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Pyrrolizidine alkaloids (PAs) are one type of phytotoxins distributed in various plants, including many medicinal herbs. Many organs might suffer injuries from the intake of PAs, and the liver is the most susceptible one. The diagnosis, toxicological mechanism, and detoxification of PAs-induced hepatotoxicity have been studied for several decades, which is of great significance for its prevention, diagnosis, and therapy. When the liver was exposed to PAs, liver sinusoidal endothelial cells (LSECs) loss, hemorrhage, liver parenchymal cells death, nodular regeneration, Kupffer cells activation, and fibrogenesis occurred. These pathological changes classified the PAs-induced liver injury as acute, sub-acute, and chronic type. PAs metabolic activation, mitochondria injury, glutathione (GSH) depletion, inflammation, and LSECs damage-induced activation of the coagulation system were well recognized to play critical roles in the pathological process of PAs-induced hepatotoxicity. A lot of natural compounds like glycyrrhizic acid, (-)-epicatechin, quercetin, baicalein, chlorogenic acid, and so on were demonstrated to be effective in alleviating PAs-induced liver injury, which rendered them huge potential to be developed into therapeutic drugs for PAs poisoning in clinics. This review presents updated information about the diagnosis, toxicological mechanism, and detoxification studies on PAs-induced hepatotoxicity.
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Doença Hepática Crônica Induzida por Substâncias e Drogas , Plantas Medicinais , Alcaloides de Pirrolizidina , Alcaloides de Pirrolizidina/toxicidade , Alcaloides de Pirrolizidina/metabolismo , Plantas Medicinais/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Doença Hepática Crônica Induzida por Substâncias e Drogas/patologia , Glutationa/metabolismo , Extratos VegetaisRESUMO
Triple-negative breast cancer (TNBC) is incurable and prone to widespread metastasis. Therefore, identification of key targets for TNBC progression is urgently needed. Our previous study revealed that isotoosendanin (ITSN) reduced TNBC metastasis by targeting TGFßR1. ITSN is currently used as an effective chemical probe to further discover the key molecules involved in TNBC metastasis downstream of TGFßR1. The results showed that GOT2 was the gene downstream of Smad2/3 and that ITSN decreased GOT2 expression by abrogating the activation of the TGF-ß-Smad2/3 signaling pathway through directly binding to TGFßR1. GOT2 was highly expressed in TNBC, and its knockdown decreased TNBC metastasis. However, GOT2 overexpression reversed the inhibitory effect of ITSN on TNBC metastasis both in vitro and in vivo. GOT2 interacted with MYH9 and hindered its binding to the E3 ubiquitin ligase STUB1, thereby reducing MYH9 ubiquitination and degradation. Moreover, GOT2 also enhanced the translocation of MYH9 to mitochondria and thus induced DRP1 phosphorylation, thereby promoting mitochondrial fission and lamellipodia formation in TNBC cells. ITSN-mediated inhibition of mitochondrial fission and lamellipodia formation was associated with reduced GOT2 expression. In conclusion, ITSN prevented MYH9-regulated mitochondrial fission and lamellipodia formation in TNBC cells by enhancing MYH9 protein degradation through a reduction in GOT2 expression, thus contributing to its inhibition of TNBC metastasis.
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Hepatic sinusoidal obstruction syndrome (HSOS) is a death-dealing liver disease with a fatality rate of up to 67%. In the study present, we explored the efficacy of andrographolide (Andro), a diterpene lactone from Andrographis Herba, in ameliorating the monocrotaline (MCT)-induced HSOS and the underlying mechanism. The alleviation of Andro on MCT-induced rats HSOS was proved by biochemical index detection, electron microscope observation, and liver histological evaluation. Detection of hepatic ATP content, mitochondrial DNA (mtDNA) copy number, and protein expression of nuclear respiratory factor-1 (NRF1) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) demonstrated that Andro strengthened mitochondrial biogenesis in livers from MCT-treated rats. Chromatin immunoprecipitation assay exhibited that Andro enhanced the occupation of nuclear factor erythroid 2-related factor 2 (NFE2L2, also known as NRF2) in the promoter regions of both PPARGC1A and NRF1. Andro also activated the NRF2-dependent anti-oxidative response and alleviated liver oxidative injury. In Nrf2 knock-out mice, MCT induced more severe liver damage, and Andro showed no alleviation in it. Furthermore, the Andro-activated mitochondrial biogenesis and anti-oxidative response were reduced in Nrf2 knock-out mice. Contrastingly, knocking out Kelch-like ECH-associated protein 1 (Keap1), a NRF2 repressor, reduced MCT-induced liver damage. Results from co-immunoprecipitation, molecular docking analysis, biotin-Andro pull-down, cellular thermal shift assay, and surface plasmon resonance assay showed that Andro hindered the NRF2-KEAP1 interaction via directly binding to KEAP1. In conclusion, our results revealed that NRF2-dependent liver mitochondrial biogenesis and anti-oxidative response were essential for the Andro-provided alleviation of the MCT-induced HSOS. Graphical Headlights: 1. Andro alleviated MCT-induced HSOS via activating antioxidative response and promoting mitochondrial biogenesis. 2. Andro-activated antioxidative response and mitochondrial biogenesis were NRF2-dependent. 3. Andro activated NRF2 via binding to KEAP1.
