RESUMO
Doxorubicin (DOX) is a powerful anthracycline antineoplastic drug used to treat a wide spectrum of tumors. However, its clinical application is limited due to cardiotoxic side effects. Astragaloside IV (AS IV), one of the major compounds present in aqueous extracts of Astragalus membranaceus, possesses potent cardiovascular protective properties, but the underlying molecular mechanisms are unclear. Thus, the aim of this study was to investigate the effect of AS IV on DOX-induced cardiotoxicity (DIC). Our findings revealed that DOX induced pyroptosis through the caspase-1/gasdermin D (GSDMD) and caspase-3/gasdermin E (GSDME) pathways. AS IV treatment significantly improved the cardiac function and alleviated myocardial injury in DOX-exposed mice by regulating intestinal flora and inhibiting pyroptosis; markedly suppressed the levels of cleaved caspase-1, N-GSDMD, cleaved caspase-3, and N-GSDME; and reversed DOX-induced downregulation of silent information regulator 1 (SIRT1) and activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome in mice. The SIRT1 inhibitor EX527 significantly blocked the protective effects of AS IV. Collectively, our results suggest that AS IV protects against DIC by inhibiting pyroptosis through the SIRT1/NLRP3 pathway.
Assuntos
Miócitos Cardíacos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Saponinas , Triterpenos , Camundongos , Animais , Miócitos Cardíacos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose/fisiologia , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/etiologia , Cardiotoxicidade/metabolismo , Caspase 3/metabolismo , Sirtuína 1/metabolismo , Gasderminas , Doxorrubicina/efeitos adversos , Caspase 1/metabolismoRESUMO
Emergent quantum phenomena in two-dimensional van der Waal (vdW) magnets are largely governed by the interplay between exchange and Coulomb interactions. The ability to precisely tune the Coulomb interaction enables the control of spin-correlated flat-band states, band gap, and unconventional magnetism in such strongly correlated materials. Here, we demonstrate a gate-tunable renormalization of spin-correlated flat-band states and bandgap in magnetic chromium tribromide (CrBr3) monolayers grown on graphene. Our gate-dependent scanning tunneling spectroscopy (STS) studies reveal that the interflat-band spacing and bandgap of CrBr3 can be continuously tuned by 120 and 240 meV, respectively, via electrostatic injection of carriers into the hybrid CrBr3/graphene system. This can be attributed to the self-screening of CrBr3 arising from the gate-induced carriers injected into CrBr3, which dominates over the weakened remote screening of the graphene substrate due to the decreased carrier density in graphene. Precise tuning of the spin-correlated flat-band states and bandgap in 2D magnets via electrostatic modulation of Coulomb interactions not only provides effective strategies for optimizing the spin transport channels but also may exert a crucial influence on the exchange energy and spin-wave gap, which could raise the critical temperature for magnetic order.
RESUMO
Significant breakthroughs have been made in the development of surface-enhanced Raman scattering (SERS) substrates constructed by depositing plasmonic Ag onto nanostructured platforms. AlOOH is widely fabricated using hydrothermal, microwave, and microemulsion methods. Among these, the high catalytic activity of AlOOH prepared by the microemulsion method is derived from its high specific surface area, more active surface OH groups, and multi-active adsorption sites. And nanomaterials with such excellent properties have not yet been fabricated on a SERS-based platform to improve the Raman-enhanced properties of Ag achieving high-sensitivity detection of probe molecules especially with affinity for OH groups. The precious metal Ag has long been known to serve as traps to capture electrons and holes generated by plasmon resonance, reducing electron-hole recombination and exhibiting high activity in photocatalytic processes. In this work, to demonstrate the SERS substrate activity of the AlOOH@Ag complex, it has been successfully applied to identify congo red (CR) molecules with high sensitivity, methyl blue (MB) and methyl orange (MO), enabling trace-level detection with enhanced performance much stronger than Ag substrate.
