Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 39
Filtrar
1.
Bioorg Chem ; 151: 107691, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39116524

RESUMO

Ten new B-ring aromatized 6/6/6-tricyclic dearomatized benzocogeijerene-based meroterpenoids with unusual methyl 1,2-shift or demethylation (2-9b), and two new geranylquinol derivatives (1 and 10), together with two known compounds (11 and 12), were isolated from the roots of Arnebia euchroma. Their structures were elucidated by extensive spectroscopic methods, X-ray diffraction crystallography, and ECD calculations. The plausible biosynthetic pathways including the unusual methyl 1,2-shfit and demethylation for B-ring aromatized 6/6/6-tricyclic meroterpenoids were discussed. Compounds 1, 2, 5, 6, 11, and 12 showed significant cardioprotective activities comparable to diltiazem against isoprenaline (ISO)-induced H9C2 cell damage in vitro. Compound 11 probably exerted heart-protective effect on ISO-induced H9C2 cells by modulating the PI3K-AKT-mTOR pathway, reducing excessive autophagy, and decreasing myocardial apoptosis.


Assuntos
Apoptose , Autofagia , Boraginaceae , Miócitos Cardíacos , Terpenos , Apoptose/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Autofagia/efeitos dos fármacos , Boraginaceae/química , Ratos , Terpenos/farmacologia , Terpenos/química , Terpenos/isolamento & purificação , Animais , Estrutura Molecular , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Insuficiência Cardíaca/tratamento farmacológico , Cardiotônicos/farmacologia , Cardiotônicos/química , Cardiotônicos/isolamento & purificação , Linhagem Celular
2.
J Med Virol ; 95(8): e28980, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37522289

RESUMO

Hepatitis B virus (HBV) infection and integration are important for hepatocellular carcinoma (HCC) initiation and progression, while disease mechanisms are still largely elusive. Here, we combined bulk and single-cell sequencing technologies to tackle the disease mechanisms of HBV-related HCC. We observed high HBV mutation rate and diversity only in tumors without HBV integration. We identified human somatic risk loci for HBV integration (VIMs). Transcription factors (TFs) enriched in VIMs were involved in DNA repair and androgen receptor (AR) signaling. Aberration of AR signaling was further observed by single-cell regulon analysis in HBV-infected hepatocytes, which showed remarkable interactions between AR and the complement system that, together with the X-linked ZXDB regulon that contains albumin (ALB), probably contribute to HCC male predominance. Complement system dysregulation caused by HBV infection was further confirmed by analyses of single-cell copy numbers and cell-cell communications. Finally, HBV infection-associated immune cells presented critical defects, including TXNIP in T cells, TYROBP in NK cells, and the X-linked TIMP1 in monocytes. We further experimentally validated our findings in multiple independent patient cohorts. Collectively, our work shed light on the pathogenesis of HBV-related HCC and other liver diseases that affect billions of people worldwide.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Hepatite B , Neoplasias Hepáticas , Masculino , Humanos , Feminino , Vírus da Hepatite B/genética , Neoplasias Hepáticas/patologia , Multiômica , Hepatite B/complicações , Hepatite B/genética , Hepatite B/patologia , Integração Viral
3.
Environ Res ; 220: 115224, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36626948

RESUMO

A storm-drain inlet is an important link in the transport of microplastic pollutants in urban rainwater runoff. In three functional districts (agricultural, commercial, and residential) from Beijing South 2nd Ring Road to South 6th Ring Road, microplastics in storm-drain inlet sediments were analyzed for abundance and characteristics. The abundance of microplastics in the collected samples ranged from 1121 ± 247 items kg-1 to 7393 ± 491 items kg-1. Among the sample areas, the commercial area had the greatest abundance (11094 items kg-1), while the agricultural area had the lowest (833 items kg-1). The microplastics in the samples were mainly fragments, accounting for 50.4%. Microplastics of less than 1 mm accounted for 74.8%. The color of microplastics was diverse, with colored MPs accounting for 26% and transparent ones for 47.8%. Most of the polymers detected were PET, PS, and PP, which are the most commonly used polymers. Overall, the results provide baseline data on microplastic pollution and its associated risks, in addition to guidelines for controlling runoff pollution.


