JNK signaling during cerebral ischemia/reperfusion.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Isquemia Encefálica/enzimología , Hemo Oxigenasa (Desciclizante)/metabolismo , Quinasas Quinasa Quinasa PAM/metabolismo , Proteína Quinasa 10 Activada por Mitógenos/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Animales , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/patología , Región CA1 Hipocampal/efectos de los fármacos , Región CA1 Hipocampal/enzimología , Región CA1 Hipocampal/patología , Muerte Celular/fisiología , Modelos Animales de Enfermedad , Regulación hacia Abajo , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Neuronas/efectos de los fármacos , Neuronas/enzimología , Neuronas/patología , Neuroprotección/efectos de los fármacos , Neuroprotección/fisiología , Fármacos Neuroprotectores/farmacología , Fosforilación , Proteínas Proto-Oncogénicas c-jun/metabolismo , Ratas Sprague-Dawley , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/enzimología , Daño por Reperfusión/patología , Rosiglitazona/farmacología , Proteina Quinasa Quinasa Quinasa 11 Activada por MitógenoRESUMEN
INTRODUCTION: It has well established that metabolic syndrome (MetS) can predict the risk of type 2 diabetes mellitus (T2DM) in some population groups. However, limited evidence is available regarding the predictive effect of MetS for incident T2DM in mainland Chinese population. METHODS: A 3-year cohort study was performed for 9735 Chinese without diabetes at baseline. MetS and its components were assessed by multivariable analysis using Cox regression. Prediction models were developed. Discrimination was assessed with area under the receiver operating characteristic curves (AUCs), and performance was assessed by a calibration curve. RESULTS: The 3-year cumulative incidence of T2DM was 11.29%. Baseline MetS was associated with an increased risk of T2DM after adjusting for age (HR = 2.68, 95% CI, 2.27-3.17 in males; HR = 2.59, 95% CI, 1.83-3.65 in females). Baseline MetS exhibited relatively high specificity (88% in males, 94% in females) and high negative predictive value (90% in males, 94% in females) but low sensitivity (36% in males, 23% in females) and low positive predictive value (31% in males and females) for predicting the 3-year risk of T2DM. AUCs, including age and components of MetS, for the prediction model were 0.779 (95% CI: 0.759-0.799) in males and 0.860 (95% CI: 0.836-0.883) in females. Calibration curves revealed good agreement between prediction and observation results in males; however, the model could overestimate the risk when the predicted probability is >40% in females. CONCLUSIONS: MetS predicts the risk of T2DM. The quantitative MetS-based prediction model for T2DM risk may improve preventive strategies for T2DM and present considerable public health benefits for the people in mainland China.
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AIM: To develop a reliable and simple method to identify important biological metabolites and relevant pathways for taurine in hepatic stellate cells (HSCs), in order to provide more data for taurine therapy. METHODS: All the biological samples were analyzed by using high-performance liquid chromatography-time electrospray ionization/quadrupole-time of flight mass spectrometry. Principal component analysis and partial least squares discriminant analysis were used to identify statistically different metabolites for taurine in HSCs, and metabolomic pathway analysis was used to do pathway analysis for taurine in HSCs. The chemical structure of the related metabolites and pathways was identified by comparing the m/z ratio and ion mode with the data obtained from free online databases. RESULTS: A total of 32 signiï¬cant differential endogenous metabolites were identified, which may be related to the mechanism of action of taurine in HSCs. Among the seven relevant pathways identified, sphingolipid metabolism pathway, glutathione metabolism pathway and thiamine metabolism pathway were found to be the most important metabolic pathways for taurine in HSCs. CONCLUSION: This study showed that there were distinct changes in biological metabolites of taurine in HSCs and three differential metabolic pathways including sphingolipid pathway, glutathione pathway and thiamine metabolism pathway might be of key importance in mediating the mechanism of action of taurine in HSCs.
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Células Estrelladas Hepáticas/metabolismo , Redes y Vías Metabólicas , Metabolómica/métodos , Taurina/metabolismo , Línea Celular , Cromatografía Líquida de Alta Presión , Análisis Discriminante , Humanos , Análisis de los Mínimos Cuadrados , Metabolismo de los Lípidos , Metaboloma , Análisis de Componente Principal , Espectrometría de Masa por Ionización de Electrospray , Esfingolípidos/metabolismoRESUMEN
A new quaiane-tgpe sesquiterpene was isolated from the 95% ethanol extract of the rhizomes of Acorus calamus by silica gel and sephadex LH-20 column chromatographic methods. Structure and absolute configuration of the sesquiterpene were elucidated by spectroscopic data and X-ray crystallographic analysis, and named as 1R,5R,7S-guaiane-4R,10R-diol-6-one.
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Acorus/química , Sesquiterpenos/aislamiento & purificación , Estructura Molecular , Extractos Vegetales/química , Rizoma/químicaRESUMEN
A novel tropoloisoquinoline alkaloid, neotatarine (1), was isolated from the 95% ethanol extract of the rhizome parts of Acorus calamus L. The chemical structure was unambiguously elucidated by spectroscopic and single-crystal X-ray diffraction analysis. Neotatarine (1) exhibited significantly inhibitory activity against Aß25 - 35 induced PC12 cell death with 2, 4 and 8 µm comparing with the assay control (P < 0.01).