Assuntos
Nanopartículas Metálicas , Prata , Hidróxido de Alumínio , Óxido de Alumínio , Nanopartículas Metálicas/química , Prata/química , Análise Espectral Raman/métodosRESUMO
Sericin, an industrial waste of the silk industry, is a promising precursor for adsorbent preparation. In this work, an efficient and novel sericin-derived carbon aerogel (SCA) was used to improve the adsorption efficiency of oils and organic solvents. The SCA demonstrated a high-efficiency sorption capacity of not only soybean oil (adsorption capacity reached up to 167.69 times its weight) but also chloroform and methylene chloride (adsorption capacity of 193.67 g/g and 173.25 g/g respectively). It is observed that SCA could be regenerated multiple times through combustion and after five cycles, its adsorbability to ethanol, dimethyl sulfoxide, and soybean oil remained high at 59.08 g/g, 59.34 g/g, and 137.36 g/g, respectively. The physical and chemical characteristics of sericin and SCA were analyzed using Scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET), X-ray diffraction (XRD), Raman spectra and Fourier transform infrared spectroscopy (FTIR) analysis. The results suggest that SCA is an adsorbent with excellent properties and can significantly increase the adsorption capacity of oils and organic solvents. The overall results indicate that SCA is effectively used as an adsorbent for the adsorption of oils and organic solvents, which will contribute to reduce the discharge of sericin-containing wastewater and alleviate pollution caused by oil and organic solvent leakage.
Assuntos
Sericinas , Poluentes Químicos da Água , Adsorção , Carbono , Óleos , Solventes , Óleo de Soja/análise , Espectroscopia de Infravermelho com Transformada de Fourier , Poluentes Químicos da Água/análiseRESUMO
ETHNIC PHARMACOLOGICAL RELEVANCE: Plant materials are used as complementary and alternative therapies all over the world for the treatment of various diseases. Ulcerative colitis (UC), a chronic nonspecific inflammatory bowel disease listed as one of the modern refractory diseases by the World Health Organization, has a long course, is challenging to cure, and is prone to cause cancer. Recent years have witnessed a growing trend of applying traditional Chinese medicine (TCM) to UC. AIM OF THIS REVIEW: This review presents an overview of the pathogenesis of UC and reports the therapeutic effect of TCM on UC (including TCM prescriptions, single TCM, and treatments using TCM ingredients) to provide a theoretical basis for the use of TCM in treating UC. METHODS: We performed a collection and collation of relevant scientific articles from different scientific databases regarding TCM and its usefulness in treating UC. In this paper, the therapeutic effect of TCM is summarized and analyzed according to the existing experimental and clinical research. RESULTS: There are positive signs that TCM primarily regulates inflammatory cytokines, intestinal flora, and the immune system, and also protects the intestinal mucosa. Hence, it can play a role in treating UC. CONCLUSION: TCM has a definite curative effect in the treatment of UC. It can alleviate and treat UC in a variety of ways. We should take syndrome differentiation and treatment differentiation as the basis. With the help of modern medicine, TCM's clinical curative effects can be enhanced for the treatment of UC.
Assuntos
Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa/métodos , Animais , Citocinas/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Mucosa Intestinal/efeitos dos fármacosRESUMO
Although selenium (Se) is an essential microelement for humans and animals, it is a potentially toxic element due to its bioaccumulation potential. In this study, Se fertilizer was supplied in a greenhouse vegetable (cucumber) plantation using an innovative system consisting of nanobubbles (NB_Se) and compared to that under conventional conditions of fertigation (C_Se) with six doses. The results revealed that NB_Se significantly reduced soil Se accumulation (38%-144%) and increased cucumber Se content compared with the C_Se treatments at the same Se dose. NB_Se significantly lowered the soil bacterial diversity, with an initial increase and then decrease with the Se doses. Bacterial associations and potential keystone taxa also differed between the NB_Se and C_Se. The greater abundance of oxidizing bacteria (indicated by the function composition of bacterial community) and the improved soil redox environment created by NBs sustained more available Se for plants, leading to a reduction in soil Se residual and an increase in the plant Se content. Our results highlight the feasibility and efficiency of NB_Se and demonstrate the important implications of Se for the maintenance of soil health and sustainability.