Assuntos
Microplásticos , Poluentes Químicos da Água , Plásticos , Pequim , Baías , Sedimentos Geológicos , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Demografia
4.
J Sep Sci ; 46(13): e2300003, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37078121

RESUMO

Fatty acids have multitudinous biological functions and play a crucial role in many biological processes, but due to poor ionization efficiency and lack of appropriate internal standards, the comprehensive quantification of fatty acids by liquid chromatography-tandem mass spectrometry is still challenging. In this study, a new, accurate, and reliable method for quantifying 30 fatty acids in serum using dual derivatization was proposed. Indole-3-acetic acid hydrazide derivants of fatty acids were used as the internal standard and indole-3-carboxylic acid hydrazide derivants of them were used to quantify. The derivatization conditions were systematically optimized and the method validation results showed good linearity with R2  > 0.9942, low detection limit (0.03-0.6 nM), precision (1.6%-9.8% for intra-day and 4.6%-14.1% for inter-day), recovery (88.2%-107.2% with relative standard deviation < 10.5%), matrix effect (88.3%-105.2% with the relative standard deviation < 9.9%) and stability (3.4%-13.8% for fatty acids derivants in 24 h at 4°C and 4.2%-13.8% for three freeze-thaw cycles). Finally, this method was successfully applied to quantify fatty acids in serum samples of Alzheimer's patients. In contrast to the healthy control group, nine fatty acids showed a significant increase in the Alzheimer's disease group.


Assuntos
Ácidos Graxos , Espectrometria de Massas em Tandem , Humanos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida , Hidrazinas
5.
Bioinformatics ; 37(13): 1821-1827, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-33453108

RESUMO

MOTIVATION: Virus integration in the host genome is frequently reported to be closely associated with many human diseases, and the detection of virus integration is a critically challenging task. However, most existing tools show limited specificity and sensitivity. Therefore, the objective of this study is to develop a method for accurate detection of virus integration into host genomes. RESULTS: Herein, we report a novel method termed HIVID2 that is a significant upgrade of HIVID. HIVID2 performs a paired-end combination (PE-combination) for potentially integrated reads. The resulting sequences are then remapped onto the reference genomes, and both split and discordant chimeric reads are used to identify accurate integration breakpoints with high confidence. HIVID2 represents a great improvement in specificity and sensitivity, and predicts breakpoints closer to the real integrations, compared with existing methods. The advantage of our method was demonstrated using both simulated and real datasets. HIVID2 uncovered novel integration breakpoints in well-known cervical cancer-related genes, including FHIT and LRP1B, which was verified using protein expression data. In addition, HIVID2 allows the user to decide whether to automatically perform advanced analysis using the identified virus integrations. By analyzing the simulated data and real data tests, we demonstrated that HIVID2 is not only more accurate than HIVID but also better than other existing programs with respect to both sensitivity and specificity. We believe that HIVID2 will help in enhancing future research associated with virus integration. AVAILABILITYAND IMPLEMENTATION: HIVID2 can be accessed at https://github.com/zengxi-hada/HIVID2/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

6.
J Nat Prod ; 84(11): 2981-2989, 2021 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-34784203

RESUMO

Arnebinones B, E, and D (1-3) have been found to be sensitive to light, generating complex and diverse proton transfer products when triggered by light. A unique two-step irreversible intramolecular proton transfer of 1 produced five scalemic mixtures, of which four possessed intriguing dual planar chirality. The unprecedented orientation epimerization equilibrium of the intra-annular double bond was first observed and researched in the homologous meroterpenoids by HPLC monitoring and DFT calculations. A "p-benzoquinone-CH2/CH-π" moiety in the structure was the common key feature for the occurrence of this type of photoenolization reaction. The product transformation processes and universality of this photoinduced irreversible proton transfer reaction were analyzed together with the cytotoxic activities of arnebinones B, D, and E, and their photoreaction products.


