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The continuous accumulation of microplastics in agricultural soils may affect the natural attenuation of oxygen-containing polycyclic aromatic hydrocarbons (OPAHs). The effects of low-density polyethylene (LDPE) microplastics with the spiking proportion of 1 % and 0.01 % in soils on the natural attenuation of OPAHs were investigated via soil microcosm experiments. The relation between the response of bacterial communities and OPAHs dissipation was also explored. The initial content of OPAHs in the soil was 34.6 mg·kg-1. The dissipation of OPAHs in the soil on day 14 was inhibited by LDPE. The contents of OPAHs in LDPE groups were higher than that in the control by 0.9-1.6 mg·kg-1, and the inhibition degree increased with the proportion of LDPE. The contents of OPAHs were not significantly different among groups on day 28, indicating that the inhibitory effect of LDPE disappeared. LDPE did not change the composition of the dominant taxa in the OPAHs-contaminated soil community but influenced the relative abundances of some dominant taxa. LDPE increased the relative abundance of Proteobacteria and Actinobacteria at the phylum level and decreased that of Bacillus and increased those of Micromonospora, Sphingomonas, and Nitrospira (potential degrading bacteria of LDPE and endogenous substances) at the genus level, all four of which were the main genera dominating intergroup community differences. LDPE changed the α and ß diversity of bacterial communities, but the extents were not significant. LDPE affected the function of the bacterial community, reducing the total abundance of PAHs-degrading genes and some degrading enzymes, inhibiting the growth of PAHs-degrading bacteria and thus interfering with the natural decay of OPAHs.
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Biodegradación Ambiental , Microplásticos , Hidrocarburos Policíclicos Aromáticos , Polietileno , Microbiología del Suelo , Contaminantes del Suelo , Hidrocarburos Policíclicos Aromáticos/análisis , Contaminantes del Suelo/metabolismo , Contaminantes del Suelo/análisis , Suelo/química , Bacterias/clasificación , Bacterias/metabolismo , Bacterias/crecimiento & desarrollo , Bacterias/efectos de los fármacos , Oxígeno/metabolismoRESUMEN
This study aimed to formulate reliable nomograms for predicting the outcomes of α-fetoprotein (AFP)-negative hepatocellular carcinoma (HCC) patients after chemotherapy. HCC patients with normal AFP expression who received chemotherapy were screened and evaluated from the surveillance, epidemiology, and end results database. The prognostic factors for predicting outcomes of HCC patients undergoing chemotherapy were chosen by analyzing the results of Cox analyses. Then, a nomogram integrating the prognostic factors was established. The discrimination ability of the nomogram was evaluated with computation of area under the curve (AUC) and calibration curve. A total of 2424 patients with AFP-negative HCC undergoing chemotherapy were identified. The median overall survival (OS) for HCC patients undergoing chemotherapy was 33 months. Age, race, pathologic grade, N stage, M stage, surgery, and lung metastases were significantly linked to OS. These relevant factors were incorporated into the nomogram. AUC values of the prognostic nomogram for 3- and 5-year OS were 0.696 and 0.706 in the training groups, which were superior to those of the tumor node metastasis (TNM) stage (0.641 and 0.671) in training groups. The calibration curves indicated a high consistency between the predicted probability of nomograms and the actual observation. The validation groups produced AUC values of 0.674 and 0.736 for 3- and 5-year OS, which were superior to those of the TNM stage (0.601 and 0.637) in validation groups. The results revealed significantly unfavorable OS in the high-risk group (P < .001). Nomograms to accurately predict the OS for AFP-negative HCC patients after chemotherapy were established and exhibited a more accurate predication than the conventional TNM staging system.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Nomogramas , Carcinoma Hepatocelular/tratamiento farmacológico , alfa-Fetoproteínas , Neoplasias Hepáticas/tratamiento farmacológico , Pronóstico , Programa de VERF , Estadificación de NeoplasiasRESUMEN
The genus Rabdosia is famous for the abundance of diverse and novel ent-kaurane diterpenoids. However, only a few ent-kauranoids have been discovered from R. flexicaulis since the investigation on its chemical constituents is not systematic. To find novel bioactive diterpenoids, the ethyl acetate extract of the above ground part of R. flexicaulis in Daofu County, Sichuan Province was obtained by column chromatography. One new compound and five known ones were identified as flexicaulin E(1), forrestin B(2), inf-lexarabdonin D(3), 7α-hydroxydehydroabietic acid(4), 15-hydroxydehydroabietic acid(5), and pomiferin F(6) by spectral techniques. Compounds 1-3 were the ent-kaurane diterpenoids isolated from this species for the first time. Compounds 4-6, aromatic abie-tanoids, were isolated from the genus Rabdosia for the first time.