Assuntos
Cucumis sativus , Selênio , Animais , Bactérias/genética , Fertilizantes/análise , Humanos , SoloRESUMO
BACKGROUND: Shikonin (SKN), a naturally occurring naphthoquinone, is a major active chemical component isolated from Lithospermum erythrorhizon Sieb Zucc, Arnebia euchroma (Royle) Johnst, or Arnebia guttata Bunge, and commonly used to treat viral infection, inflammation, and cancer. However, its underlying mechanism has not been elucidated. OBJECTIVE: This study aims to explore the antitumor mechanism of SKN in colorectal cancer (CRC) through network pharmacology and cell experiments. METHODS: SymMap database and Genecards were used to predict the potential targets of SKN and CRC, while the cotargets were obtained by Venn diagram. The cotargets were imported into the website of String and DAVID, constructing the protein-protein interaction (PPI) network, performing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, the Compound-Target-Pathway (C-T-P) network was generated by connecting potential pathways with the corresponding targets. RESULTS: According to the results of network pharmacological analysis, the cell experiments were used to verify the key signal pathway. The most relevant target of SKN for the treatment of CRC was PI3K/Akt signaling pathway. SKN inhibited CRC cells (HT29 and HCT116) proliferation, migration, and invasion, and promoted cell apoptosis by targeting IL6 and inhibiting the IL6R/PI3K/Akt signaling pathway. SKN promotes apoptosis and suppresses CRC cells' (HT29 and HCT116) activity through the PI3K-Akt signaling pathway. CONCLUSION: This research not only provided a theoretical and experimental basis for more in- -depth studies but also offered an efficient method for the rational utilization of a series of Traditional Chinese medicines as anti-CRC drugs.
Assuntos
Neoplasias Colorretais , Medicamentos de Ervas Chinesas , Naftoquinonas , Neoplasias Colorretais/patologia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Simulação de Acoplamento Molecular , Naftoquinonas/farmacologia , Naftoquinonas/uso terapêutico , Farmacologia em Rede , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
BACKGROUND: Literature has demonstrated that diabetes is associated with renal complication and testicular dysfunctions. The current study explored the potential of Tiliacora triandra extract and its major component against diabetic kidney and testicular damages in rats. METHODS: Diabetes was induced by high fat diet/streptozotocin (HFD/STZ) and treated orally with Tiliacora triandra extract (TTE, 100 and 400 mg kg-1 body weight) and its major component, 5,7-dihydroxy-6-oxoheptadecanoic acid (DHA, 25 mg kg-1 body weight) for 30 consecutive days. Testicular activities of testicular enzymes, serum levels of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), sperm parameters and urinalysis for protein and albumin levels were evaluated. Renal and testicular biomarkers of oxidative stress and pro-inflammation were analysed along with histology. RESULTS: The experimental diabetes induced significant alterations in the levels and activities of indices evaluated compared to non-diabetic normal rats. The 28-day treatment of diabetic rats with TTE and DHA markedly improved activities of testicular enzymes, restored levels of testosterone, LH and FSH and sperm parameters compared to untreated diabetic rats. TTE and DHA abrogated proteinuria and reversed urine albumin level. Testicular and renal oxidative stress and pro-inflammation were attenuated in diabetic rats treated with TTE and DHA. The diabetes-mediated histopathological damage was alleviated in the kidney and testis. CONCLUSION: The protective effect of TTE and DHA against diabetes induced kidney and testicular damages may be related to its antioxidant and anti-inflammatory activities. © 2020 Society of Chemical Industry.
Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Menispermaceae/química , Extratos Vegetais/administração & dosagem , Testículo/efeitos dos fármacos , Animais , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/imunologia , Hormônio Foliculoestimulante/sangue , Humanos , Rim/efeitos dos fármacos , Rim/imunologia , Rim/metabolismo , Hormônio Luteinizante/sangue , Masculino , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley , Testículo/fisiopatologia , Testosterona/sangueRESUMO
Paeonia ostii is now being extensively planted for oil extraction in China, which is recognized as a single oil-use tree peony cultivar and commonly called 'Fengdan'. This study investigated the effects of nitrogen fertilizer on oil yield, fatty acid compositions and antioxidant activity of P. ostii. Oil yield (33.46 %), oleic acid (25.12 %), linoleic acid (29.21 %) and α-linolenic acid (43.12 %) reached the maximum at N450 treatment, with significant differences compared with other treatments (P<0.05). Furthermore, strong antioxidant activity with low DPPHIC50 value (19.43±1.91â µg mL-1 ) and large ABTS value (1216.53±30.21â µmol Trolox g-1 ) and FRAP value (473.57±9.11â µmol Trolox g-1 ) was also observed at N450. Palmitic acid (5.57 %) and stearic acid (2.02 %) reached a maximum at N375, but not significant with N450 (P<0.05). Nitrogen fertilizer could promote oil yield, fatty acid accumulation and antioxidant activity, and N450 (450â kg ha-1 ) is recommended as the optimum application for P. ostii.
Assuntos
Antioxidantes/farmacologia , Ácidos Graxos/análise , Fertilizantes , Nitrogênio/administração & dosagem , Paeonia/química , Extratos Vegetais/farmacologia , Cromatografia Gasosa-Espectrometria de Massas/métodos , Paeonia/crescimento & desenvolvimento , Extratos Vegetais/química , Óleos de Plantas/análiseRESUMO
OBJECTIVE: To compare the efficacy between acupoint selection of meridian diagnosis and regular acupoint selection for chronic atrophic gastritis (CAG). METHODS: A total of 70 cases of CAG were randomly divided into an observation group (35 cases, 5 cases dropped off) and a control group (35 cases, 5 dropped off). In the observation group, according to the hand diagnosis of meridians and the results of 80-channels energy determinator, based on the principle of child-mother relation acupoint combination, the luo-connecting point and back-shu points were added for excess syndrome, and the yuan-primary point, front-mu points and he-sea point of foot meridians were added for deficiency syndrome; in addition, the acupoints of the eight extraordinary meridians were added based on the nature of acupoints. In the control group, Zhongwan (CV 12), Neiguan (PC 6), Zusanli (ST 36) and Gongsun (SP 4) were selected as the primary acupoints, and additional acupoints were added according to syndrome differentiation. The two groups were treated twice a week (Tuesday and Thursday, respectively), totally for 6 months. Six months after treatment, the follow-up was conducted. The clinical symptom score, gastroenteropathy patient reported outcomes (PRO) scale score before treatment, after treatment and during follow-up as well as the score of pathological changes of gastric mucosa before and after treatment were compared between the two groups. RESULTS: After treatment and during follow-up, the clinical symptom scores and gastroenteropathy PRO scale scores were decreased in the two groups (P<0.01, P<0.001); at the follow-up, the gastroenteropathy PRO scale score in the observation group was lower than that in the control group (P<0.01). After treatment, the scores of pathological changes of gastric mucosa in the two groups were decreased (P<0.01), and the score in the observation group was lower than that in the control group (P<0.05). CONCLUSION: The acupoint selection of meridian diagnosis is superior to regular acupoint selection for CAG, which has better efficacy, more significant improvement on gastric mucosa pathology, and more stable long-term effect.
Assuntos
Terapia por Acupuntura , Gastrite Atrófica , Meridianos , Pontos de Acupuntura , Gastrite Atrófica/diagnóstico , Gastrite Atrófica/terapia , Humanos , SíndromeRESUMO
As a new woody oleaginous crop, tree peony is now being widely developed and utilized, which attributed to the outstanding oil-use features regarding the fatty acid profiles and bioactivity. The major fatty acid profiles and bioactivity of seed oils in ten tree peony varieties collected from a common garden were investigated in the present study. The results showed that the oil yields, fatty acid profiles, bioactivity of seed oils existed significant variations among ten tree peony varieties (P<0.05). Considered the application value, 'Fengdan' (FD) and 'Ziban' (ZB) was the optimal resources as the high oil yields, rich unsaturated fatty acids especially high α-linolenic acid of 40.46 %, great antioxidant activity with low IC50 values, high ABTS and FRAP values, and strong antimicrobial activity with high DIZ and low MIC/MBC values. The study also confirmed seed oil of tree peony as the potential raw materials sources in functional food, pharmaceuticals and cosmetics for human health.
Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antioxidantes/farmacologia , Cosméticos/química , Ácidos Graxos/farmacologia , Paeonia/química , Antibacterianos/química , Antifúngicos/química , Antioxidantes/química , Bactérias/efeitos dos fármacos , Benzotiazóis/antagonistas & inibidores , Ácidos Graxos/química , Recuperação de Fluorescência Após Fotodegradação , Fungos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Óleos de Plantas/química , Sementes/química , Ácidos Sulfônicos/antagonistas & inibidores , Árvores/químicaRESUMO
The application of immunological checkpoint inhibitors (ICIs) has modified many treatment strategies of malignant tumors, which has become a milestone in cancer therapy. The principle of action can be explained as "brake theory". After releasing the brakes by ICIs, unprecedented systemic toxicities, even some refractory and fatal immune-related adverse effects (irAEs) may develop. In this article, we summarized the recommended treatments of grade 3-4 severe irAEs in the latest European Society for Medical Oncology (ESMO), National Comprehensive Cancer Network (NCCN)/American Society of Clinical Oncology (ASCO), Society for Immunotherapy of Cancer (SITC) and Chinese Society of Clinical Oncology (CSCO) guidelines and consensus. We also performed a systemic review of case reports and reviews of irAEs up to May 20, 2019 in PubMed and Chinese journals. Successful applications of specific immunosuppressive drugs and stimulating factors beyond the above guidelines and consensus were supplemented and highlighted, including agents blocking interleukin 6 (IL-6), rituximab, anti-tumor necrosis factor-α (TNFα) monoclonal antibody (mAb), anti-integrin 4 mAb, Janus kinase inhibitors, thrombopoietin receptor agonists and antithymocyte globulin (ATG) etc. We put some concerns of using high-dose steroids for long-term, and emphasize the secondary infections, tumor progression, and unavailability of ICI re-challenge during steroid treatment. We propose the "De-escalation Therapy" principle for severe and refractory irAEs, and suggest that immunosuppressive drugs specifically targeting cytokines should be used as early as possible. Many irAEs in the era of immunotherapy are unprecedented compared with traditional chemotherapy and small-molecule targeted therapy, which is a big challenge to oncologists. Therefore, the establishment of multidisciplinary system is very important for the management of cancer patients.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/terapia , Imunoterapia/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/imunologiaRESUMO
Cysteine oxygenase (CDO) is a mononuclear nonhemoglobin enzyme that catalyzes the production of taurine through the cysteine (Cys) pathway and plays a key role in the biosynthesis of taurine in mammals. However, the function of CDOs in bony fish remains poorly understood. In this study, we cloned CDO genes (CaCDO1 and CaCDO2) from Carassius auratus. The cDNA sequences of both CaCDO1 and CaCDO2 encoded putative proteins with 201 amino acids, which included structural features typical of the CDO protein family. Multiple sequence alignment and phylogenetic analysis showed that CaCDO1 and CaCDO2 shared high sequence identities and similarities with C. carpio homologs. Quantitative real-time polymerase chain reaction (qRT-PCR) results revealed that CaCDO1 and CaCDO2 were both broadly expressed in all selected tissues and developmental stages in C. auratus but had differing mRNA levels. In addition, compared to those of the taurine-free group, the in vivo mRNA expression levels of both CaCDO1 and CaCDO2 significantly decreased with increasing dietary taurine levels from 1.0 to 9.0â¯g/kg. Furthermore, in vitro taurine treatments showed similar inhibitory effects on the expression of CaCDO1 and CaCDO2 in the intestines of C. auratus. Our results also showed that the mRNA expression of CaCDO2 in the intestines was higher than that of CaCDO1 in response to in vivo and in vitro taurine supplementation. Overall, these data may provide new insights into the regulation of fish CDO expression and provide valuable knowledge for improving dietary formulas in aquaculture.