Assuntos
Benzoquinonas/química , Naftoquinonas/química , Linhagem Celular Tumoral , Humanos , Isomerismo , Naftoquinonas/farmacologia , Fotoquímica , Prótons
7.
J Hepatol ; 70(5): 904-917, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30654066

RESUMO

BACKGROUND & AIMS: Genetic variability in the hepatitis B virus X gene (HBx) is frequently observed and is associated with hepatocellular carcinoma (HCC) progression. However, a genotype classification based on the full-length HBx sequence and the impact of genotypes on hepatitis B virus (HBV)-related HCC prognosis remain unclear. We therefore aimed to perform this genotype classification and assess its clinical impact. METHODS: We classified the genotypes of the full-length HBx gene through sequencing and a cluster analysis of HBx DNA from a cohort of patients with HBV-related HCC, which served as the primary cohort (n = 284). Two independent HBV-related HCC cohorts, a validation cohort (n = 171) and a serum cohort (n = 168), were used to verify the results. Protein microarray assay analysis was performed to explore the underlying mechanism. RESULTS: In the primary cohort, the HBx DNA was classified into 3 genotypes: HBx-EHBH1, HBx-EHBH2, and HBx-EHBH3. HBx-EHBH2 (HBx-E2) indicated better recurrence-free survival and overall survival for patients with HCC. HBx-E2 was significantly correlated with the absence of liver cirrhosis, a small tumor size, a solitary tumor, complete encapsulation and Barcelona Clinic Liver Cancer (BCLC) stage A-0 tumors. Additionally, HBx-E2 served as a significant prognostic factor for patients with BCLC stage B HCC after hepatectomy. Mechanistically, HBx-E2 is unable to promote proliferation in HCC cells and normal hepatocytes. It also fails to activate the Janus kinase 1 (JAK1)/signal transducer and activator of transcription 3 (STAT3)/STAT5 pathway. CONCLUSION: Our study identifies a novel HBx genotype that is unable to promote the proliferation of HCC cells and suggests a potential marker to preoperatively predict the prognosis of patients with BCLC stage B, HBV-associated, HCC. LAY SUMMARY: We classified a novel genotype of the full-length hepatitis B virus X gene (HBx), HBx-E2. This genotype was identified in tumor and nontumor tissues from patients with hepatitis B virus-related hepatocellular carcinoma. HBx-E2 could preoperatively predict the prognosis of patients with intermediate stage hepatocellular carcinoma, after resection.


Assuntos
Carcinoma Hepatocelular/genética , Janus Quinase 1/fisiologia , Neoplasias Hepáticas/genética , Fatores de Transcrição STAT/fisiologia , Transativadores/genética , Proteínas Virais Reguladoras e Acessórias/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Linhagem Celular Tumoral , Genótipo , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Estadiamento de Neoplasias , Prognóstico , Transdução de Sinais/fisiologia , Transativadores/sangue , Transativadores/classificação , Proteínas Virais Reguladoras e Acessórias/sangue , Proteínas Virais Reguladoras e Acessórias/classificação
8.
Biochem Biophys Res Commun ; 516(2): 591-598, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31239154

RESUMO

In the fumarylacetoacetate hydrolase deficient (Fah-/-) mouse, massive liver repopulation can be easily obtained after transplanted hepatocytes. Understanding the mechanisms of complete liver repopulation in Fah-/- mice will be useful for future clinical application. Here, we found that the endogenous hepatocytes in liver of Fah-/- mice undertook senescence during the time of tyrosinemia symptoms. Increase of senescent hepatocytes in Fah-/- mice provided proliferative advantage to the transplanted hepatocytes. Importantly, senescent hepatocytes upregulated the expression of extracellular matrix enzyme, contributing to degradation of extracellular matrix components and weakness of cell adhesion and connection. The liver exhibiting a loose architecture provided the space for the engraftment and expansion of transplanted hepatocytes. These findings underscore the underlying mechanisms of completed liver repopulation in Fah-/- mice. Senescence followed by loose hepatic parenchyma is a preconditioning for liver repopulation, which would be a promising strategy to achieve therapeutic liver repopulation in clinical settings.