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Diterpenos , Hepatopatia Veno-Oclusiva , Camundongos , Ratos , Animais , Hepatopatia Veno-Oclusiva/induzido quimicamente , Hepatopatia Veno-Oclusiva/metabolismo , Hepatopatia Veno-Oclusiva/patologia , Antioxidantes/farmacologia , Monocrotalina/efeitos adversos , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Simulação de Acoplamento Molecular , Biogênese de Organelas , Diterpenos/farmacologia , Estresse Oxidativo , Camundongos Knockout , DNA Mitocondrial/metabolismoRESUMO
OBJECTIVES: To build and validate deep learning and machine learning fusion models to classify benign, malignant, and intermediate bone tumors based on patient clinical characteristics and conventional radiographs of the lesion. METHODS: In this retrospective study, data were collected with pathologically confirmed diagnoses of bone tumors between 2012 and 2019. Deep learning and machine learning fusion models were built to classify tumors as benign, malignant, or intermediate using conventional radiographs of the lesion and potentially relevant clinical data. Five radiologists compared diagnostic performance with and without the model. Diagnostic performance was evaluated using the area under the curve (AUC). RESULTS: A total of 643 patients' (median age, 21 years; interquartile range, 12-38 years; 244 women) 982 radiographs were included. In the test set, the binary category classification task, the radiological model of classification for benign/not benign, malignant/nonmalignant, and intermediate/not intermediate had AUCs of 0.846, 0.827, and 0.820, respectively; the fusion models had an AUC of 0.898, 0.894, and 0.865, respectively. In the three-category classification task, the radiological model achieved a macro average AUC of 0.813, and the fusion model had a macro average AUC of 0.872. In the observation test, the mean macro average AUC of all radiologists was 0.819. With the three-category classification fusion model support, the macro AUC improved by 0.026. CONCLUSION: We built, validated, and tested deep learning and machine learning models that classified bone tumors at a level comparable with that of senior radiologists. Model assistance may somewhat help radiologists' differential diagnoses of bone tumors. KEY POINTS: ⢠The deep learning model can be used to classify benign, malignant, and intermediate bone tumors. ⢠The machine learning model fusing information from radiographs and clinical characteristics can improve the classification capacity for bone tumors. ⢠The diagnostic performance of the fusion model is comparable with that of senior radiologists and is potentially useful as a complement to radiologists in a bone tumor differential diagnosis.
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Neoplasias Ósseas , Aprendizado Profundo , Adulto , Neoplasias Ósseas/diagnóstico por imagem , Feminino , Humanos , Aprendizado de Máquina , Radiografia , Estudos Retrospectivos , Adulto JovemRESUMO
Due to hot toxic smoke and unknown risks under fire conditions, detection and relevant reconnaissance are significant in avoiding casualties. A fire reconnaissance robot was therefore developed to assist in the problem by offering important fire information to fire fighters. The robot consists of three main systems, a display operating system, video surveillance, and mapping and positioning navigation. Augmented reality (AR) goggle technology with a display operating system was also developed to free fire fighters' hands, which enables them to focus on rescuing processes and not system operation. Considering smoke disturbance, a thermal imaging video surveillance system was included to extract information from the complicated fire conditions. Meanwhile, a simultaneous localization and mapping (SLAM) technology was adopted to build the map, together with the help of a mapping and positioning navigation system. This can provide a real-time map under the rapidly changing fire conditions to guide the fire fighters to the fire sources or the trapped occupants. Based on our experiments, it was found that all the tested system components work quite well under the fire conditions, while the video surveillance system produces clear images under dense smoke and a high-temperature environment; SLAM shows a high accuracy with an average error of less than 3.43%; the positioning accuracy error is 0.31 m; and the maximum error for the navigation system is 3.48%. The developed fire reconnaissance robot can provide a practically important platform to improve fire rescue efficiency to reduce the fire casualties of fire fighters.