Assuntos
Cisteína Dioxigenase/genética , Cisteína Dioxigenase/metabolismo , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Carpa Dourada/genética , Carpa Dourada/metabolismo , Taurina/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , DNA Complementar/genética , Regulação da Expressão Gênica no Desenvolvimento , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Carpa Dourada/crescimento & desenvolvimento , Isoenzimas/genética , Isoenzimas/metabolismo , Filogenia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Taurina/farmacologia , Distribuição TecidualRESUMO
Cardiac hypertrophy is characterized by myocyte hypertrophy, accumulation of cardiac collagen, and reactivation of fetal genes. Maslinic acid (MA) is a pentacyclic triterpene with abundance in olive fruit skin and possesses a number of pharmacological actions. However, its effect on pressure overload-induced cardiac hypertrophy remains unknown. Here, we were to investigate the protective effect of MA on cardiac hypertrophy and fibrosis. C57 mice were subjected to aortic banding (AB) or sham surgery. One day after surgery, all the mice were orally given MA (20 mg/kg) or vehicle for the following four weeks. MA could protect against pressure overload-induced cardiac hypertrophy and cardiac fibrosis, as indicated by decreased heart weight/tibia length, and cardiomyocytes cell area and hypertrophic and fibrotic markers. MA treatment also improved cardiac function in mice with AB surgery, as assessed by echocardiographic and hemodynamic analysis. MA reduced phosphorylation of protein kinase B and extracellular regulated protein kinases in the hypertrophic hearts. MA could decrease cardiomyocyte hypertrophy, and inhibit the activation of AKT and ERK signaling pathway in vitro. In conclusion, we found that MA protected against cardiac hypertrophy. MA has the potential to become a therapeutic drug for cardiac hypertrophy.
Assuntos
Cardiomegalia/tratamento farmacológico , Cardiomegalia/etiologia , Fitoterapia , Pressão/efeitos adversos , Triterpenos/administração & dosagem , Administração Oral , Animais , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Células Cultivadas , Modelos Animais de Doenças , Fibrose , Hemodinâmica , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/patologia , Olea/química , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Triterpenos/isolamento & purificaçãoRESUMO
Realgar (As4S4), as an arsenic sulfide mineral drug, has a good therapeutic reputation for anticancer in Traditional Chinese Medicine, and has recently been reported to inhibit angiogenesis in tumor growth. However, considering the poor solubility and low bioavailability of realgar, large dose of realgar and long period of treatment are necessary for achieving the effective blood medicine concentration. In present study, we resolved the crucial problem of poor solubility of realgar by using intrinsic biotransformation in microorganism, and investigated underlying mechanisms of realgar transforming solution (RTS) for antiangiogenesis. Our results demonstrated that RTS had a strong activity to inhibit HUVECs proliferation, migration, invasion, and tube formation. Moreover, RTS inhibited VEGF/bFGF-induced phosphorylation of VEGFR2 and the downstream protein kinases including ERK, FAK, and Src. In vivo zebrafish and chicken chorioallantoic membrane model experiments showed that RTS remarkably blocked angiogenesis. Finally, compared with the control, administration of 2.50 mg/kg RTS reached more than 50% inhibition against H22 tumor allografts in KM mice, but caused few toxic effects in the host. The antiangiogenic effect was indicated by CD31 immunohistochemical staining and alginate-encapsulated tumor cell assay. In summary, our findings suggest that RTS inhibits angiogenesis and may be a potential drug candidate in anticancer therapy.