Assuntos
Senescência Celular , Hepatócitos/citologia , Fígado/citologia , Animais , Pontos de Checagem do Ciclo Celular , Proliferação de Células , Cicloexanonas , Hepatócitos/transplante , Hidrolases/deficiência , Hidrolases/metabolismo , Camundongos , Nitrobenzoatos
9.
Ann Surg ; 268(6): 943-954, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29521740

RESUMO

BACKGROUND: Despite antiviral treatment has been shown to reduce hepatocellular carcinoma (HCC) recurrence after curative treatment for hepatitis B virus (HBV)-related HCC in patients with high preoperative HBV-DNA levels, it is still unclear whether antiviral therapy is useful in reducing recurrence in patients with low preoperative HBV-DNA levels. METHODS: In this randomized controlled trial, 200 patients who underwent curative resection for HCC with low baseline HBV-DNA levels were randomly assigned to receive preemptive antiviral therapy or not. The primary endpoints were recurrence-free survival. This study was censored on March 31, 2015 when all surviving patients had a minimum follow-up of 60 months. The analysis was done on an intention-to-treat basis. RESULTS: The baseline clinical, laboratory, and tumor characteristics of the 2 groups were comparable. The 1-, 3-, and 5-year recurrence-free survival rates for the antiviral group and the control group were 85.9%, 55.2%, and 52.0% and 80.6%, 40.9%, and 32.3%, respectively. The corresponding overall survival rates for the 2 groups were 94.0%, 75.7%, and 64.1% and 90.0%, 62.4%, and 43.7%, respectively. The recurrence-free survival and overall survival for the antiviral group were significantly better than the control group (P = 0.016, P = 0.004, respectively). After adjusting for confounding prognostic factors in a Cox model, the relative risks of recurrence and death for antiviral treatment were 0.601 [95% confidence interval (CI), 0.409-0.884; P = 0.010] and 0.509 (95% CI, 0.333-0.778; P = 0.002), respectively. Antiviral therapy was an independent protective factor of late tumor recurrence (hazard ratio [HR] = 0.316, 95% CI 0.157-0.637; P = 0.001) but not of early tumor recurrence (HR = 0.782, 95% CI, 0.493-1.240; P = 0.296). CONCLUSIONS: In patients with low preoperative HBV-DNA levels, antiviral therapy significantly reduced HCC recurrence after R0 hepatic resection.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/virologia , DNA Viral/sangue , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/virologia , Recidiva Local de Neoplasia/prevenção & controle , Telbivudina/uso terapêutico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Feminino , Vírus da Hepatite B/genética , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de Sobrevida
10.
Hepatology ; 65(5): 1628-1644, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28027570

RESUMO

Potential biomarkers that can be used to determine prognosis and perform targeted therapies are urgently needed to treat patients with hepatocellular carcinoma (HCC). To meet this need, we performed a screen to identify functional genes associated with hepatocellular carcinogenesis and its progression at the transcriptome and proteome levels. We identified aldehyde dedydrogenase-2 (ALDH2) as a gene of interest for further study. ALDH2 levels were significantly lower at the mRNA and protein level in tumor tissues than in normal tissues, and they were even lower in tissues that exhibited increased migratory capacity. A study of clinical associations showed that ALDH2 is correlated with survival and multiple migration-associated clinicopathological traits, including the presence of metastasis and portal vein tumor thrombus. The result of overexpressing or knocking down ALDH2 showed that this gene inhibited migration and invasion both in vivo and in vitro. We also found that ALDH2 altered the redox status of cells by regulating acetaldehyde levels and that it further activated the AMP-activated protein kinase (AMPK) signaling pathway. CONCLUSION: Decreased levels of ALDH2 may indicate a poor prognosis in HCC patients, while forcing the expression of ALDH2 in HCC cells inhibited their aggressive behavior in vitro and in mice largely by modulating the activity of the ALDH2-acetaldehyde-redox-AMPK axis. Therefore, identifying ALDH2 expression levels in HCC might be a useful strategy for classifying HCC patients and for developing potential therapeutic strategies that specifically target metastatic HCC. (Hepatology 2017;65:1628-1644).