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Diterpenos de Tipo Kaurano , Diterpenos , Isodon , Isodon/química , Estructura Molecular , Extractos Vegetales/químicaRESUMEN
INTRODUCTION: In order to find the early diagnostic markers of AIDS combined with TM infection, we detected and analyzed the serum exosomal miRNAs of AIDS patients with or without TM infection. MATERIALS AND METHODS: We profiled the expression levels of miRNAs via RNA sequencing in serum exosomes from the pooled samples of 17 AIDS patients combined without TM infection and 15 AIDS combined with TM infection patients. For external validation, we validated these results using real-time quantification polymerase chain reaction (qRT-PCR) in an independent cohort of 35 AIDS patients combined without TM infection and 33 AIDS combined with TM infection patients. Finally, bioinformatics was used to predict the target genes and pathways of meaningful miRNAs. RESULTS: A total of 131 serum exosomal miRNAs including 73 up-regulated and 59 down-regulated miRNAs were found to be differentially expressed (log2FC≥1 and FDR <0.01) in the two groups. A validation analysis revealed that three miRNAs (miR-192-5p, miR-194-5p and miR-1246) were upregulated in exosomes from AIDS combined with TM infection patients. ROC analyses showed that the AUC in combined diagnosis of the three miRNAs was 0.742, and the diagnostic sensitivity and specificity were 0.568 and 0.861, respectively. In the biological process analysis, all the 3 miRNAs were involved in transcription, DNA-templated and positive regulation of transcription from RNA polymerase II promoter. At the same time, the related pathways were involved in TGF-ß signaling pathway, AMPK signaling pathway, Wnt signaling pathway, MAPK signaling pathway, cGMP-PKG and cAMP signaling pathway, etc. CONCLUSION: miR-192-5p, miR-194-5p and miR-1246 in serum exosomes might be a potential biomarker for AIDS combined with TM infection patients, which may be involved in TGF-ß signaling pathway, AMPK signaling pathway, Wnt signaling pathway, MAPK signaling pathway, cGMP-PKG and cAMP signaling pathway, etc. Further research is needed on the biological functions and mechanisms of these miRNAs.
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BACKGROUND: Hepatocellular carcinoma (HCC) is the cause of an overwhelming number of cancer-related deaths across the world. Developing precise and noninvasive biomarkers is critical for diagnosing HCC. Our research was designed to explore potentially useful biomarkers of host peripheral blood mononuclear cell (PBMC) in HCC by integrating comprehensive bioinformatic analysis. METHODS: Gene expression data of PBMC in both healthy individuals and patients with HCC were extracted from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs). The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied to annotate the function of DEGs. Protein-protein interaction analysis was performed to screen the hub genes from DEGs. cBioportal database analysis was performed to assess the prognostic significance of hub genes. The Cancer Cell Line Encyclopedia (CCLE) and The Human Protein Atlas (HPA) database analyses were performed to confirm the expression levels of the hub genes in HCC cells and tissue. RESULTS: A total of 95 DEGs were screened. Results of the GO analysis revealed that DEGs were primarily involved in platelet degranulation, cytoplasm, and protein binding. Results of the KEGG analysis indicated that DEGs were primarily enriched in focal adhesion. Five genes, namely, myosin light chain kinase (MYLK), interleukin 1 beta (IL1B), phospholipase D1 (PLD1), cortactin (CTTN), and moesin (MSN), were identified as hub genes. A search in the CCLE and HPA database showed that the expression levels of these hub genes were remarkably increased in the HCC samples. Survival analysis revealed that the overexpression of MYLK, IL1B, and PLD1 may have a significant effect on HCC survival. The aberrant high expression levels of MYLK, IL1B, and PLD1 strongly indicated worse prognosis in patients with HCC. CONCLUSIONS: The identified hub genes may be closely linked with HCC tumorigenicity and may act as potentially useful biomarkers for the prognostic prediction of HCC in PBMC samples.