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The ceiling structure in a long-narrow space has a significant impact on the thickness of the fire smoke layer. This paper mainly studies the influence of the height of the ceiling structure on the thickness of the smoke layer before the ceiling structure. Firstly, a theoretical analysis is conducted on the relationship between the critical thickness that affects the smoke flow state and the smoke layer thickness directly below the ceiling structure, and a formula for calculating the smoke layer thickness under gradient flow conditions is derived. Then a small-scale experimental platform was built to study the deviation of actual fire smoke relative to theoretical calculations. Experimental results show that due to the smoke cannot maintain gradient flow when crossing the ceiling structure, there is difference with theoretical calculations in the smoke layer thickness directly below the ceiling structure and some distance before the ceiling structure (which may be of greater concern for personnel evacuation). The gradient flow coefficient and thickness coefficient are defined to represent the above differences. After analysis, it was found that the gradient flow coefficient and thickness coefficient showed different linear variation patterns when the height of the ceiling structure was longer than 35 cm or shorter than 30 cm. Through numerical analysis, this study suggests that the main reason for the change in this linear pattern is whether the potential energy conversed from kinetic energy of the thin layer close to the ceiling structure can directly make the smoke to cross the ceiling structure. The research conclusions of this paper can assist in the engineering design of building smoke control and personnel evacuation.
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Liver fibrosis is a key and reversible stage in the progression of many chronic liver diseases to cirrhosis or hepatocellular carcinoma. Forsythiaside-A (FTA), a main compound isolated from Forsythiae Fructus, has an excellent liver protective activity. This study aims to investigate the efficacy of FTA in improving cholestatic liver fibrosis. Bile-duct-ligation (BDL) was conducted to induce liver fibrosis in mice. Hepatic collagen deposition was evaluated by Masson and Sirus red staining. The bile acid spectrum in the liver and serum was analyzed by mass spectrometry. Liver oxidative stress injury and mitochondria damage were observed by using Mito-Tracker Red fluorescence staining, transmission electron microscopy, etc. The level of ferrous iron (Fe2+) and the expression of ferroptosis-associated molecules were detected. The binding between FTA and its target protein was confirmed by Co-immunoprecipitation (Co-IP), cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) and surface plasmon resonance (SPR). Our results demonstrated that FTA alleviated BDL-induced liver fibrosis in mice. FTA did not decrease the elevated amount of bile acids in BDL-treated mice, but reduced the bile acid-induced mitochondrial damage, oxidative stress and ferroptosis in hepatocytes, and also induced nuclear factor erythroid 2-related factor-2 (Nrf2) activation. In Nrf2 knock-out mice, the FTA-provided protection against BDL-induced liver fibrosis was disappeared, and FTA's inhibition on mitochondrial damage, oxidative stress and ferroptosis were lowered. Further results displayed that FTA could directly bind to Kelch-like ECH-associated protein-1 (Keap1), thereby activating Nrf2. Moreover, the BDL-induced liver fibrosis was markedly weakened in liver-specific Keap1 knockout mice. Hence, this study suggests that FTA alleviated the BDL-induced liver fibrosis through attenuating mitochondrial damage and ferroptosis in hepatocytes by activating Nrf2 via directly binding to Keap1.
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Ferroptose , Hepatócitos , Cirrose Hepática , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Animais , Humanos , Masculino , Camundongos , Ductos Biliares/patologia , Ductos Biliares/cirurgia , Ductos Biliares/metabolismo , Ferroptose/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Hepatócitos/efeitos dos fármacos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Ligadura , Cirrose Hepática/patologia , Cirrose Hepática/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Mitocôndrias/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/efeitos dos fármacosRESUMO
Immobilization and stabilization of heavy metals (HMs) in sulfidic and metallic tailings are critical to long-term pollution control and sustainable ecological rehabilitation. This study aims to unravel immobilization mechanisms of Pb (â ¡) in the neoformed hardpan structure resulting from Acidithiobacillus spp. accelerated bioweathering of sulfides in the presence of silicates. It was found that the bioweathered mineral composite exhibited an elevated Pb (â ¡) adsorption capacity compared to that of natural weathered mineral composite. A suit of microspectroscopic techniques such as synchrotron-based X-ray Absorption Spectroscopy (XAS), X-ray Photoelectron Spectroscopy (XPS), Fourier Transform Infrared Spectroscopy (FTIR) and Field-Emission Scanning Electron Microscope (FE-SEM) indicated that secondary Fe-bearing minerals, functional groups, and surface properties in the neoformed hardpan were key factors contributing to Pb (â ¡) adsorption and immobilization in ferric-silica microstructures. The underlying mechanisms might involve surface adsorption-complexation, dissolution-precipitation, electrostatic attraction, and ion exchange. Microbial communities within the muscovite groups undergoing bioweathering processes demonstrated distinctive survival strategies and community composition under the prevailing geochemical conditions. This proof of concept regarding Pb (â ¡) immobilization in microbial transformed mineral composite would provide the basis for scaling up trials for developing field-feasible methodology to management HMs pollution in sulfidic and metallic tailings in near future.
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Acidithiobacillus , Chumbo , Dióxido de Silício , Dióxido de Silício/química , Acidithiobacillus/metabolismo , Adsorção , Compostos Férricos/química , Poluentes do Solo , Mineração , Minerais/química , Sulfetos/químicaRESUMO
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterized by the abnormal proliferation of fibroblast and excessive deposition of extracellular matrix (ECM), accompanied by inflammation and ultimately respiratory failure. Yinhuang granule (YHG), with clinical properties of clearing heat, detoxifying and anti-inflammation, is commonly used to heal upper respiratory diseases in China for decades. PURPOSE: To explore the improvement of YHG on bleomycin (BLM)-induced IPF in mice and its possible engaged mechanism. METHODS: The mortality rate was recorded, lung function was determined and hematoxylin-eosin (H&E) staining was carried out to explore the alleviation of YHG on BLM-caused IPF in mice. Hydroxyproline, collagen I and collagen III contents were detected, and Sirius red and Masson staining were conducted to evaluate YHG's alleviation on lung fibrosis. The underlying mechanism was predicted by network pharmacology, and confirmed by Real-time polymerase chain reaction (RT-PCR), Western-blot (WB) and enzyme linked immunosorbent assay (ELISA). The binding affinity between related key proteins and active compounds in YHG was calculated by using molecular docking, and further validated by cellular thermal shift assay (CESTA). RESULTS: YHG (400, 800 mg/kg) weakened lung damage and pulmonary fibrosis in mice induced by BLM. Network pharmacology and experimental validation displayed that inflammation and angiogenesis participated in the YHG-provided improvement on IPF, and key involved molecules included tumor necrosis factor-α (TNFα), vascular endothelial growth factor-A (VEGFA), interleukine-6 (IL-6), etc. The data of molecular docking presented that some main active compounds from YHG had a high binding affinity with TNFR1 or VEGFR2, and some of them were further validated by CESTA. CONCLUSION: YHG effectively improved the BLM-induced IPF in mice via reducing inflammation and angiogenesis.