Assuntos
Inibidores da Angiogênese/farmacologia , Arsenicais/farmacologia , Carcinogênese/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Sulfetos/farmacologia , Carga Tumoral/efeitos dos fármacos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Inibidores da Angiogênese/uso terapêutico , Animais , Arsenicais/uso terapêutico , Carcinogênese/metabolismo , Carcinogênese/patologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Feminino , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Camundongos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Transdução de Sinais , Sulfetos/uso terapêutico , Carga Tumoral/fisiologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Peixe-ZebraRESUMO
Realgar (As4S4), as a mineral drug containing arsenic compound, has been employed in clinical therapy of cancer for its good therapeutic reputation in Chinese traditional medicine. However, large dose of realgar and long period of treatment are necessary for achieving the effective blood medicine concentration due to its low bioavailability resulted from poor solubility. In this study, we obtained realgar transforming solution (RTS) using intrinsic biotransformation in microorganism, and investigated underlying mechanisms of RTS for HepG2 cells. Our results demonstrated that an effective biotransformation of realgar method by A. ferrooxidans was established, in which realgar was biologically converted into an aqueous solution, and RTS had a strong activity inducing apoptosis and interrupting G2/M progression in HepG2 cells via upregulation of cellular ROS. Importantly, RTS inhibited the cellular antioxidant defense system leading to abundant ROS accumulation, and activated cell cycle arrest and mitochondrial pathway of apoptosis mediated by activating p53 due to cellular uncontrolled ROS. Collectively, our findings suggest that RTS is a potential candidate for therapy of human hepatocellular carcinoma.
Assuntos
Acidithiobacillus/metabolismo , Antineoplásicos/farmacologia , Arsenicais/farmacologia , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Apoptose , Arsenicais/química , Biodegradação Ambiental , Carcinoma Hepatocelular/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Medicina Tradicional Chinesa , Sulfetos/químicaRESUMO
This study was designed to investigate the impact of ultra-filtration extract mixture from Astragals mongholicus (UEMAM) o radiosensitivity of H22 ascitic tumor in mice to 12C6+ ions radiation. The H22 ascitic tumor model was established in mice by intraperitoneal injection of 0.2 mL H22 ascitic cells. The animals were subsequently divided into 4 groups randomly, treated with normal saline, UEMAM, heavy ion beam radiotherapy and UEMAM plus heavy ion beam radiotherapy, respectively. The body weights, abdomen circumference of the mice were measured and the mouse behavior was monitored every day; survival time was recorded to evaluate life extension effect; flow cytometry technique was used to detect H22 cell apoptosis and cell cycle; protein levels of p53, Bax, Bcl-2 and cleaved Caspase-3 were analyzed by Western blot; the single cell gel electrophoresis was used to detect the level of deoxyribonucleic acid damage (DNA damage). The results suggest that UEMAM significantly increased survival time, and decreased body weights and abdomen circumference over the saline control group. The treatment increased cell apoptosis, cycle arrest and DNA damage compared to the saline control group. UEMAM significantly enhanced the therapeutic effect of heavy ion beam radiation in survival time, and decreased body weights and abdomen circumference in the tumor-baring mice. The combination increased cell apoptosis, cycle arrest and DNA damage compared to the radiotherapy group. The results of Western blot suggest that the treatment significantly enhanced p53-induced apoptotic signals. The experiment discovered that UEMAM could improve radiosensitivity of H22 ascitic tumor through activation of p53-mediated apoptotic signal pathway.
Assuntos
Astrágalo/química , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/radioterapia , Extratos Vegetais/farmacologia , Tolerância a Radiação , Animais , Apoptose , Ciclo Celular , Linhagem Celular Tumoral , Dano ao DNA , Íons , Camundongos , Transdução de SinaisRESUMO
OBJECTIVE: To compare the effects of 8-prenylnaringenin (PNG) and naringenin (NG) on the activity and apoptosis of osteoclasts cultured in vitro, in order to study physiological activity of 8-prenyl perssad. METHOD: Osteoclasts were separated from long-limb bones of newly born rabbits, cultured in alpha-MEM containing 10% FBS, and then added with PNG and NG with the concentration of 1 x 10(-5) mol x L(-1). They were stained with TRAP and determined for enzymatic activity with TRAP after 4 d, and analyzed by toluidine blue staining after 7 d. The apoptotic osteoclasts were analyzed by Annexin V-FITC staining after 2, 4, 8, 12, 24, 36, and 48 hours, to observe their apoptosis. Their total RNAs were extracted, and analyzed for TRAP and Cathepsin K expressions by Real-time RT-PCR. RESULT: Compared with the control group, both of the PNG group and the NG group showed much less osteoclasts (TRAP positive cells), lower TRAP activity and TRAP and Cathepin K (CTSK) expression, and smaller number of bone resorption pits and areas. The PNG group show lower indexes than the NG group. Additionally, the PNG group reached the apoptotic peak of osteoclasts at 12 h after drug administration, whereas the NG group reached after 24 h. And the former had more apoptotic cells than the latter. CONCLUSION: 8-PNG is much more active than NG in inhibiting the resorption of osteoclasts and inducing apoptosis of osteoclasts. Their only difference lies in 8-prenyl perssad, which is proved to be able to enhance the anti-bone resorption activity of 8-prenylnarigenin.