Assuntos
Aldeído-Desidrogenase Mitocondrial/metabolismo , Carcinoma Hepatocelular/enzimologia , Neoplasias Hepáticas Experimentais/enzimologia , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , China/epidemiologia , Expressão Ectópica do Gene , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Fígado/patologia , Neoplasias Hepáticas Experimentais/mortalidade , Neoplasias Hepáticas Experimentais/patologia , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Metástase Neoplásica , Oxirredução , Distribuição Aleatória
11.
Hepatology ; 63(4): 1272-86, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26698170

RESUMO

UNLABELLED: Solid tumors often suffer from suboptimal oxygen and nutrient supplies. This stress underlies the requirement for metabolic adaptation. Aberrantly activated de novo lipogenesis is critical for development and progression of human hepatocellular carcinoma (HCC). However, whether de novo lipogenesis influences biological behaviors of HCCs under conditions of metabolic stress are still poorly understood. Here, we show that HCCs display distinct levels of glucose-derived de novo lipogenesis, which are positively correlated with their survival responses to glucose limitation. The enhanced lipogenesis in HCCs is characterized by an increased expression of rate-limiting enzyme acetyl-coenzyme A carboxylase alpha (ACCα). ACCα-mediated fatty acid (FA) synthesis determines the intracellular lipid content that is required to maintain energy hemostasis and inhibit cell death by means of FA oxidation (FAO) during metabolic stress. In accord, overexpression of ACCα facilitates tumor growth. ACCα forms a complex with carnitine palmitoyltransferase 1A (CPT1A) and prevents its mitochondria distribution under nutrient-sufficient conditions. During metabolic stress, phosphorylation of ACCα leads to dissociation of the complex and mitochondria localization of CPT1A, thus promoting FAO-mediated cell survival. Therefore, ACCα could provide both the substrate and enzyme storage for FAO during glucose deficiency. Up-regulation of ACCα is also significantly correlated with poorer overall survival and disease recurrence postsurgery. Multivariate Cox's regression analysis identified ACCα as an effective predictor of poor prognosis. CONCLUSION: These results present novel mechanistic insight into a pivotal role of ACCα in maintaining HCC survival under metabolic stress. It could be exploited as a novel diagnostic marker and therapeutic target.


Assuntos
Acetil-CoA Carboxilase/metabolismo , Carcinoma Hepatocelular/enzimologia , Glucose/metabolismo , Neoplasias Hepáticas/enzimologia , Estresse Oxidativo , Acetil-CoA Carboxilase/genética , Animais , Apoptose/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Modelos Animais de Doenças , Ácido Graxo Sintases/metabolismo , Ácidos Graxos/metabolismo , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Xenoenxertos , Humanos , Estimativa de Kaplan-Meier , Metabolismo dos Lipídeos/fisiologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Camundongos , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Análise de Sobrevida , Regulação para Cima
12.
Mol Carcinog ; 54(12): 1584-95, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25307746

RESUMO

Pioglitazone (PGZ), a synthetic PPARγ ligand, is known to have anti-tumor activity. However, it is unclear how it acts against hepatocellular carcinoma (HCC). We hypothesized that the pathological receptor for advanced glycation end products (RAGE) is involved in the PGZ anti-tumor process. To test this notion, human primary HCC tissues and corresponding adjacent non-cancerous tissues (ANCT) from 75 consecutive cases were analyzed. The expression and clinical significance of RAGE was assessed by immunohistochemical assay through tissue microarray. After HCC cells were pretreated with different concentrations of PGZ, cell proliferation, apoptosis, cell invasion, and cell cycle distribution were evaluated by multiple assays. The results showed that, the positive expression of RAGE was significantly higher in HCC tissues than in ANCT (66.7% vs. 36.0%, P < 0.001), and was closely associated with pathological staging (P = 0.014) and lymph-vascular space invasion (P = 0.003). Moreover, PGZ inhibited proliferative activity and invasive potential, and induced apoptosis and cell cycle arrest in HCC cells resulting in increased expression of PPARγ and decreased expression of RAGE, NF-κB, HMGB1, p38MAPK, Ki-67, MMP-2, and CyclinD1. Furthermore, knockdown of RAGE or NF-κB by siRNA effectively suppressed cell proliferation and invasion, and mediated the inhibitory effects of PGZ in HCC cells. Taken together, our findings suggest that, RAGE is overexpressed in human HCC tissues, and is closely associated with the pathological staging and tumor invasion of HCC. In addition, PGZ as a PPARγ agonist may inhibit growth and invasion of HCC cells via blockade of the RAGE signaling.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Invasividade Neoplásica/prevenção & controle , PPAR gama/agonistas , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidores , Tiazolidinedionas/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Pioglitazona , Transdução de Sinais/efeitos dos fármacos
13.
Mol Pharm ; 12(2): 644-52, 2015 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-25495890