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Biomarcadores de Tumor/análisis , Carcinoma Hepatocelular/sangre , Protocolos Clínicos , Biomarcadores de Tumor/sangre , Análisis por Conglomerados , Biología Computacional/métodos , Perfilación de la Expresión Génica/métodos , Humanos , Leucocitos Mononucleares , Neoplasias Hepáticas/sangre , Metaanálisis como Asunto , Pronóstico , Mapas de Interacción de Proteínas/genética , Análisis de Supervivencia , Revisiones Sistemáticas como AsuntoRESUMEN
BACKGROUND: Researchers have discovered a large number of DNA methylation patterns in human cancer. These cancer-specific methylation patterns can provide information for the diagnosis, treatment, and prognosis of cancer. Methylation studies can find new biomarkers based on epigenetic analysis and apply these biomarkers to clinical oncology. Many studies on the association between RAASF1A methylation status and susceptibility to hepatitis B virus (HBV)/hepatitis C virus (HCV)-induced hepatocellular carcinoma (HCC) have reached controversial conclusions. Hence, the current review comprehensively assessed the correlation between Ras association domain family 1A (RASSF1A) methylation and the risk of the HCV/HBV-induced HCC. METHODS: The appropriated publications were extracted in EMBASE, PubMed, Web of Science, Cochrane Library, and China National Knowledge Infrastructure databases using STATA 5.0 software. The odds ratios (ORs) with 95 % confidence interval (95 % CI) of RASSF1A methylation were computed. RESULTS: A total of 1015 HBV/HCV-related HCC samples, 124 non-HBV/HCV-related HCC (NBNC-HCC) samples, and 1225 nontumorous controls were extracted and examined in this research. The frequency of the methylated RASSF1A in the HBV/HCV-related tumor cases displayed a significantly increased OR compared with the overall nontumor samples (OR = 19.372, 95 % CI = 11.060-33.931, P = 0.000). The frequency of the methylated RASSF1A in HBV/HCV-related neoplasm cases displayed a significantly increased OR compared with the non-HBV/HCV-related neoplasm (NBNC-neoplasm) samples (OR = 2.150, 95 % CI = 1.398-3.308, P = 0.000). Compared with normal, chronic hepatitis B or C, cirrhosis, and paracancerous samples, the pooled OR of the RASSF1A promoter methylation in the HBV/HCV-induced HCC samples was 62.785(95 % CI = 35.224-111.909), 25.07 (95 % CI = 13.85-45.36), 6.89 (95 % CI = 3.33-14.264) and 9.02 (95 % CI = 0.91-89.80), respectively. The rate of RASSF1A hypermethylation was robustly correlated with tumor size and vascular invasion, and the pooled OR was 0.346 (95 % CI = 0.210 - 0.569) and 0.081 (95 % CI = 0.022 - 0.303), respectively. CONCLUSION: Results showed robust associations between RASSF1A gene methylation in promoter region and enhanced HBV/HCV-related HCC susceptibility, thereby revealing that RASSF1A methylation status may serve as an important indicator for HCC oncogenesis.
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Carcinoma Hepatocelular/patología , Cirrosis Hepática/metabolismo , Neoplasias Hepáticas/patología , Proteínas Supresoras de Tumor/metabolismo , Carcinoma Hepatocelular/metabolismo , Metilación de ADN/fisiología , Hepatitis B Crónica/complicaciones , Humanos , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/metabolismo , Regiones Promotoras Genéticas/fisiologíaRESUMEN
The clinical role and potential molecular mechanisms of microRNA-449c-5p (miR-449c-5p) in hepatocellular carcinoma (HCC) tissues remains unclear. Combining multiple bioinformatic tools, we studied the miR-449c-5p expression levels in HCC tissues and explored possible target genes and related signaling pathways. First, miR-449c-5p expression data from microarrays provided by publicly available sources were mined and analyzed using various meta-analysis methods. Next, genes that were downregulated after miR-449c-5p mimic transfection into HCC cells were identified, and in silico methods were used to predict potential target genes. Several bioinformatic assessments were also performed to evaluate the possible signaling pathways of miR-449c-5p in HCC. Five microarrays were included in the current study, including GSE98269, GSE64632, GSE74618, GSE40744 and GSE57555. The standard mean difference was 0.44 (0.07-0.80), and the area under the curve was 0.68 (0.63-0.72), as assessed by meta-analyses, which consistently indicated the upregulation of miR-449c-5p in HCC tissues. A total of 2244 genes were downregulated after miR-449c-5p mimic transfection into an HCC cell line, while 5217 target genes were predicted by in silico methods. The overlap of these two gene pools led to a final group of 428 potential target genes of miR-449c-5p. These 428 potential target genes were primarily enriched in the homologous recombination pathway, which includes DNA Polymerase Delta 3 (POLD3). Data mining with Oncomine and the Human Protein Atlas showed a decreasing trend in POLD3 mRNA and protein levels in HCC tissue samples. This evidence suggests that miR-449c-5p could play an essential role in HCC through various pathways and that POLD3 could be a potential miR-449c-5p target. However, these in silico findings should be validated with further experiments.