Assuntos
Flavanonas/farmacologia , Osteoclastos/efeitos dos fármacos , Fosfatase Ácida/metabolismo , Animais , Reabsorção Óssea/prevenção & controle , Catepsina K/metabolismo , Células Cultivadas , CoelhosRESUMO
BACKGROUND: Budd-Chiari syndrome (BCS) often leads to hepatocellular carcinoma (HCC). Transcatheter arterial chemoembolization (TACE) has been increasingly used to treat BCS patients with HCC. The purposes of this study were to illustrate imaging features in BCS patients with HCC, and to analyze the effects of TACE on BCS patients with HCC. METHODS: 246 consecutive patients with primary BCS were retrospectively studied. 14 BCS patients with HCC were included in this study. BCS were treated with angioplasty and/or stenting, and HCC were managed with TACE. Imaging features on ultrasonography, CT, MRI, and angiography and the serum AFP level were analyzed. RESULTS: Inferior vena cava block and stricture of hepatic venous outflow tract more frequently occurred. Portal vein invasion was found in only 2 patients (14.2%). Imaging studies showed that most nodules of HCC were near the edge of liver, irregular, more than 3 cm in diameter, heterogeneous mass and solitary (≤3 nodules). HCC in patients associated with BCS was isointense or hypointense in nonenhanced CT images, and exhibited heterogeneous enhancement during the arterial phase and washout during the portal venous phase on enhanced CT and MRI. The serum AFP level significantly declined after TACE treatment. CONCLUSIONS: BCS patients with inferior vena cava block and stricture of hepatic venous outflow tract seems to be associated with HCC. A single, large, irregular nodule with a peripheral location appears to be HCC. TACE can effectively treat HCC in BCS patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Síndrome de Budd-Chiari/terapia , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Adulto , Angiografia , Angioplastia , Síndrome de Budd-Chiari/complicações , Síndrome de Budd-Chiari/diagnóstico , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/diagnóstico , Epirubicina/administração & dosagem , Óleo Etiodado/administração & dosagem , Feminino , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Estudos Retrospectivos , Stents , alfa-Fetoproteínas/metabolismoRESUMO
Previous studies have found that 8-prenylflavonoids have a higher osteogenic activity than do flavonoids, which suggested that the 8-prenyl group may play an active role in bone-protective properties. To address this hypothesis, activities of 8-prenylnaringenin (PNG) and naringenin (NG) in osteoblast and osteoclast differentiation and function were compared in vitro. PNG was found to have a stronger ability than NG to improve osteoblast differentiation and osteogenic function in cultured rat calvarial osteoblasts, as demonstrated by levels of alkaline phosphatase activity, osteocalcin, calcium deposition, and the number and area of mineralized bone nodules, as well as mRNA expression of osteogenesis-related genes Bmp-2, OSX, and Runx-2. In addition, although expression of osteoclastogenic inducer receptor activator of nuclear factor kappa-B ligand (RANKL) was not affected, that of osteoclastogenesis inhibitor osteoprotegerin (OPG) and consequently the OPG/RANKL ratio were increased, more potently by PNG than NG. PNG was also found to have a higher potency than NG in inhibiting the osteoclast formation in rabbit bone marrow cells and their resorptive activity, as revealed by lower numbers of osteoclasts formed, lower numbers and areas of bone resorption pits, and lower mRNA expression levels of tartrate-resistant acid phosphatase and cathepsin K. Furthermore, PNG induced apoptosis of mature osteoclasts at a higher degree and at an earlier time than did NG. These results indicate that the 8-prenyl group plays an important role and contributes to the higher bone-protective activity of PNG in comparison with NG.