RESUMO

Targeted delivery system would be an interesting platform to enhance the therapeutic effect and to reduce the side effects of anticancer drugs. In this study, we have developed lactobionic acid (LA)-modified chitosan-stearic acid (CS-SA) (CSS-LA) to deliver doxorubicin (DOX) to hepatic cancer cells. The average particle size of CSS-LA/DOX was ∼100 nm with a high entrapment efficiency of >95%. Drug release studies showed that DOX release from pH-sensitive micelles is significantly faster at pH 5.0 than at pH 7.4. The LA conjugated micelles showed enhanced cellular uptake in HepG2 and BEL-7402 liver cancer cells than free drug and unconjugated micelles. Consistently, CSS-LA/DOX showed enhanced cell cytotoxicity in these two cell lines. Annexin-V/FITC and PI based apoptosis assay showed that the number of living cells greatly reduced in this group with marked presence of necrotic and apoptotic cells. LA-conjugated carrier induced typical chromatic condensation of cells; membrane blebbing and apoptotic bodies began to appear. In vivo, CSS-LA/DOX showed an excellent tumor regression profile with no toxic side effects. The active targeting moiety, long circulation profile, and EPR effect contributed to its superior anticancer effect in HepG2 based tumor. Our results showed that polymeric micelles conjugated with LA increased the therapeutic availability of DOX in the liver cancer cell based solid tumor without any toxic side effects. The active targeting ligand conjugated nanoparticulate system could be a promising therapeutic strategy in the treatment of hepatic cancers.


Assuntos
Quitosana/química , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Neoplasias Hepáticas/tratamento farmacológico , Micelas , Polímeros/química , Ácidos Esteáricos/química , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Dissacarídeos/química , Doxorrubicina/química , Sistemas de Liberação de Medicamentos/métodos , Células Hep G2 , Humanos , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(2): 512-8, 2015 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-25970923

RESUMO

Matrix effect between reference materials and samples is one of the major factors affecting the accuracy of analytical results by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). However, there is no method or calculation formula to quantify matrix effect between standards and samples up to date. In this paper, the linear correlation coefficient r of the Ii/I(is-Ci)/Cis graphs of element pairs were used to characterize the matrix effect, which took the ratios of concentrations (ci/ c(is)) and intensities (Ii/Iis) of the analytical element and internal standard element as x-axis and gamma-axis, respectively. Matrix effects of 6 element pairs in 13 glass reference materials, 2 sulfide reference materials and 2 sulfide minerals using Fe as internal standard was studied, with the linear correlation coefficient r of Fe-Cu, Fe-Zn element pairs both less than 0. 999 and trace Fe--Mn, Fe--Co, Fe--Ga, Fe--Pb element pairs all better than 0.999. Matrix effects of 3 major element pairs in 2 sulfide ref- erence materials and 6 sulfide minerals using S as internal standard was also studied, with the linear correlation coefficient r of S--Fe, S--Cu, S--Zn all less than 0.999. The great majority of relative errors of EMPA analytical results for major elements in sulfide minerals were greater than 10%, whether analyzed using Fe as internal standard with glass reference materials as external standard, or S as internal standard with sulfide reference materials MASS-1, IMER-1 as external standard, respectively. But the most analytical results for trace elements calibrated by glass reference materials using Fe as internal standard were well agreed with sulfide standard MASS-1, with the relative errors less than 15%. The results showed that matrix effects existed in glass reference materials, sulfide reference materials and sulfide minerals, and it also proved a certain rationality and practicability for quantification of matrix effect using the linear correlation coefficient r of the Ii/Iis-Ci/Cis graphs by this element pair method. This study also indicated that trace elements in sulfide minerals could be calibrated using Fe as internal standard with non-matrix matched glass reference materials as external standard, especially for NIST610 contained nearly all the trace elements in sulfide minerals and with relative high concentrations of each element, which obtained analytical results agreed well with sulfide standard MASS-1.