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Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Regulación Neoplásica de la Expresión Génica/genética , Neoplasias Hepáticas/patología , MicroARNs/genética , Línea Celular Tumoral , Proliferación Celular/genética , Biología Computacional/métodos , ADN Polimerasa III/genética , Regulación hacia Abajo , Humanos , Neoplasias Hepáticas/genéticaRESUMEN
By employing a first-principles method, we conducted a thorough study on a novel cocrystal explosive 1 : 1 NTO : TZTN and gained insight into the interaction-structure-property interrelationship. Mulliken bond orders, Hirshfeld surfaces, intermolecular binding energies, packing coefficients, and oxygen balance were calculated to analyze the intermolecular interactions and structures of the cocrystal explosive. The cocrystallization of NTO and TZTN molecules enhances the intermolecular binding force, which drives the synthesis of the cocrystal. However, the cocrystallization decreases the molecular packing density along the closest packed directions, which reduces the density by 10.5% and deteriorates the oxygen balance. All of these lead to a reduction in the detonation performance compared to NTO explosives. We have also proposed a new method to evaluate the impact sensitivity according to the lattice dynamics calculation. The cocrystal explosive has a lower impact sensitivity than TZTN but higher than NTO, which agrees well with experiments.
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OBJECTIVE: To explore the effect of aluminum phosphate gel and Kangfuxin on esophageal pathology and expressions of interleukin-8 (IL-8) and prostaglandin E2 (PGE2) in rats with reflux esophagitis and explore the possible mechanisms. METHODS: Sixty SD rats were randomized into aluminum phosphate gel group (n=10), Kangfuxin group (n=10), aluminum phosphate gel+Kangfuxin group (n=10), model group (n=20), and control group (n=10). Except for those in the control group, all the rats were subjected to infusion of diluted lysolecithin with hydrochloric acid in the esophagus for 14 days. Ten rats in the model group and those in the control group were sacrificed to examine the pathological changes and contents of IL-8 and PGE2 in the esophagus using optical and electron microscopes and radioimmunoassay. The next day the rest rats were given corresponding treatments (saline in model group) administered into the esophagus on a daily basis for 14 days, after which esophageal pathologies and IL-8 and PGE2 contents were examined. RESULTS: The model rats showed obvious esophageal pathologies including inflammatory cell infiltration, vacuolar degeneration of the epithelial cells, esophageal erosion and even ulceration, with severe detachment of the epithelial cells. The rats in all the intervention groups showed lessened esophageal pathologies and lowered esophageal IL-8 and PGE2 contents compared with those in the model group. Esophageal mucosal injury index and IL-8 and PGE2 contents were all significantly lower in rats receiving combined treatment with aluminum phosphate and Kangfuxin than in those receiving either of the treatments (P<0.05). CONCLUSIONS: Both Kangfuxin and aluminum phosphate gel are effective in the treatment for reflux esophagitis induced by lysolecithin and hydrochloric acid, and their therapeutic effects are achieved possibly by reducing IL-8 and PGE2 levels in the esophagus.
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Compuestos de Aluminio/farmacología , Dinoprostona/metabolismo , Medicamentos Herbarios Chinos/farmacología , Esofagitis Péptica/metabolismo , Interleucina-8/metabolismo , Fosfatos/farmacología , Animales , Modelos Animales de Enfermedad , Esofagitis Péptica/tratamiento farmacológico , Esófago/efectos de los fármacos , Esófago/patología , Geles , Ratas , Ratas Sprague-DawleyRESUMEN
Two compounds belonging to a new group of diterpene alkaloids, kaurines A and B (1 and 2), and an alkaloid bearing a succinimide moiety (3) were obtained from Isodon rubescens. Their structures and absolute configurations were determined by spectroscopy and quantum-chemical computational (13)C NMR and ECD data analysis. These alkaloids differ from known diterpene alkaloids and diterpenoids and are presumably biosynthesized from ent-kaurane diterpenoids.
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Alcaloides/química , Alcaloides/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Diterpenos de Tipo Kaurano/química , Diterpenos de Tipo Kaurano/aislamiento & purificación , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Isodon/química , Alcaloides/farmacología , Antineoplásicos Fitogénicos/farmacología , Diterpenos de Tipo Kaurano/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/farmacología , Células HL-60 , Humanos , Células MCF-7 , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Componentes Aéreos de las Plantas/químicaRESUMEN
Verticinone, the main active component in F. hupehensis, exhibits potent antitussive and expectorant effects. Here, a LC-MS method was developed and applied to study the pharmacokinetics, tissue distribution and excretion of verticinone in rats, and its plasma protein binding in vitro. A significant gender difference in the pharmacokinetics of verticinone in rats was observed, as its absolute oral bioavailability in male and female rats was 45.8% and 2.74%, respectively. The relative bioavailability of verticinone was significantly lower in female rats as compared to male, following intragastrical (i.g.) and intravenous (i.v.) administration. After successive i.g. administration of verticinone, accumulation was observed in female rats but not in the male ones. The tissue distribution study showed that verticinone had a good tissue penetrability and a high tissue affinity in most studied tissues, except brain. After a 2 mg/kg oral dose, less than 4% of the dose was excreted as unchanged parent compound in male rats, and less than 1% in female rats, which indicated that verticinone was metabolized more extensively in female rats than in male rats.
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Cevanas/farmacocinética , Expectorantes/farmacocinética , Fritillaria/química , Extractos Vegetales/farmacocinética , Animales , Proteínas Sanguíneas/química , Cevanas/administración & dosificación , Cevanas/química , Evaluación Preclínica de Medicamentos , Expectorantes/administración & dosificación , Expectorantes/química , Femenino , Humanos , Masculino , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Ratas Sprague-Dawley , Distribución TisularRESUMEN
The in vivo effects of traditional herbal medicines are generally mediated by multiple bioactive components. The main constituents of Polygonum orientale L. are flavonoids such as orientin, vitexin, cynaroside, and quercitrin. The aim of this study was to develop and validate a method for characterizing these flavonoids, in order to better understand the pharmacokinetics and pharmacodynamics of P. orientale L. We used ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) to analyze the flavonoids. After precipitation of the proteins with methanol, the flavonoids were separated on a BEH C18 column (50mm×2.1mm, i.d., 1.7µm) by using an elution gradient of acetonitrile. Flavonoid content was determined using the multiple reaction monitoring (MRM) mode at m/z 449.2â329.2 for orientin, m/z 433.2â313.0 for vitexin, m/z 449.2â287.1 for cynaroside, m/z 449.2â303.4 for quercitrin, and m/z 417.0â267.0 for the internal standard, puerarin. Pharmacokinetics was assessed after intravenous administration of P. orientale L. extracts (POE) in Beagle dogs at a dose of 22, 44, or 88mg/kg. Analysis of the standard curves by linear regression revealed high linearity over a 243-fold dynamic range for the four flavonoids (the lower limit of quantitation values were 4-21ng/mL). The relative standard deviations of intra- and inter-day measurements were less than 15.1%, and the method was accurate to within -8.7% to 7.2%; the extraction recoveries from dog plasma were 70.6-89.3%, 69.8-88.7%, 72.5-85.7%, and 71.0-79.1% for orientin, vitexin, cynaroside, and quercitrin, respectively. Our results suggest non-linear pharmacokinetic characteristics with rapid clearance of the flavonoids. In conclusion, UPLC-ESI-MS/MS is a rapid and sensitive method for simultaneous quantification of multiple flavonoids from POE in dog plasma and is suitable for pharmacokinetic studies of herbal medicines.