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Acorus/química , Péptidos beta-Amiloides/antagonistas & inhibidores , Isoquinolinas/farmacología , Fragmentos de Péptidos/antagonistas & inhibidores , Tropolona/análogos & derivados , Animales , Muerte Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Isoquinolinas/química , Isoquinolinas/aislamiento & purificación , Estructura Molecular , Células PC12 , Ratas , Relación Estructura-Actividad , Tropolona/química , Tropolona/aislamiento & purificación , Tropolona/farmacologíaRESUMEN
BACKGROUND: The X protein (HBx) plays as a key role in hepatocarcinogenesis associated with hepatitis B virus (HBV) infections. The study aimed to figure out the role of Linc00152 in hepatocellular carcinoma (HCC) and the association between the expression levels of Linc00152 and HBx. METHODS: QRT-PCR assays were applied to analyzed the expression levels of Linc00152 and HBx. Kaplan-Meier survival curve was performed to identify the association between LINC00152 and the over survival time (OS) in HCC patients. Cell growth and invasion ability was evaluated by CCK8 cell proliferation and transwell invasion assays. Western-blot analysis was detected the protein expression. RNA immunoprecipitation (RIP), RNA-pull down and chromatin Immunoprecipitation (ChIP) assays was also been carried out. RESULTS: We demonstrated that LINC00152 expression in hepatocellular carcinoma (HCC) patients was significantly higher compared with adjacent non-tumour tissues and positively correlated with tumor size, HBV infection (HBsAg) and tumor number. Patient with hepatitis B virus (HBV) infection HCC was higher expression than that without HBV. Furthermore, the expression levels of Linc00152 were positively correlated with HBx expression in HCC tissues and higher Linc00152 expression levels were correlated with poor prognosis of HCC patients. In vitro, Linc00152 was up-regulated in Huh-7 and SM7721 cells after overexpression of HBx and down-regulated after silencing HBx. Furthermore, silencing Linc00152 suppressed the cell proliferation and invasion. Moreover, we found that Linc00152 inhibited the E-cadherin expression via interacting with EZH2 and promoted the Epithelial-mesenchymal transition (EMT) phenomenon in HCC cells. CONCLUSIONS: These results suggested that HBx enhanced LINC00152 expression and inhibition of LINC00152 could provide a therapeutic target for HCC.
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Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virología , Virus de la Hepatitis B/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virología , ARN Largo no Codificante/genética , Cadherinas/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Progresión de la Enfermedad , Regulación hacia Abajo/genética , Transición Epitelial-Mesenquimal/genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Células Hep G2 , Hepatitis B/genética , Hepatitis B/virología , Antígenos de Superficie de la Hepatitis B/genética , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Transducción de Señal/genética , Transactivadores/genética , Regulación hacia Arriba/genética , Proteínas Reguladoras y Accesorias ViralesRESUMEN
A new sesquiterpene, named neo-acorane A (1), and two known ones, acoric acid (2) and calamusin D (3), were isolated from a 95% ethanol extract of the rhizome parts of Acorus calamus L. Their structures were elucidated by spectroscopic methods, and the absolute configurations were determined by single-crystal X-ray diffraction analysis. Compounds 1 and 2 are nonisoprenoid sesquiterpenoids, likely biosynthesized from an acorane-type sesquiterpene by oxidative fission of the six- or five-membered ring. Moreover, compounds 1 (10 µM), 2 (5 µM and 10 µM) and 3 (10 µM) showed cell proliferation activity on the SK-N-BE (2) cell line.
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Acorus/química , Sesquiterpenos/química , Línea Celular , Proliferación Celular , Cristalografía por Rayos X , Humanos , Estructura Molecular , Extractos Vegetales/químicaRESUMEN
To study the chemical constituents and antimicrobial activity of Acori Calami Rhizoma. Components were isolated through various chromatographic methods and identified by spectroscopic data. The agar dilution method was adopted to analyze antimicrobial activity of the compounds in vitro.Eleven sesquiterpenoids were isolated, and indentified as 4ß,6ß-dihydroxy-1α,5ß(H)-guai-9-ene(1),4ß,6ß-dihydroxy-1α,5ß(H)-guai-10(14)-ene(2), teuclatriol(3), isocalamendiol(4), calamendiol(5), calamusin H(6), oxyphyllenodiols A(7), oplodiol(8), ananosmin(9), epishyobunone(10), and bullatantriol(11). Compound 9 was isolated from genus Acorus for the first time. Compounds 3, 7-9, and 11 had significantly antimicrobial activity. There were good sterilizing effects that the MBC of compound 9 to the four tested strains were 20.00 mgâ¢L⻹, and compound 11 to Pseudomonas aeruginosa was 12.50 mgâ¢L⻹.