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Bleomicina , Medicamentos de Ervas Chinesas , Fibrose Pulmonar Idiopática , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fator A de Crescimento do Endotélio Vascular , Animais , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/induzido quimicamente , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Camundongos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Masculino , Fator de Necrose Tumoral alfa/metabolismo , Humanos , Pulmão/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Modelos Animais de DoençasRESUMO
Hardpan-based profiles naturally formed under semi-arid climatic conditions have substantial potential in rehabilitating sulfidic tailings, resulting from their aggregation microstructure regulated by Fe-Si cements. Nevertheless, eco-engineered approaches for accelerating the formation of complex cementation structure remain unclear. The present study aims to investigate the microbial functions of extremophiles on mineral dissolution, oxidation, and aggregation (cementation) through a microcosm experiment containing pyrites and polysilicates, of which are dominant components in typical sulfidic tailings. Microspectroscopic analysis revealed that pyrite was rapidly dissolved and massive microbial corrosion pits were displayed on pyrite surfaces. Synchrotron-based X-ray absorption spectroscopy demonstrated that approximately 30 % pyrites were oxidized to jarosite-like (ca. 14 %) and ferrihydrite-like minerals (ca. 16 %) in talc group, leading to the formation of secondary Fe precipitates. The Si ions co-dissolved from polysilicates may be embedded into secondary Fe precipitates, while these clustered Fe-Si precipitates displayed distinct morphology (e.g., "circular" shaped in the talc group, "fine-grained" shaped in the chlorite group, and "donut" shaped in the muscovite group). Moreover, the precipitates could join together and act as cementing agents aggregating mineral particles together, forming macroaggregates in talc and chlorite groups. The present findings revealed critical microbial functions on accelerating mineral dissolution, oxidation, and aggregation of pyrite and various silicates, which provided the eco-engineered feasibility of hardpan-based technology for mine site rehabilitation.
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Acidithiobacillus , Cloretos , Ferro , Dióxido de Silício , Sulfetos , Talco , Minerais/química , Eletrólitos , Ferro da DietaRESUMO
As the most aggressive breast cancer, triple-negative breast cancer (TNBC) is still incurable and very prone to metastasis. The transform growth factor ß (TGF-ß)-induced epithelial-mesenchymal transition (EMT) is crucially involved in the growth and metastasis of TNBC. This study reported that a natural compound isotoosendanin (ITSN) reduced TNBC metastasis by inhibiting TGF-ß-induced EMT and the formation of invadopodia. ITSN can directly interact with TGF-ß receptor type-1 (TGFßR1) and abrogated the kinase activity of TGFßR1, thereby blocking the TGF-ß-initiated downstream signaling pathway. Moreover, the ITSN-provided inhibition on metastasis obviously disappeared in TGFßR1-overexpressed TNBC cells in vitro as well as in mice bearing TNBC cells overexpressed TGFßR1. Furthermore, Lys232 and Asp351 residues in the kinase domain of TGFßR1 were found to be crucial for the interaction of ITSN with TGFßR1. Additionally, ITSN also improved the inhibitory efficacy of programmed cell death 1 ligand 1 (PD-L1) antibody for TNBC in vivo via inhibiting the TGF-ß-mediated EMT in the tumor microenvironment. Our findings not only highlight the key role of TGFßR1 in TNBC metastasis, but also provide a leading compound targeting TGFßR1 for the treatment of TNBC metastasis. Moreover, this study also points out a potential strategy for TNBC treatment by using the combined application of anti-PD-L1 with a TGFßR1 inhibitor.
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BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is becoming more and more common in clinic in the world, and the study on its mechanism and treatment strategy has already been a research hotspot. Natural chemical compound 2,3,5,4'-tetrahydroxy-stilbene-2-O-ß-d-glucoside (TSG) is isolated from Polygonum multiflorum Thunb. that has already been reported to have the lipid-lowering activity. PURPOSE: The purpose of this research was to observe the improvement of TSG on methionine and choline deficient (MCD) diet-induced NAFLD in mice and to further elucidate its engaged mechanism. METHODS: NAFLD was induced in mice fed by MCD diet for 6 weeks. The accumulation of lipids in hepatocytes was induced by 0.5 mM non-esterified fatty acid (NEFA). Biochemical parameters in serum or livers from mice were tested. Protein and mRNA expression and stability were measured. Mitochondrial dysfunction was analyzed both in vivo and in vitro. The Label-free quantitative proteomic analysis was used to find potential involved key molecules. RESULTS: TSG attenuated hepatic parenchymal cells injury, liver inflammatory responses and hepatic fibrosis, and markedly ameliorated liver steatosis in mice from MCD group. In vitro results indicated that TSG reduced the accumulation of cellular lipids in hepatocytes induced by NEFA. TSG reduced reactive oxygen species (ROS) formation and attenuated mitochondrial dysfunction both in vivo and in vitro. The label-free quantitative proteomic analysis predicted the crucial participation of NAD-dependent protein deacylase sirtuin-5 (SIRT5). Next experimental results further evidenced that TSG enhanced SIRT5 expression in mitochondria both in vitro and in vivo. The TSG-supplied inhibition on ROS formation and mitochondrial dysfunction in hepatocytes was disappeared after the application of SIRT5 siRNA. TSG increased the expression and enzymatic activity of carnitine palmitoyltransferase 1A (CPT1A), but this enhance was diminished in hepatocytes transfected with SIRT5 siRNA. Additionally, the TSG-provided inhibition on cellular lipids accumulation was also disappeared in hepatocytes transfected with SIRT5 siRNA. Further results demonstrated that TSG increased SIRT5 expression by regulating its mRNA stability through enhancing the binding of SIRT5 mRNA with serine/arginine-rich splicing factor 2 (SRSF2), which is an RNA-binding protein (RBP). CONCLUSION: TSG attenuated liver steatosis and inhibited NAFLD progression through preventing oxidative stress injury and improving mitochondrial dysfunction, and SIRT5 played a key role in this process.
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Eupalinolide J (EJ) is a new sesquiterpene lactone isolated from Eupatorium lindleyanum DC. In the present study, we investigated the anti-cancer activity of EJ on cell proliferation in human prostate cancer cells. The MTT results indicated that EJ showed marked anti-proliferative activity in PC-3 and DU-145 cells in a dose- and time-dependent manner. DAPI staining analysis demonstrated that this effect was mediated by induction of cell apoptosis. Flow cytometric analysis indicated a significant increase in apoptotic cells, cell cycle arrest at G0/G1 phase and disruption of mitochondrial membrane potential (MMP) after EJ treatment. Meanwhile, the activation of caspase-3 and caspase-9 was visibly observed. Furthermore, our results demonstrated that the expression levels of γH2AX, p-Chk1 and p-Chk2 were significantly up-regulated, suggesting the induction of DNA damage responses in EJ-treated prostate cancer cells. The above results indicated that EJ exhibited effective anti-cancer activity in vitro. It could be a promising candidate agent for the clinical treatment of prostate cancer.
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Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Potenciais da Membrana/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Eupatorium/química , Humanos , Masculino , Células Tumorais CultivadasRESUMO
Valtrate is a principle compound isolated from Valeriana jatamansi Jones, a traditional Chinese folk medicine originally used to treat various nervous disorders. Here, we found that valtrate exhibited significant anti-cancer activity in vitro, especially in human breast cancer cells, while displayed relatively low cytotoxicity to normal human breast epithelial cells (MCF 10A). Valtrate induced cell cycle arrest at G2/M stage and apoptosis in MDA-MB-231 and MCF-7 cells, with reduced expression of p-Akt (Ser 473), cyclin B1 and caspase 8, and increased expression of p21, p-cdc2, cleaved-caspase 3, cleaved-caspase 7 and poly (ADP-ribose) polymerase (PARP). In addition, valtrate inhibited cell migration through down-regulation of MMP-9 and MMP-2 expression. These results demonstrate that valtrate possesses anti-breast cancer activities via cell cycle arrest, apoptosis, and inhibition of cell migration, thus supporting valtrate as a potential antitumor agent.
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Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Movimento Celular/efeitos dos fármacos , Iridoides/farmacologia , Valeriana/química , Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Caspase 8/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Humanos , Iridoides/isolamento & purificação , Células MCF-7RESUMO
A functionalized paper based on gold nanoparticles (Au NPs) conjugated graphene oxide (GO) was developed for near-infrared (NIR) laser triggered photothermal ablation against infectious bacterial pathogens. Firstly, quaternized carboxymethyl chitosan (QCMC) not only acted as reducing agent to synthesize Au NPs, but also functioned as coupling agent to link up Au NPs with GO. Au-QCMC-GO(+) was supposed to synergistically intensify the photothermal effect, which was then mixed with nanocellulose to form a functionalized paper via vacuum filtration. The photothermal efficiency, antibacterial treatment and mechanical property of Au-QCMC-GO(+)/nanocellulose paper were investigated. Excited by NIR laser irradiation, Au-QCMC-GO(+)/nanocellulose paper generated a temperature rise over 80⯰C, sufficient for photothermal ablation upon both Gram-positive bacteria (Bacillus subtilis and Stapylococcus aureus) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Additionally, Au-QCMC-GO(+)/nanocellulose paper showed a remarkable enhancement in tensile strength, bursting index and tear index compared to those of pure nanocellulose paper.