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Cromatografía Líquida de Alta Presión/métodos , Flavonoides/sangre , Polygonum/química , Espectrometría de Masas en Tándem/métodos , Animales , Perros , Flavonoides/química , Flavonoides/farmacocinética , Modelos Lineales , Extractos Vegetales/química , Plantas Medicinales/química , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Espectrometría de Masa por Ionización de Electrospray/métodosRESUMEN
Three new ursane-type triterpenoids, 2α,3ß-dihydroxy-11α,12α-epoxy-urs-28,13ß-olide (1), 2α,3ß,24-trihydroxy-11α,12α-epoxy-urs-28,13ß-olide (2), and 2α,3α,24-trihydroxy-11,20(30)-dien-urs-28,13ß-olide (6), together with six known ursane-type triterpenoids (3-5, 7-9), were isolated from the EtOAc extract of the aerial parts of Isodon excisoides. Their structures were elucidated on the basis of 1D NMR and 2D NMR analyses as well as HRMS experiments.
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Medicamentos Herbarios Chinos/aislamiento & purificación , Isodon/química , Triterpenos/aislamiento & purificación , Medicamentos Herbarios Chinos/química , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Triterpenos/químicaRESUMEN
Five new ent-abietane diterpenoids, ent-abierubesins A-E (1-5), and two new ent-kauranoids, hubeirubesins A and B (6, 7), together with three known diterpenoids (8-10), were isolated from the aerial parts of Isodon rubescens. Their structures were identified by means of extensive spectroscopic analysis, and the absolute stereochemistry of 1 was determined by single-crystal X-ray diffraction experiment.
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Diterpenos de Tipo Kaurano/química , Isodon/química , Componentes Aéreos de las Plantas/química , Extractos Vegetales/química , Cristalografía por Rayos X , Diterpenos de Tipo Kaurano/aislamiento & purificación , Modelos Moleculares , Extractos Vegetales/aislamiento & purificaciónRESUMEN
AIMS: Bisphosphonate-related osteonecrosis of the jaws (BONJ) is a severe complication in patients on bisphosphonate therapy. The study was conducted to verify the association between CYP2C8 (rs1934951) polymorphism and BONJ predisposition. METHODS: The relative epidemiologic studies were identified in PubMed and Embase to conduct a meta-analysis using STATA. RESULTS: In the pooled analysis with multiple cancer types, patients carrying the CYP2C8 rs1934951 AA or AG genotype showed no significantly increased BONJ susceptibility compared with those carrying the wild GG genotype [dominant: odds ratio (OR) = 2.05, 95% confidence interval (CI) = 0.67-6.29, p = 0.209; recessive: OR = 1.88, 95% CI = 0.23-15.6, p = 0.560; AG vs. GG: OR = 2.07, 95% CI = 0.80-5.32, p = 0.133, and AA vs. GG: OR = 1.34, 95% CI = 0.48-3.74, p = 0.578]. A significant association between AA and AG genotypes of CYP2C8 (rs1934951) and BONJ risk was found in the subgroup analysis of multiple myeloma (dominant: OR = 5.77, 95% CI = 1.21-27.63, p = 0.028; AG vs. GG: OR = 5.02, 95% CI = 2.06-12.23, p = 0.001, and AA vs. GG: OR = 16.23, 95% CI = 1.72-78.7, p = 0.015). CONCLUSION: The results indicated that AA and AG genotypes of CYP2C8 (rs1934951) might be predictors for multiple myeloma patients at high risk to develop BONJ.
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Hidrocarburo de Aril Hidroxilasas/genética , Osteonecrosis de los Maxilares Asociada a Difosfonatos/genética , Difosfonatos/efectos adversos , Citocromo P-450 CYP2C8 , Humanos , Mieloma Múltiple/complicaciones , Mieloma Múltiple/genética , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
Three rare and new 11,20-epoxy-ent-kaurane diterpenoids, named jianshirubesins D-F (1-3), along with one known analogue (4), were isolated from the aerial parts of Isodon rubescens. Their structures were established by analysis of spectroscopic data. Found in the MTT assay to evaluate the cytotoxicity of compounds 1, 2, and 4, only 1 could selectively inhibit certain cell lines from proliferating. In addition, a simple structure-activity relationship discussion might suggest a new bioactive moiety, different from the α,ß-unsaturated ketone group.
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Antineoplásicos Fitogénicos/química , Diterpenos de Tipo Kaurano/química , Medicamentos Herbarios Chinos/química , Isodon , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Proliferación Celular , Diterpenos de Tipo Kaurano/aislamiento & purificación , Diterpenos de Tipo Kaurano/farmacología , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Células HL-60 , Humanos , Células MCF-7RESUMEN
Three new enmein-type diterpenoids, jianshirubesins A-C (1-3), together with ten known compounds, were isolated from the aerial parts of Isodon rubescens. Their structures were established by using spectroscopic methods, and the absolute configuration of compound 1 was confirmed by a single-crystal X-ray diffraction analysis. All compounds except 3 were evaluated for their in vitro cytotoxicity by MTT assay, and compounds 5 and 10 exhibited significant inhibitory ability on selected cell lines.
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Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Diterpenos/química , Diterpenos/farmacología , Isodon/química , Línea Celular Tumoral , Humanos , Modelos Moleculares , Estructura Molecular , Componentes Aéreos de las Plantas/químicaRESUMEN
Familial aggregation of hepatocellular carcinoma (HCC), the third leading cause of cancer death worldwide, has shown to be a common phenomenon. We investigated the association between the genetic background and HCC familial aggregation. Serum samples were collected from HCC family members and normal control family members for screening the differentially expressed protein peaks with the approach of surface-enhanced laser desorption ionization time-of-flight mass spectrometry. Potential genetically associated protein peaks were selected and further identified by matrix assisted laser desorption ionization-time of flight mass spectrometry. A panel of six protein peaks (m/z 6432.94, 8478.35, 9381.91, 17284.67, 17418.34, and 18111.04) were speculated to reflect the genetic susceptibility of HCC familial aggregation. Three of them (m/z 6432.94, 8478.35, and 9381.91) were selected to identify as the candidate proteins. Nine identified proteins, including mostly apolipoprotein family (ApoA1, ApoA2, ApoC3, ApoE) and serum amyloid A protein (SAA), were found overexpressed in the multiple HCC cases family members. The comparative proteomic profiles have suggested that genetic factors ought to be taken into account for familial aggregation of HCC.
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Carcinoma Hepatocelular/genética , Predisposición Genética a la Enfermedad/genética , Neoplasias Hepáticas/genética , Adulto , Carcinoma Hepatocelular/sangre , Femenino , Humanos , Lactante , Neoplasias Hepáticas/sangre , Masculino , Linaje , Proteómica/métodos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , TranscriptomaRESUMEN
OBJECTIVE: To assess the correlation between familial clustering of hepatocellular carcinoma (HCC) and the level of anti-P53 in human serum in Guangxi. METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to detect anti-P53 in 164 members from 20 HCC families and 164 members from non-cancer control families. Univariate analysis was performed to assess the correlation between seral level of P53 antibody and familial clustering of HCC. RESULTS: The level of P53 antibody was significantly higher in the members of HCC families than controls (Z=-3.04, P=0.002). After eliminating the interference of hepatitis B virus infection, this tendency still remains (P=0.011). And there was a significant difference between relatives of different degrees from HCC families (chi-square=11.593, P=0.021), with the expression of anti-P53 declining along with decrease in relationship coefficient. Furthermore, the number of individuals with high anti-P53 expression was also significantly greater in HCC families (95/164) than controls (71/164) (P=0.006). And the expression was rising along with the increasing HCC numbers (chi-square=16.068, P=0.000). Anti-P53 level was also greater in HCC families featuring sibling affection than parental affection (chi-square=12.679, P=0.002). Univariate analysis indicated that high expression of anti-P53 is a risk factor for development of HCC (OR=2.087, 95%CI: 1.270-3.431). CONCLUSION: High level of anti-P53 expression may be a factor for the clustering of HCC families in Guangxi, China.
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Anticuerpos Antineoplásicos/sangre , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/inmunología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/inmunología , Proteína p53 Supresora de Tumor/inmunología , Adolescente , Adulto , Anticuerpos Antineoplásicos/genética , Carcinoma Hepatocelular/sangre , Niño , China , Análisis por Conglomerados , Salud de la Familia , Femenino , Humanos , Neoplasias Hepáticas/sangre , Masculino , Factores de Riesgo , Adulto JovenRESUMEN
Two new guaianolides artemanomalides A and B were isolated from the aerial parts of Artemisia anomala S. Moore. Their structures were characterized as 2-oxo-5α, 10α-dihydroxy-guaia-3-en-1α, 6ß, 7α, 11ß H-12, 6-olide (1) and 8α-acetoxy-2-oxo-5α, 10α-dihydroxy-guaia-3, 11(13)-dien-1α, 6ß, 7αH-12, 6-olide (2) on the basis of extensive spectroscopic analyses. Compounds 1 and 2 showed inhibitory activities against COX-2 enzyme with IC(50) values of 8.8 and 3.6 µM.