15.
Biomed Mater ; 19(4)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38857606

RESUMO

Chemotherapeutic agents hold significant clinical potential in combating tumors. However, delivering these drugs to the tumor site for controlled release remains a crucial challenge. In this study, we synthesize and construct a glutathione (GSH) and acid dual-responsive bismuth-based nano-delivery platform (BOD), aiming for sonodynamic enhancement of docetaxel (DTX)-mediated tumor therapy. The bismuth nanomaterial can generate multiple reactive oxygen species under ultrasound stimulation. Furthermore, the loading of DTX to form BOD effectively reduces the toxicity of DTX in the bloodstream, ensuring its cytotoxic effect is predominantly exerted at the tumor site. DTX can be well released in high expression of GSH and acidic tumor microenvironment. Meanwhile, ultrasound can also promote the release of DTX. Results from bothin vitroandin vivoexperiments substantiate that the synergistic therapy involving chemotherapy and sonodynamic therapy significantly inhibits the growth and proliferation of tumor cells. This study provides a favorable paradigm for developing a synergistic tumor treatment platform for tumor microenvironment response and ultrasound-promoted drug release.


Assuntos
Antineoplásicos , Bismuto , Docetaxel , Glutationa , Microambiente Tumoral , Terapia por Ultrassom , Bismuto/química , Animais , Glutationa/metabolismo , Docetaxel/farmacologia , Docetaxel/química , Camundongos , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Terapia por Ultrassom/métodos , Espécies Reativas de Oxigênio/metabolismo , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Camundongos Endogâmicos BALB C , Liberação Controlada de Fármacos , Nanopartículas/química , Feminino
16.
J Chromatogr A ; 1730: 465122, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-38941796

RESUMO

In the realm of electrospray ionization mass spectrometry (ESI-MS), distinguishing among isomers poses a significant challenge due to the minimal spectral differences that often arise from their subtle structural differences. This makes the accurate identification of these compounds through solely experimental spectra a daunting task. Computational chemistry has emerged as a pivotal tool in bridging the gap between experimental observations and theoretical understanding. This study used the MS fragmentation simulation software, QCxMS, to model the spectra of five groups of isomers, encompassing 11 compounds, found in the traditional Chinese medicine, Zhishi Xiebai Guizhi Decoction. By comparing the spectra predicted through computational methods with those derived from Ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS) experiments, it was observed that, following the optimization of simulation parameters, QCxMS was capable of generating reliable spectra for all examined compounds. Notably, the data calculated under both GFN1-xTB and GFN2-xTB levels exhibited no significant discrepancies. Further analysis enabled the identification of the principal fragments of the 11 compounds from the theoretical data, facilitating the deduction of their fragmentation pathways. The Density Functional Theory (DFT) method was subsequently applied to compute the primary fragmentation energies of these compounds. The findings revealed a congruence between the energy data calculated using both thermodynamic and kinetic approaches and the observed fragment abundance of the isomers. This alignment providing a more precise theoretical framework for understanding the mechanisms underlying the generation of fragment ion differences among isomers.


Assuntos
Teoria da Densidade Funcional , Medicamentos de Ervas Chinesas , Software , Espectrometria de Massas por Ionização por Electrospray , Isomerismo , Medicamentos de Ervas Chinesas/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Cromatografia Líquida de Alta Pressão/métodos , Medicina Tradicional Chinesa
17.
ACS Appl Mater Interfaces ; 16(17): 22147-22154, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38639142

RESUMO

The high performance of a multistage thermoelectric cooler (multi-TEC) used in a wide low-temperature range depends on the optimized thermoelectric (TE) performance of materials during the corresponding working temperature range for each stage. Despite decades of research on the commercial TE materials of Bi2Te3, the main research is still focused on temperatures above 300 K, lacking suitable hierarchical low-temperature n-Bi2Te3 for multistage TEC. In this work, we systematically investigated the influence of doping concentration and matrix material compositions on the TE performance of n-Bi2Te3 below room temperature by the high-energy ball milling and hot deformation. Consequently, two hierarchical n-Bi2Te3 materials with excellent mechanical properties working below 248 and around 298 K, respectively, have been screened out. The Bi2Te2.7Se0.3 + 0.03 wt % TeI4 can be adopted in a low-temperature range that exhibits the high average figure of merit (zTave) of 0.61 within 173-248 K. Meanwhile, the Bi2Te2.7Se0.3 + 0.05 wt % TeI4 sample displays a competitive zTave of 0.85 within 248-298 K, which can be applied above 248 K. The research of hierarchical TE materials provides valuable insights into the high-performance design of multistage TE cooling devices.

