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1.
Front Immunol ; 12: 688910, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34177945

RESUMO

Lactate is an end product of glycolysis. As a critical energy source for mitochondrial respiration, lactate also acts as a precursor of gluconeogenesis and a signaling molecule. We briefly summarize emerging concepts regarding lactate metabolism, such as the lactate shuttle, lactate homeostasis, and lactate-microenvironment interaction. Accumulating evidence indicates that lactate-mediated reprogramming of immune cells and enhancement of cellular plasticity contribute to establishing disease-specific immunity status. However, the mechanisms by which changes in lactate states influence the establishment of diverse functional adaptive states are largely uncharacterized. Posttranslational histone modifications create a code that functions as a key sensor of metabolism and are responsible for transducing metabolic changes into stable gene expression patterns. In this review, we describe the recent advances in a novel lactate-induced histone modification, histone lysine lactylation. These observations support the idea that epigenetic reprogramming-linked lactate input is related to disease state outputs, such as cancer progression and drug resistance.


Assuntos
Ácido Láctico/metabolismo , Acetilcoenzima A/metabolismo , Animais , Epigênese Genética , Histonas/metabolismo , Humanos , Ácido Láctico/imunologia , Microambiente Tumoral
2.
Zhongguo Zhong Yao Za Zhi ; 45(12): 2784-2791, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32627451

RESUMO

Jiaotai Pills is a traditional medical prescription to treat the incompatibility of heart and kidney. It has the distinctive functions of heart and kidney communication, sedation and hypnosis, anti-anxiety and depression, as well as the improvement of insulin resistance. However, this pill is broadly used to cure insomnia, anxiety, depression, and diabetes in the contemporary clinical trials. Based on the article, it illustrates the research progress of the chemical ingredients, pharmacological actions, and clinical applications of Jiaotai Pills. With respect to the "five principles" of Q-marker in Chinese medicine, the Q-marker of Jiaotai Pills is comprehensively predicted and analyzed, noting that berberine, epiberberine, coptisine chloride, palmatine chloride, berberine chloride, berberrubine chloride, ferulic acid, cinnamic acid, cinnamaldehyde, proanthocyanidin B2 can be treated as the Q-marker of Jiaotai Pills. In addition, these components of Q-marker have been selected as indicators to provide a significant reference for the quality control and surveillance research of Jiaotai Pills.


Assuntos
Medicamentos de Ervas Chinesas , Biomarcadores , Controle de Qualidade
3.
World J Gastroenterol ; 26(19): 2349-2373, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32476798

RESUMO

BACKGROUND: Pancreatic cancer (PC) is one of the deadliest cancers worldwide. PC metastasis involves a complex set of events, including epithelial-mesenchymal transition (EMT), that increase tumor cell invasiveness. Recent evidence has shown that hypoxia is a major EMT regulator in pancreatic cancer cells and facilitates metastasis; however, the mechanisms remain elusive. AIM: To investigate the role of miR-301a in hypoxia-induced EMT in PC cells. METHODS: Real-time PCR and Western blot analysis were used to detect the expression of miR-301a and EMT markers in PDAC cells cultured in hypoxic and normoxic conditions. Western blot analysis was used to detect the expression of EMT markers in PDAC cells with miR-301a overexpression. Wound healing assay and Transwell assay were used to detect the migration capabilities of PDAC cells with miR-301a overexpression and knockout. Luciferase assay was used to detect the miR-301a promoter and the 3' untranslated region activity of TP63. Orthotopic PC mouse models were used to study the role of miR-301a in metastasis of PDAC cells in vivo. In situ hybridization assay was used to detect the expression of miR-301a in PDAC patient samples (adjacent paratumor and paired tumor tissues). . RESULTS: Hypoxic environment could directly promote the EMT of PC cells. The expression level of miR-301a was increased in a HIF2α dependent manner in hypoxia-cultured CFPAC-1 and BxPC-3 cells. Overexpression of miR-301a enhanced the hypoxia-induced EMT of PC cells, while knocking out miR-301a result in the suppression of hypoxia-induced EMT. TP63 was a direct target of miR-301a and involved in the metastatic process of PC cells. Furthermore, miR-301a upregulation facilitated PDAC distant metastasis and lymph node metastasis in vivo. Additionally, miR-301a overexpression was indicative of aggressive clinicopathological behaviors and poor prognosis. CONCLUSION: The newly identified HIF-2α-miR301a-TP63 signaling pathway may play a crucial role in hypoxia-induced EMT in PDAC cells.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinoma Ductal Pancreático/genética , MicroRNAs/genética , Neoplasias Pancreáticas/genética , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Regiões 3' não Traduzidas/genética , Animais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Hipóxia Celular/genética , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Inativação de Genes , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos , MicroRNAs/análise , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Pâncreas/patologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Regiões Promotoras Genéticas/genética , Transdução de Sinais/genética , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Zhongguo Zhong Yao Za Zhi ; 45(2): 383-390, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32237322

RESUMO

Enzyme-linked immunosorbent assay(ELISA) and metabolomics were used to analyze and compare two animal models of heart-kidney insomnia, in order to explore a more ideal animal model and preliminarily explore the essence of heart-kidney insomnia. Based on the clinical symptoms and disease characteristics of heart-kidney insomnia, the animal model of heart-kidney insomnia was reproduced through intraperitoneal injection with p-chlorophenylalanine(PCPA) and multi-factor interaction. The animal model of disease-syndrome combination was evaluated by behavioral observation, ELISA and metabolomics. Wistar rats were randomly divided into normal group, PCPA group and compound model group(FH). The rats' behavior, body weight, adrenal index and spleen index were recorded. The levels of corticotropin releasing hormone(CRH) and adrenocorticotropin(ACTH) in serum were detected by ELISA, and the differential metabolites in serum were detected by UPLC-QE-MS. The body weight and adrenal index in FH group were significantly lower than those in PCPA group(P<0.05); whereas ACTH and CRH in FH group were significantly higher than those in PCPA group by ELISA; nine potential biomarkers were identified by serum sample statistics. There were four main metabolic pathways in cardiorenal insomnia: pentose phosphate metabolism, alanine, aspartic acid and glutamic acid metabolism, histidine metabolism, and taurine and subtaurine metabolism. PCPA and multi-factor interaction method can successfully replicate the insomnia model, but multi-factor modeling method is more similar to clinical traditional Chinese medicine syndrome. Animal behavior, ELISA and metabolomics were used to evaluate the rat model of cardiorenal insomnia from in vitro to in vivo, from macro to micro, and from individual to the whole.


Assuntos
Modelos Animais de Doenças , Metaboloma , Soro/metabolismo , Distúrbios do Início e da Manutenção do Sono/metabolismo , Animais , Medicina Tradicional Chinesa , Ratos , Ratos Wistar
5.
Neurosci Bull ; 36(2): 153-164, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31444653

RESUMO

Fear memories are critical for survival. Nevertheless, over-generalization of these memories, depicted by a failure to distinguish threats from safe stimuli, is typical in stress-related disorders. Previous studies have supported a protective role of ketamine against stress-induced depressive behavior. However, the effect of ketamine on fear generalization remains unclear. In this study, we investigated the effects of ketamine on fear generalization in a fear-generalized mouse model. The mice were given a single sub-anesthetic dose of ketamine (30 mg/kg, i.p.) 1 h before, 1 week before, immediately after, or 22 h after fear conditioning. The behavioral measure of fear (indicated by freezing level) and synaptic protein expression in the basolateral amygdala (BLA) and inferior-limbic pre-frontal cortex (IL-PFC) of mice were examined. We found that only ketamine administered 22 h after fear conditioning significantly decreased the fear generalization, and the effect was dose-dependent and lasted for at least 2 weeks. The fear-generalized mice showed a lower level of brain-derived neurotrophic factor (BDNF) and a higher level of GluN2B protein in the BLA and IL-PFC, and this was reversed by a single administration of ketamine. Moreover, the GluN2B antagonist ifenprodil decreased the fear generalization when infused into the IL-PFC, but had no effect when infused into the BLA. Infusion of ANA-12 (an antagonist of the BDNF receptor TrkB) into the BLA or IL-PFC blocked the effect of ketamine on fear generalization. These findings support the conclusion that a single dose of ketamine administered 22 h after fear conditioning alleviates the fear memory generalization in mice and the GluN2B-related BDNF signaling pathway plays an important role in the alleviation of fear generalization.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Condicionamento Clássico/efeitos dos fármacos , Medo/efeitos dos fármacos , Ketamina/farmacologia , Receptores de N-Metil-D-Aspartato/metabolismo , Tonsila do Cerebelo/metabolismo , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Córtex Pré-Frontal/metabolismo , Transdução de Sinais/efeitos dos fármacos
6.
J Craniofac Surg ; 30(5): 1601-1604, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31299778

RESUMO

Facial anthropometric measurements play an important part not only in forensic cases but also in clinical treatments. The utilization of 2D photograph methods in facial anthropometric studies to found database with age, gender, ethnicity, and region was expanded by other races but little for Han nationality. This study was undertaken to describe reference ranges of facial anthropometric proportions of Han nationality and compare the anthropometric characteristics with other ethnicities. Our subjects focused on full-face photos of Han nationality in South China which consisted of 1176 healthy person (425 adult males, 421 adult females and 157 underage boys and 173 underage girls). Eight anthropometric landmarks on photos were examined by ImageJ software, and 7 anthropometric ratios were analyzed. The results indicated sex- and age- and ethnics-related anthropometric variations in Chinese Han nationality in South China. For adults, females have larger ratios in intercanthal-nasal width and lip height index and smaller nose width index; for impubes, boys were larger in lip height index and smaller in lip width ratios than girls, but as age achieved, the underage boys and girls exhibited a significantly larger nose width index and lip width index, smaller canthal index, intercanthal-nasal width and lip height index. Comparing with Japanese, India, North American and Persian, Chinese Han showed great difference in facial anthropometric proportions.


Assuntos
Antropometria , Antropometria/métodos , Grupo com Ancestrais do Continente Asiático , China/etnologia , Pálpebras/anatomia & histologia , Face/anatomia & histologia , Feminino , Humanos , Índia , Masculino , Valores de Referência
7.
Huan Jing Ke Xue ; 40(2): 987-993, 2019 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-30628368

RESUMO

The effects of biochar addition to compost on change characteristics and passivation effect of heavy metals (Cd, Pb, Cu, Zn, Ni) were investigated during the process of sludge composting with two different composts (group A:with biochar; group B:without biochar) and land application of compost. The results indicated that the total amount of heavy metals (except Ni) did not change significantly during the process of sludge composting and land application of compost. Additionally, biochar addition had little effect on the total amount of heavy metals. During the sludge composting process, five heavy metals (Cd, Pb, Cu, Zn, Ni) were passivated. Sludge composting with the addition of biochar can decrease the available contents of heavy metals, and the passivation effect of heavy metals was significant (P<0.05). The passivation rate of the five examined heavy metals (Cd, Pb, Cu, Zn, Ni)ranged from 16.39%-43.10%, and the passivation effect for Zn and Ni was more significant. However, the passivation effect was not significant in the sludge composting process without the addition of biochar (P>0.05). The concentrations of heavy metals in soil increased with the application of sewage sludge compost products. In the short term, biochar had a certain passivation effect on the available heavy metals in soils with sludge compost application, but the effect was not significant.


Assuntos
Carvão Vegetal , Compostagem , Metais Pesados/análise , Esgotos , Solo/química
8.
Chin J Nat Med ; 16(2): 113-124, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29455726

RESUMO

Due to ineffectiveness and side effects of existing analgesics, chronic pain has become one of the most complex and difficult problems in the clinic. Monoacylglycerol lipase (MAGL) is an essential hydrolase in the endocannabinoid system and has been identified as a potential target for the treatment of pain. In the present study, we designed and synthesized twelve tanshinone IIA analogs and screened their activity against MAGL. Selected compounds were tested for analgesic activity in vivo, with the acetic acid writhing test model. Among the test compounds, compound III-3 (IC50 120 nmol·L-1) showed significant activity against MAGL and ameliorated the clinical progression in the mouse pain model. Additionally, compound III-3, substitution with N-methyl-2-morpholinoacetamide, demonstrated improved solubility relative to tanshinone IIA.


Assuntos
Abietanos/administração & dosagem , Abietanos/síntese química , Analgésicos/administração & dosagem , Analgésicos/síntese química , Dor Crônica/tratamento farmacológico , Abietanos/química , Analgésicos/química , Animais , Dor Crônica/enzimologia , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Monoacilglicerol Lipases/antagonistas & inibidores , Monoacilglicerol Lipases/metabolismo , Relação Estrutura-Atividade
9.
Hum Gene Ther ; 29(2): 223-233, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29338433

RESUMO

Clustered regularly interspaced short palindromic repeats (CRISPR)-caspase 9 (Cas9) genome editing technology holds great promise for the field of human gene therapy. However, a lack of safe and effective delivery systems restricts its biomedical application. Here, a folate receptor-targeted liposome (F-LP) was used to deliver CRISPR plasmid DNA co-expressing Cas9 and single-guide RNA targeting the ovarian cancer-related DNA methyltransferase 1 (DNMT1) gene (gDNMT1). F-LP efficiently bound the gDNMT1 plasmid and formed a stable complex (F-LP/gDNMT1) that was safe for injection. F-LP/gDNMT1 effectively mutated endogenous DNMT1 in vitro, and then expressed the Cas9 endonuclease and downregulated DNMT1 in vivo. The tumor growth of both paclitaxel-sensitive and -resistant ovarian cancers were inhibited by F-LP/gDNMT1, which shows fewer adverse effects than paclitaxel injection. Therefore, CRISPR-Cas9-targeted DNMT1 manipulation may be a potential therapeutic regimen for ovarian cancer, and lipid-mediated delivery systems represent promising delivery vectors of CRISPR-Cas9 technology for precise genome editing therapeutics.


Assuntos
DNA (Citosina-5-)-Metiltransferase 1/genética , Técnicas de Transferência de Genes , Terapia Genética , Neoplasias Ovarianas/genética , Sistemas CRISPR-Cas/genética , Proliferação de Células/efeitos dos fármacos , DNA (Citosina-5-)-Metiltransferase 1/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Receptor 1 de Folato/genética , Receptor 1 de Folato/uso terapêutico , Edição de Genes , Regulação Neoplásica da Expressão Gênica , Humanos , Lipossomos/administração & dosagem , Lipossomos/química , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos
10.
Huan Jing Ke Xue ; 38(1): 405-411, 2017 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-29965073

RESUMO

Two different sludge composting products (with and without biochar) were applied in field to study the variations of total mercury (THg) and methylmercury (MeHg) in soil and plants,as well as their migration in the soil-plant system and accumulation ability in plants during the sludge compost land use process.The results indicated that the concentrations THg and MeHg in soil increased after applying sewage sludge compost products,while the THg level was still lower than the secondary standard of national soil environmental quality.Biochar was speculated to probably promote the soil mercury methylation with lower MeHg/THg ratios in different soil treatments.THg concentrations in mature plants were significantly lower than those in seedling stage,but MeHg levels were higher than those in seedling stage.An obvious influence of composting on MeHg enrichment in plants was observed,and this similar effect was not found for THg enrichment.MeHg concentration in the soils applied with biochar compost was significantly higher than that without applying biochar compost soil,while MeHg in plant presented a contrary trend with higher level observed in no-biochar compost soil,suggesting that the addition of biochar could be in favour of soil MeHg formation and inhibit the MeHg accumulation in plants by influencing its migration.Since a strong MeHg accumulation ability with BCF of 1.24-14.63 was present in plant,the mercury ecological risk in soil environment caused by long-term fertilizing should be noticed.


Assuntos
Mercúrio/análise , Compostos de Metilmercúrio/análise , Plantas/química , Esgotos/química , Poluentes do Solo/análise , Compostagem , Monitoramento Ambiental , Solo
11.
Huan Jing Ke Xue ; 38(4): 1647-1653, 2017 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-29965170

RESUMO

Effect of application of sewage sludge compost on the emission of greenhouse gas from soil was investigated by analyzing the dynamic characteristics and emission factor of CO2, CH4 and N2O in soil after spiking two different composts (A:compost with biochar, B:compost without biochar) with varying fertilizing amount into soil. The results indicated that emissions of CO2 and CH4 mainly occurred in the plant growth period with low fertilizer amount of biomass charcoal compost reducing CO2 emissions, and high application content increasing CO2 emissions. CH4 emission fluxes showed negative values, indicating that soil could adsorb CH4, and the adsorbing amount for control was significantly higher than those for other treatments (P<0.01). The absorbing amount in treatment A increased with the fertilizing amount (P<0.05). N2O emissions mainly occurred at the germination and seedling stages, and emission fluxes increased with the fertilizing amount (P<0.01). N2O was considered as the main generated greenhouse gas during agricultural process with sludge compost, and its emission factor from sludge compost soil was 1.02%-1.90% (A compost) and 1.28%-2.93% (B compost), respectively. Biochar could significantly reduce the carbon emission, as the total greenhouse gas released from soil with biochar compost was 19.49% to 35.56% less than that in soil without biochar, which was more obvious for N2O emission reduction (compared with CH4 mitigation).


Assuntos
Compostagem , Gases de Efeito Estufa/análise , Esgotos/química , Solo/química , Dióxido de Carbono/análise , Metano/análise , Óxido Nitroso/análise
12.
Huan Jing Ke Xue ; 38(10): 4390-4397, 2017 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-29965225

RESUMO

Effect of adding bamboo biochar into the compost at different dosages on greenhouse gas emissions was investigated by analyzing the dynamic characteristics of the process of municipal sludge composting with four different composts (S1:adding 2.5% bamboo biochar, S2:adding 5% bamboo biochar, S3:adding 10% bamboo biochar, CK:without bamboo biochar). The results showed that CH4 emissions mainly occurred during the heating period and the beginning of the altithermal period, accounting for 99.01%-99.81% of the total emissions. When the added bamboo biochar is less than 5%, CH4 emissions decrease with the increase in the amount of bamboo biochar. If it is more than 5%, CH4 emissions will clearly increase. CO2 emissions mainly occurred during the heating period and the altithermal period, accounting for 75.65%-86.58% of the total emissions. Adding bamboo biochar can reduce 3.37%-13.48% of the CO2 emissions but there is no significant difference between the treatments (P>0.05). N2O emissions mainly occurred during the heating period and the rotten period. Adding bamboo biochar can reduce the emissions of N2O; the more the amount of bamboo biochar, the less N2O emissions (P<0.05). The emission factors of CK, S1, S2, and S3 were 44.10, 37.57, 35.10, and 35.44 kg·t-1 of dry sludge, respectively. S1, S2, and S3 showed 14.81%-20.41% reduction in greenhouse gas emissions owing to the addition of bamboo biochar, indicating that bamboo biochar can reduce the carbon emissions in the process of sludge composting.


Assuntos
Carvão Vegetal , Compostagem , Gases de Efeito Estufa/análise , Esgotos , Dióxido de Carbono , Metano , Óxido Nitroso , Solo
13.
Oncotarget ; 7(32): 52207-52217, 2016 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-27438147

RESUMO

Interleukin-15 has been implicated as a promising cytokine for cancer immunotherapy, while folate receptor α (FRα) has been shown to be a potentially useful target for colon cancer therapy. Herein, we developed F-PLP/pIL15, a FRα-targeted lipoplex loading recombinant interleukin-15 plasmid (pIL15) and studied its antitumor effects in vivo using a CT26 colon cancer mouse model. Compared with control (normal saline) treatment, F-PLP/pIL15 significantly suppressed tumor growth in regard to tumor weight (P < 0.001) and reduced tumor nodule formation (P < 0.001). Moreover, when compared to other lipoplex-treated mice, F-PLP/pIL15-treated mice showed higher levels of IL15 secreted in the serum (P < 0.001) and ascites (P < 0.01). These results suggested that the targeted delivery of IL15 gene might be associated with its in vivo antitumor effects, which include inducing tumor cell apoptosis, inhibiting tumor proliferation and promoting the activation of immune cells such as T cells and natural killer cells. Furthermore, hematoxylin and eosin staining of vital organs following F-PLP/pIL15 treatment showed no detectable toxicity, thus indicating that intraperitoneal administration may be a viable route of delivery. Overall, these results suggest that F-PLP/pIL15 may serve as a potential targeting preparation for colon cancer therapy.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias do Colo , Sistemas de Liberação de Medicamentos/métodos , Receptor 1 de Folato/metabolismo , Terapia Genética/métodos , Interleucina-15/administração & dosagem , Animais , Linhagem Celular Tumoral , Lipossomos/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C
14.
Huan Jing Ke Xue ; 37(7): 2738-2744, 2016 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-29964486

RESUMO

Sludge composting is an efficient way to realize the reclamation of waste sludge, while the Green House Gas (GHG) accompanying with it has raised great concern worldwide. However, we do lack the primary data in this area and a great uncertainty of the effect and GHG emission characteristics of sludge composting process in low-temperature environment also exists. This study is aiming to investigate the emission characteristics of GHG from composting in low-temperature environment by applying two different bulking agents to dewatered urban sludge. The results showed that aerobic composting could go smoothly even in an environment with lower temperature, yet the maturity was low due to a sharp drop of pile temperature at the stage of maturing. Sawdust treatment could reduce the total nitrogen loss compared with cornstalk treatment, while its GHG emission equivalence was higher (169.45 and 133.13 kg·t-1 dry sludge, respectively). The accumulative CH4 emissions of sawdust and cornstalk were 0.648 and 0.689 kg·t-1 dry sludge, respectively, of which over 75% was from the first two weeks; total N2O emissions of sawdust and cornstalk were 0.486 and 0.365 kg·t-1 dry sludge, of which more than 90% came from the decomposting process. On the whole, because of the relatively short duration of high temperature as well as the low temperature during mature stage, the process had an especially low emission of CH4 but a relatively high discharge of N2O. For composting in low-temperature environment, necessary measures should be taken to control N2O emission in the late period in order to realize GHG reduction.


Assuntos
Compostagem , Gases de Efeito Estufa/análise , Esgotos/química , Nitrogênio , Estações do Ano
15.
J Biomed Nanotechnol ; 11(11): 2011-23, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26554159

RESUMO

The incidence and mortality rate of colorectal cancer increase every year, making it a serious threat to human health. Targeted immunogene therapy is a novel method of treating this type of cancer. Colon cancer overexpresses folate receptor α (FRα) and folate-modified liposomes for colon cancer immunogene therapy may suppress tumor growth effectively. In this study, F-PLP/pIL12, an FRα-targeted lipoplex loading plasmid interleukin-12 (pIL12) was prepared and its physicochemical properties were characterized. Then the antitumor effect of F-PLP/pIL12 was studied in an in vivo model of CT-26 colon cancer. F-PLP/pIL12 was associated with about 56.6% tumor growth inhibition compared with the saline control. The production of malignant ascites was significantly less pronounced than in controls, and there were fewer tumor nodules and less overall tumor mass (P < 0.01). There was more IL12 expression and IFN-γ secretion in F-PLP/pIL12-treated tumor tissues, but there was less FRα expression. The antitumor mechanisms involved inducing tumor cell apoptosis, reducing microvessel density, and stimulating TNF-α secretion. In addition, there were fewer M2 macrophages in the tumor microenvironment of tissues stimulated with F-PLP/pIL12, which also activated the natural killer cells. H&E staining of vital organs suggested that F-PLP/pIL12 is safe for use in intraperitoneally administered cancer therapy. It was here concluded that F-PLP/plL12 may be a suitable targeting formulation for colon cancer immunogene therapy.


Assuntos
Antineoplásicos/farmacocinética , Neoplasias do Colo/metabolismo , Ácido Fólico/farmacocinética , Terapia Genética/métodos , Imunoterapia/métodos , Interleucina-12/genética , Lipossomos/farmacocinética , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Citocinas/genética , Citocinas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Receptor 1 de Folato/genética , Receptor 1 de Folato/metabolismo , Ácido Fólico/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Lipossomos/química , Lipossomos/farmacologia , Camundongos
16.
J Hazard Mater ; 278: 592-6, 2014 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-25019577

RESUMO

Nanoscale zero-valent iron (nZVI) has been considered as an effective agent for reductive debromination of polybrominated diphenyl ethers (PBDEs). But the high lipophilicity of PBDEs will hinder their debromination owing to the inefficient contact of PBDEs with nZVI. In this study, different ionic forms of surfactants were investigated aiming to promote PBDE debromination, and the beneficial effects of surfactant were found to be: nonionic polyethylene glycol octylphenol ether (Triton X-100, TX)>cationic cetylpyridinium chloride (CPC)>anionic sodium dodecyl benzenesulfonate (SDDBS). Except for with SDDBS, the promotion effect for PBDE debromination was positively related to the surfactant concentrations until a critical micelle concentration (CMC). The debromination process of octa-BDE and its intermediates could be described as a consecutive reaction. The corresponding rate constants (k) for the debromination of parent octa-BDE (including nona- to hepta-BDEs), the intermediates hexa-, penta-, and tetra-BDEs are 1.24 × 10(-1) h(-1), 8.97 × 10(-2) h(-1), 6.50 × 10(-2) h(-1) and 2.37 × 10(-3) h(-1), respectively.


Assuntos
Bromo/química , Éteres Difenil Halogenados/química , Ferro/química , Tensoativos/química , Benzenossulfonatos/química , Cetilpiridínio/química , Cinética , Nanopartículas/química , Octoxinol/química , Oxirredução
17.
Huan Jing Ke Xue ; 35(3): 964-71, 2014 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-24881384

RESUMO

Nano-zerovalent iron (nZVI) approach is effective in the debromination of polybrominated biphenyl ethers (PBDEs). The kinetics and degradation pathway are the key issues to understand the PBDEs degradation mechanisms. In this study, nZVI, synthesized through liquid phase reduction method, coupled with Triton X-100, could completely debrominate the highly brominated congeners of a commercial octa-BDEs mixture within 46 h. The debromination of octa-BDEs could be described by means of pseudo-first-order kinetics with the reaction constant (k) of 0.106 h(-1). In case of lacking the PBDE standards, an effective approach has been developed to determine the unknown PBDE congeners using the quantitative-structure retention relationship (QSRR) model. The retention time of all 39 PBDE congeners in a standard mixture was firstly analyzed with gas chromatography coupled with an electron capture detector (GC-ECD), and the relative retention time (RRT) for each standard was obtained after normalizing the RT by the average RT of BDE47 and BDE183. Then a QSRR model was developed by fitting the RRT of each PBDE congener and its specific RRT index. The debromination products of octa-BDEs were identified using this QSRR model and the degradation pathway of octa-BDEs was elucidated. The results showed that in the stepwise reductive debromination process of PBDEs by nZVI, meta-debromin was facile to be degraded.


Assuntos
Água Doce/química , Éteres Difenil Halogenados/química , Ferro/química , Cromatografia Gasosa , Poluentes Ambientais/química , Halogenação , Cinética , Octoxinol , Relação Quantitativa Estrutura-Atividade
19.
Chemistry ; 17(33): 9180-7, 2011 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-21732435

RESUMO

Five iridium bis(carbene) complexes, [Ir(pmi)(2)(pypz)] (1), [Ir(mpmi)(2)(pypz)] (2), [Ir(fpmi)(2)(pypz)] (3), [Ir(fpmi)(2)(pyim)] (4), and [Ir(fpmi)(2)(tfpypz)] (5) (pmi=1-phenyl-3-methylimdazolin-2-ylidene-C,C(2'); fpmi=1-(4-fluorophenyl)-3-methylimdazolin-2-ylidene-C,C(2'); mpmi=1-(4-methyl-phenyl)-3-methylimdazolin-2-ylidene-C,C(2'); pypz=2-(1H-pyrazol-5-yl)pyridinato; pyim=2-(1H-imidazol-2-yl)pyridinato; and tfpypz=2-(3-(trifluoromethyl)-1H-pyrazol-5-yl)pyridinato), were synthesized and their structures were characterized by NMR spectroscopy, mass spectroscopy and X-ray diffraction. These complexes showed phosphorescent emission with the emission maxima between 453 and 490 nm. Various spectrophotometric measurements, cyclic voltammetric studies, and density functional theory (DFT) calculations show that, unlike most of the phosphorescent cyclometalated iridium complexes, the lowest unoccupied molecular orbital (LUMO) energy and the emissive state of these iridium complexes are mainly controlled by the N,N'-heteroaromatic (N^N) ligand. Despite the fact that the LUMO levels of these complexes are mainly on the N^N ligands, the efficiencies of the electroluminescent (EL) devices are very high. For example, the EL devices using [Ir(mpmi)(2)(pypz)], [Ir(fpmi)(2)(pypz)], and [Ir(fpmi)(2)(tfpypz)] as the dopant emitters exhibited light- to deep-blue electrophosphorescence with external quantum efficiencies of 15.2, 14.1, and 7.6% and Commission Internationale d'Énclairage (x,y) coordinates (CIE(x,y)) of (0.14, 0.27), (0.14, 0.18) and (0.14, 0.10), respectively.

20.
J Nat Prod ; 73(8): 1370-4, 2010 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-20669930

RESUMO

The effect of [6]-shogaol (1) on cytosolic free Ca(2+) concentrations ([Ca(2+)](i)) and viability has not been explored previously in oral epithelial cells. The present study has examined whether 1 alters [Ca(2+)](i) and viability in OC2 human oral cancer cells. Compound 1 at concentrations > or = 5 microM increased [Ca(2+)](i) in a concentration-dependent manner with a 50% effective concentration (EC(50)) value of 65 microM. The Ca(2+) signal was reduced substantially by removing extracellular Ca(2+). In a Ca(2+)-free medium, the 1-induced [Ca(2+)](i) elevation was mostly attenuated by depleting stored Ca(2+) with thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor). The [Ca(2+)](i) signal was inhibited by La(3+) but not by L-type Ca(2+) channel blockers. The elevation of [Ca(2+)](i) caused by 1 in a Ca(2+)-containing medium was not affected by modulation of protein kinase C activity, but was inhibited by 82% with the phospholipase A2 inhibitor aristolochic acid I (20 microM). U73122, a selective inhibitor of phospholipase C, abolished 1-induced [Ca(2+)](i) release. At concentrations of 5-100 microM, 1 killed cells in a concentration-dependent manner. These findings suggest that [6]-shogaol induces a significant rise in [Ca(2+)](i) in oral cancer OC2 cells by causing stored Ca(2+) release from the thapsigargin-sensitive endoplasmic reticulum pool in an inositol 1,4,5-trisphosphate-dependent manner and by inducing Ca(2+) influx via a phospholipase A2- and La(3+)-sensitive pathway.


Assuntos
Canais de Cálcio Tipo L/efeitos dos fármacos , Cálcio/análise , Catecóis/farmacologia , Catecóis/química , Linhagem Celular Tumoral , Citosol/metabolismo , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Estrenos/farmacologia , Humanos , Inositol 1,4,5-Trifosfato/metabolismo , Estrutura Molecular , Neoplasias Bucais , Inibidores de Fosfolipase A2 , Proteína Quinase C/efeitos dos fármacos , Proteína Quinase C/metabolismo , Pirrolidinonas/farmacologia , Tapsigargina/farmacologia
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