18.
Membranes (Basel) ; 14(2)2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38392678

RESUMO

The study objective was to field-validate the technical feasibility of a membrane- and adsorption-enhanced water gas shift reaction process employing a carbon molecular sieve membrane (CMSM)-based membrane reactor (MR) followed by an adsorptive reactor (AR) for pre-combustion CO2 capture. The project was carried out in two different phases. In Phase I, the field-scale experimental MR-AR system was designed and constructed, the membranes, and adsorbents were prepared, and the unit was tested with simulated syngas to validate functionality. In Phase II, the unit was installed at the test site, field-tested using real syngas, and a technoeconomic analysis (TEA) of the technology was completed. All project milestones were met. Specifically, (i) high-performance CMSMs were prepared meeting the target H2 permeance (>1 m3/(m2.hbar) and H2/CO selectivity of >80 at temperatures of up to 300 °C and pressures of up to 25 bar with a <10% performance decline over the testing period; (ii) pelletized adsorbents were prepared for use in relevant conditions (250 °C < T < 450 °C, pressures up to 25 bar) with a working capacity of >2.5 wt.% and an attrition rate of <0.2; (iii) TEA showed that the MR-AR technology met the CO2 capture goals of 95% CO2 purity at a cost of electricity (COE) 30% less than baseline approaches.

19.
Materials (Basel) ; 16(16)2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37629820

RESUMO

Pseudo-ternary half-Heusler thermoelectric materials, which are formed by filling the B sites of traditional ternary half-Heusler thermoelectric materials of ABX with equal atomic proportions of various elements, have attracted more and more attention due to their lower intrinsic lattice thermal conductivity. High-purity and relatively dense Ti1-xNbx(FeCoNi)Sb (x = 0, 0.01, 0.03, 0.05, 0.07 and 0.1) alloys were prepared via microwave synthesis combined with rapid hot-pressing sintering, and their thermoelectric properties are investigated in this work. The Seebeck coefficient was markedly increased via Nb substitution at Ti sites, which resulted in the optimized power factor of 1.45 µWcm-1K-2 for n-type Ti0.93Nb0.07(FeCoNi)Sb at 750 K. In addition, the lattice thermal conductivity was largely decreased due to the increase in phonon scattering caused by point defects, mass fluctuation and strain fluctuation introduced by Nb-doping. At 750 K, the lattice thermal conductivity of Ti0.97Nb0.03(FeCoNi)Sb is 2.37 Wm-1K-1, which is 55% and 23% lower than that of TiCoSb and Ti(FeCoNi)Sb, respectively. Compared with TiCoSb, the ZT of the Ti1-xNbx(FeCoNi)Sb samples were significantly increased. The average ZT values of the Nb-doped pseudo-ternary half-Heusler samples were dozens of times that of the TiCoSb prepared using the same process.

20.
Adv Healthc Mater ; 12(21): e2300089, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37055912

RESUMO

Hypoxia is a typical feature of most solid tumors and has important effects on tumor cells' proliferation, invasion, and metastasis. This is the key factor that leads to poor efficacy of different kinds of therapy including chemotherapy, radiotherapy, photodynamic therapy, etc. In recent years, the construction of hypoxia-relieving functional nanoplatforms through nanotechnology has become a new strategy to reverse the current situation of tumor microenvironment hypoxia and improve the effectiveness of tumor treatment. Here, the main strategies and recent progress in constructing nanoplatforms are focused on to directly carry oxygen, generate oxygen in situ, inhibit mitochondrial respiration, and enhance blood perfusion to alleviate tumor hypoxia. The advantages and disadvantages of these nanoplatforms are compared. Meanwhile, nanoplatforms based on organic and inorganic substances are also summarized and classified. Through the comprehensive overview, it is hoped that the summary of these nanoplatforms for alleviating hypoxia could provide new enlightenment and prospects for the construction of nanomaterials in this field.


Assuntos
Neoplasias , Fotoquimioterapia , Humanos , Hipóxia Tumoral , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Oxigênio , Hipóxia/tratamento farmacológico , Microambiente Tumoral , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/farmacologia
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa