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1.
ACS Chem Neurosci ; 15(9): 1937-1947, 2024 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-38630556

RESUMO

The development of antiepileptic drugs is still a long process. In this study, heparin-modified superparamagnetic iron oxide nanoparticles (UFH-SPIONs) were prepared, and their antiepileptic effect and underlying mechanism were investigated. UFH-SPIONs are stable, homogeneous nanosystems with antioxidant enzyme activity that are able to cross the blood-brain barrier (BBB) and enriched in hippocampal epileptogenic foci. The pretreatment with UFH-SPIONs effectively prolonged the onset of seizures and reduced seizure severity after lithium/pilocarpine (LP)-induced seizures in rats. The pretreatment with UFH-SPIONs significantly decreased the expression of inflammatory factors in hippocampal tissues, including IL-6, IL-1ß, and TNF-α. LP-induced oxidative stress in hippocampal tissues was in turn reduced upon pretreatment with UFH-SPIONs, as evidenced by an increase in the levels of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) and a decrease in the level of lipid peroxidation (MDA). Moreover, the LP-induced upregulation of apoptotic cells was decreased upon pretreatment with UFH-SPIONs. Together, these observations suggest that the pretreatment with UFH-SPIONs ameliorates LP-induced seizures and downregulates the inflammatory response and oxidative stress, which exerts neuronal protection during epilepsy.


Assuntos
Epilepsia do Lobo Temporal , Heparina , Inflamação , Cloreto de Lítio , Nanopartículas Magnéticas de Óxido de Ferro , Estresse Oxidativo , Pilocarpina , Animais , Estresse Oxidativo/efeitos dos fármacos , Ratos , Masculino , Epilepsia do Lobo Temporal/induzido quimicamente , Epilepsia do Lobo Temporal/metabolismo , Epilepsia do Lobo Temporal/tratamento farmacológico , Cloreto de Lítio/farmacologia , Heparina/farmacologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/induzido quimicamente , Ratos Sprague-Dawley , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Anticonvulsivantes/farmacologia
3.
Mater Today Bio ; 25: 100996, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38420143

RESUMO

Reactive Oxygen Species (ROS) refers to a highly reactive class of oxidizing species that have the potential to induce cellular apoptosis and necrosis. Cuproptosis, a type of cell death, is primarily associated with the effects of copper ions. However, the specific relationship between ROS, cuproptosis, and osteosarcoma (OS) remains relatively unexplored. Additionally, there is limited research on the use of cuproptosis in conjunction with oxidative stress for treating OS and inhibiting tumor-induced bone destruction. To address these gaps, a novel treatment approach has been developed for OS and neoplastic bone destruction. This approach involves the utilization of glutathione (GSH) and pH-responsive organic-inorganic mesoporous silica nanoparticles@Cu2S@oxidized Dextran (short for MCD). The MCD material demonstrates excellent cytocompatibility, osteogenesis, tumor suppression, and the ability to inhibit osteoclast formation. The specific mechanism of action involves the mitochondria of the MCD material inhibiting key proteins in the tricarboxylic acid (TCA) cycle. Simultaneously, the generation of ROS promotes this inhibition and leads to alterations in cellular energy metabolism. Moreover, the MCD biomaterial exhibits promising mild-temperature photothermal therapy in the second near-infrared (NIR-II) range, effectively mitigating tumor growth and OS-induced bone destruction in vivo.

4.
J Clin Endocrinol Metab ; 108(12): 3239-3249, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37310344

RESUMO

CONTEXT: Although cognitive impairment in nonalcoholic fatty liver disease (NAFLD) has received attention in recent years, little is known about detailed cognitive functions in histologically diagnosed individuals. OBJECTIVE: This study aimed to investigate the association of liver pathological changes with cognitive features and further explore the underlying brain manifestations. METHODS AND PATIENTS: We performed a cross-sectional study in 320 subjects who underwent liver biopsy. Among the enrolled participants, 225 underwent assessments of global cognition and cognitive subdomains. Furthermore, 70 individuals received functional magnetic resonance imaging scans for neuroimaging evaluations. The associations among liver histological features, brain alterations, and cognitive functions were evaluated using structural equation model. RESULTS: Compared with controls, patients with NAFLD had poorer immediate memory and delayed memory. Severe liver steatosis (odds ratio, 2.189; 95% CI, 1.020-4.699) and ballooning (OR, 3.655; 95% CI, 1.419-9.414) were related to a higher proportion of memory impairment. Structural magnetic resonance imaging showed that patients with nonalcoholic steatohepatitis exhibited volume loss in left hippocampus and its subregions of subiculum and presubiculum. Task-based magnetic resonance imaging showed that patients with nonalcoholic steatohepatitis had decreased left hippocampal activation. Path analysis demonstrated that higher NAFLD activity scores were associated with lower subiculum volume and reduced hippocampal activation, and such hippocampal damage contributed to lower delayed memory scores. CONCLUSIONS: We are the first to report the presence and severity of NAFLD to be associated with an increased risk of memory impairment and hippocampal structural and functional abnormalities. These findings stress the significance of early cognitive evaluation in patients with NAFLD.


Assuntos
Disfunção Cognitiva , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/patologia , Estudos Transversais , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Hipocampo/diagnóstico por imagem , Hipocampo/patologia
5.
BMC Immunol ; 23(1): 39, 2022 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-35965334

RESUMO

OBJECTIVE: This study was designed to investigate the role of the nucleotide-binding-domain -and leucine-rich repeat -containing (NLR) family, pyrin-domain-containing 3 (NLRP3) inflammasome in the pathogenesis of polymyositis (PM). METHODS: Immunochemistry was performed to analyze the NLRP3, caspase-1 and interleukin-1 beta (IL-1ß) expression in the muscle tissue of PM patients. Rat model of PM and C2C12 cell were used to investigate the potential role of NLRP3 inflammasome in PM. RESULTS: The percentage of CD 68+ macrophages, and the expression levels of NLRP3, caspase-1 and IL-1ß in the muscle tissue were elevated in 27 PM patients. LPS/ATP treatment resulted in activation of NLRP3 inflammasome and secretion of IL-1ß as well as interferons (IFNs) and monocyte chemotactic protein-1 (MCP-1) in the Raw 264.7 macrophages. Meanwhile, LPS/ATP challenged activation of NLRP3 inflammasome induced overexpression of major histocompatibility complex class I (MHC-I), a key molecular of PM in the co-cultured C2C12 cells. The effect was decreased by treatment of NLRP3 inflammasome inhibitor MCC950 or siRNA of NLRP3 inflammasome. These findings suggested certain levels of IL-1ß rather than IFNs up-regulated MHC-I expression in C2C12 cells. IL-1ß blockade using neutralizing IL-1ß monoclonal antibody or siRNA of IL-1ß suppressed MHC-I overexpression. In vivo, NLRP3 inflammasome inhibition by MCC950 reduced the expression of NLRP3, IL-1ß and MHC-I in the muscle tissue of PM modal rats. Also, it attenuated the intensity of muscle inflammation as well as the CRP, CK, and LDH levels in the serum. CONCLUSION: NLRP3/caspase-1/IL-1ß axis may play an important role in the development of PM. Inhibition of NLRP3 activation may hold promise in the treatment of PM.


Assuntos
Inflamassomos , Polimiosite , Trifosfato de Adenosina , Animais , Caspase 1/genética , Caspase 1/metabolismo , Inflamassomos/metabolismo , Lipopolissacarídeos , Complexo Principal de Histocompatibilidade , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Polimiosite/genética , RNA Interferente Pequeno , Ratos , Regulação para Cima
6.
Front Immunol ; 13: 938439, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35812418

RESUMO

Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer, which is relatively resistant to anti-programmed cell death-1 (α-PD1) therapy, characterized as non-immunogenic, dense stroma and accumulation of M2 tumor-associated macrophages (TAMs). Despite progress in strategies to deplete extracellular matrix (ECM) and enhance tumor-cell immunogenicity, the combinatorial anti-cancer effects with α-PD1 need to be explored. Here, we applied doxorubicin hydrochloride liposome (Dox-L) as immunogenic cell death (ICD)-inducing nano-chemotherapy and used losartan as stroma-depleting agent to improve α-PD1 efficacy (Losartan + Dox-L + α-PD1). The results showed that losartan could cause ECM reduction, facilitating enhanced delivery of Dox-L and further dendritic cell (DC) maturation. Additionally, losartan could also alleviate hypoxia for TNBC, thus reprogramming pro-cancer M2 TAMs to anti-cancer M1 TAMs, successfully overcoming immune-suppressive microenvironment. These modifications led to a significant increase in T cells' infiltration and augmented anti-tumor immunity as exemplified by the notable reduction in tumor size and lung metastases. In summary, our findings support that combined treatment of losartan with Dox-L normalizes immunological-cold microenvironment, improves immuno-stimulation and optimizes the efficacy of TNBC immunotherapy. A novel combinational strategy with FDA-approved compounds proposed by the study may potentially be useful in TNBC clinical treatment.


Assuntos
Neoplasias de Mama Triplo Negativas , Animais , Linhagem Celular Tumoral , Humanos , Imunoterapia/métodos , Losartan/farmacologia , Losartan/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Microambiente Tumoral
7.
Chemosphere ; 303(Pt 2): 135058, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35642855

RESUMO

Straw will degrade into segment, powder and crystalline cellulose, while the agricultural film will degrade into microplastics (MPs) in farmland soils. The specific surface area of these micro-particles increases and many new functional groups are formed in the degradation process, which can be a good vector of pesticides. To more accurately and truly analyze the risk of main imported substances and their degradation products against pollutants in soil, the adsorption behavior and mechanism of four commonly used pesticides on aged polyethylene microplastics (APE), wheat straw segment (WSS), wheat straw powder (WSP), and straw crystalline cellulose (SCC) were analyzed and compared through batch adsorption experiments and infrared spectrum. The adsorption kinetics of four pesticides on MPs and straw degradation products tended to be pseudo-second-order kinetics; the adsorption isotherms of pesticides on APE and SCC tended to fit the Freundlich model, while on WSP and WSS tended to fit the Langmuir model. The adsorption was a spontaneous endothermic increase process, suggesting that the main adsorption force of pesticides on MPs and straw degradation products was hydrophobic diffusion. The adsorption of pesticides against WSP and WSS still had a certain π-π conjugation and electrostatic interaction. And the adsorption amount on the straw degradation products followed the order of WSP > WSS > APE > SCC, presumably related to the specific surface area and pore volume of the adsorbent. As WSP, WSS could adsorb more pesticides, the straw returning to the field can be used for slow-release of pesticides to reduce the dosage of pesticides.


Assuntos
Praguicidas , Poluentes Químicos da Água , Adsorção , Celulose , Cinética , Microplásticos , Praguicidas/química , Plásticos/química , Pós , Solo , Triticum , Poluentes Químicos da Água/análise
9.
Eur J Nucl Med Mol Imaging ; 49(5): 1560-1573, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34746970

RESUMO

BACKGROUND: PET imaging has been widely used in diagnosis of neurological disorders; however, its application to pediatric population is limited due to lacking pediatric age-specific PET template. This study aims to develop a pediatric age-specific PET template (PAPT) and conduct a pilot study of epileptogenic focus localization in pediatric epilepsy. METHODS: We recruited 130 pediatric patients with epilepsy and 102 age-matched controls who underwent 18F-FDG PET examination. High-resolution PAPT was developed by an iterative nonlinear registration-averaging optimization approach for two age ranges: 6-10 years (n = 17) and 11-18 years (n = 50), respectively. Spatial normalization to the PAPT was evaluated by registration similarities of 35 validation controls, followed by estimation of potential registration biases. In a pilot study, epileptogenic focus was localized by PAPT-based voxel-wise statistical analysis, compared with multi-disciplinary team (MDT) diagnosis, and validated by follow-up of patients who underwent epilepsy surgery. Furthermore, epileptogenic focus localization results were compared among three templates (PAPT, conventional adult template, and a previously reported pediatric linear template). RESULTS: Spatial normalization to the PAPT significantly improved registration similarities (P < 0.001), and nearly eliminated regions of potential biases (< 2% of whole brain volume). The PAPT-based epileptogenic focus localization achieved a substantial agreement with MDT diagnosis (Kappa = 0.757), significantly outperforming localization based on the adult template (Kappa = 0.496) and linear template (Kappa = 0.569) (P < 0.05). The PAPT-based localization achieved the highest detection rate (89.2%) and accuracy (80.0%). In postsurgical seizure-free patients (n = 40), the PAPT-based localization also achieved a substantial agreement with resection areas (Kappa = 0.743), and the highest detection rate (95%) and accuracy (80.0%). CONCLUSION: The PAPT can significantly improve spatial normalization and epileptogenic focus localization in pediatric epilepsy. Future pediatric neuroimaging studies can also benefit from the unbiased spatial normalization by PAPT. TRIAL REGISTRATION: NCT04725162: https://clinicaltrials.gov/ct2/show/NCT04725162.


Assuntos
Epilepsia , Fluordesoxiglucose F18 , Adulto , Fatores Etários , Criança , Epilepsia/diagnóstico por imagem , Epilepsia/cirurgia , Humanos , Imageamento por Ressonância Magnética , Projetos Piloto , Tomografia por Emissão de Pósitrons/métodos
10.
J AOAC Int ; 104(2): 479-484, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-33956983

RESUMO

BACKGROUND: Solanesol is an important pharmaceutical intermediate raw material, mainly used to synthesize coenzyme Q10, vitamin K2. It can be found prominent in potato stems and leaves. But now potato stems and leaves are always abandoned or discarded as they are not suitable for use as feed in aquaculture or other purposes. These agricultural waste resources can be reutilized as the corresponding extracts. OBJECTIVE: To develop a simple and standardized method for the detection of total solanesol in potato leaves and its extracts. METHODS: N-hexane was chosen as the extraction solvent for three times in the solanesol extraction from potato leaves. HPLC-MS was used for the detection. RESULTS: The LOQ was 0.3 µg/g and the linear range was from 0.1 to 50 µg/mL. The precision and stability were evaluated by the relative standard deviations (RSDs) of three samples (potato leaves, Extract-1, Extract-2) for interday and intraday. The accuracy of the method was evaluated by the recoveries of three different spiked concentrations of solanesol for three samples, and results showed it ranged from 80.7% to 99.0% with RSDs less than 8.7%. CONCLUSIONS: The method we established can provide a simple and standardized way for the extraction and detection of total solanesol. HIGHLIGHTS: The work laid a foundation for the resource reutilization of potato stem and leaf.


Assuntos
Solanum tuberosum , Cromatografia Líquida de Alta Pressão , Extratos Vegetais , Folhas de Planta , Terpenos , Nicotiana
11.
Ecotoxicol Environ Saf ; 209: 111781, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33340954

RESUMO

Compared with pristine agricultural polyethylene (PE) soil films microplastics (MPs), aged agricultural polyethylene (APE) soil films MPs have a rougher surface, more cracks and have some oxygen-containing functional groups that makes them adsorb organic pollutants, such as pesticides more easily. This may be more harmful to human beings than marine MPs as the agricultural soil films are closer to our living environment. But few works focused on the adsorption of pesticides on pristine or aged agricultural polyethylene soil films MPs. In order to promote the risk assessment of co-exposure of pesticides and agricultural polyethylene soil films MPs, a comparative study on the adsorption behavior and mechanism of four pesticides (carbendazim, diflubenzuron, malathion, difenoconazole) by pristine PE MPs and APE MPs were carried out in this paper. The results showed microcracks and surface oxidation observed on APE MPs. The adsorption kinetics and isotherm models indicated that the adsorption capacity of APE MPs was higher than that of PE MPs, which attribute to the larger surface area of APE MPs. The adsorption capacities of pesticides on APE MPs were positively correlated with LogKow (Water octanol partition coefficient) values of these four pesticides, showed the hydrophobic partitioning played the most important part in the adsorption, but also some H-bonding between secondary amines in the molecular of diflubenzuron and polar O-containing functional groups on APE MPs may be formed. And electrostatic forces or interactions are not the determining factor for these pesticides adsorption behavior of PE MPs, and the effect of pH is mainly driven by changes in sorbate properties rather than changes in surface properties of MPs. The results presented herein show the APE MPs can be a better vector of most hydrophobic pesticides than pristine MPs in the agricultural field, and more attention should be paid to the problem of films and pesticides residue in farmland soil.


Assuntos
Agricultura , Microplásticos/química , Praguicidas/química , Polietileno/química , Poluentes do Solo/química , Adsorção , Dioxolanos , Poluentes Ambientais , Humanos , Interações Hidrofóbicas e Hidrofílicas , Cinética , Plásticos/química , Solo/química , Triazóis , Água
12.
Front Endocrinol (Lausanne) ; 12: 789909, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35027910

RESUMO

Background: The efficacy of Kuntai capsule combined with letrozole (LE) in improving ovarian function of polycystic ovary syndrome (PCOS) has been evaluated before, but there is still a lack of evidence-based support for the regulation of sex hormone levels. In recent years, new randomized clinical trials (RCTs) have been reported on the effect of combined therapy on regulating sex hormone levels. Objective: We aimed to systematically evaluate the efficacy of Kuntai capsule combined with LE in the treatment of PCOS. Methods: A search across the China Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang database, PubMed, Web of Science, The Cochrane Library, and Embase was conducted on Kuntai capsule combined with LE in the treatment of PCOS. The time of the self-built database was up to April 30, 2021. RCTs of LE in the control group and LE combined with Kuntai capsule in the experimental group were selected. RevMan5.3 software was used for data analysis. Results: A total of 17 studies were gathered, which included 1,684 patients. The meta-analysis results showed that the total effective rate of the combined group was 93.36% and that of the LE group was 78.15%. The improvement in the ovulation rate, pregnancy rate, number of mature follicles, endometrial thickness, cervical mucus score, and serum follicle stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) in the combined group was consistent with the results of a previous meta-analysis and was better than that in the LE group (p < 0.05). In addition, the combination group was better than the LE group in regulating the levels of estradiol (E2) and testosterone (T) (p < 0.05). There were no adverse drug reactions in the two groups during treatment. Conclusion: As a type of pure traditional Chinese medicine preparation, Kuntai capsule combined with LE had a better effect than LE alone in the treatment of PCOS, with advantages mainly reflected in enhancing ovarian function and regulating the levels of sex hormones in vivo, among others, but the value of combined therapy still needs to be verified by more high-quality RCTs.


Assuntos
Inibidores da Aromatase/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Hormônios Gonadais , Letrozol/administração & dosagem , Ovário/efeitos dos fármacos , Síndrome do Ovário Policístico/tratamento farmacológico , Quimioterapia Combinada , Feminino , Hormônios Gonadais/sangue , Humanos , Testes de Função Ovariana/métodos , Ovário/fisiologia , Ovulação/efeitos dos fármacos , Ovulação/fisiologia , Síndrome do Ovário Policístico/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos
13.
Food Chem ; 321: 126657, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32244135

RESUMO

Tea polyphenols, chlorophyll and lutein generally cause strong matrix effects and challenge analysis of trace substances in tea. Seven frequently used adsorbents were chosen to test removal ability for tea polyphenols, chlorophyll and lutein based on the adsorption isotherm fitting. Results showed that MWCNTs-NH2 demonstrated the strongest removal ability, which may be ascribed to the π-π and electrostatic interaction. Then a method of MWCNTs-NH2 modified QuEChERS coupled with HPLC-MS/MS detection of 10 organophosphorus pesticide residues in tea was developed and validated. Unlike traditional QuEChERS, only one adsorbent (MWCNTs-NH2) was applied in this method to replace the combined effect of various adsorbents, which improved the easiness and generality of the method. The LOQs were 1.7-9.0 µg/kg. The average recovery rate ranged from 72% to 116% with RSDs less than 14%. This study provides a targeted strategy to develop analysis method for trace substances in a complicated matrix.


Assuntos
Organofosfatos/química , Resíduos de Praguicidas/química , Chá/química , Adsorção , Cromatografia Líquida de Alta Pressão , Organofosfatos/análise , Resíduos de Praguicidas/análise , Espectrometria de Massas em Tandem
14.
Clin Nucl Med ; 45(1): 57-59, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31693617

RESUMO

Primary hepatic angiosarcoma was diagnosed in a 59-year-old woman who presented an arthralgia of limbs and dry cough for 6 weeks. Physical examination revealed digital clubbing. A Tc-MDP bone scintigraphy showed diffusely increased uptake along the cortical margins of long bones, suggesting hypertrophic osteoarthropathy.


Assuntos
Hemangiossarcoma/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Osteoartropatia Hipertrófica Secundária/diagnóstico por imagem , Feminino , Hemangiossarcoma/complicações , Humanos , Neoplasias Hepáticas/complicações , Pessoa de Meia-Idade , Osteoartropatia Hipertrófica Secundária/complicações , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Medronato de Tecnécio Tc 99m
15.
Chemosphere ; 244: 125491, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31835051

RESUMO

Polyethylene (PE) agricultural soil films are easily embrittled and decomposed to microplastics (MPs) in environment. As widely used pesticides in vegetable farmland, carbendazim, dipterex, diflubenzuron, malathion, difenoconazole have potential environmental and human safety risks. They are often coexisting with MPs in the environment, and may cause consequential pollution to the ecosystem. Studying the adsorption behavior between pesticides and PE agricultural soil films MPs would be helpful for the risk assessment of co-exposure of pesticides and MPs. Herein, a systematic study on batch adsorption experiments was performed to determine the adsorption process of pesticides on MPs, the environmental factors on adsorption capacity were evaluated, and the adsorption mechanisms were discussed. Results suggested that all these five pesticides can adsorb on MPs, especially for diflubenzuron and difenoconazole. The adsorption kinetics and isotherm fitted to the Pseudo-second-order and Freundlich model, respectively, indicating that besides the adsorption onto surface sites, mass transfer and intraparticle diffusion were involved in the adsorption process, and the adsorption process was mostly controlled by physical and chemical interactions. The adsorption amounts of 5 pesticides on PE MPs follow the order of DIF > DIFE > MAL > CAR > DIP with KF correlated positively with octanol-water partition coefficients (LogKow). The thermodynamic study indicates the adsorption of all pesticides as spontaneous and exothermic processes. The results of this study illustrated that PE MPs can be a good carrier of pesticides in agricultural field.


Assuntos
Microplásticos/química , Praguicidas/química , Poluentes do Solo/química , Adsorção , Agricultura , Difusão , Dioxolanos , Ecossistema , Cinética , Plásticos , Polietileno/química , Solo , Triazóis
16.
Biomed Pharmacother ; 118: 109383, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545251

RESUMO

Given studies have shown that Artemisinin (ART) reduces cancer cell proliferation, migration, invasion, tumorigenesis and metastasis. In this study, we evaluated the roles of ART in clear cell renal cell carcinoma (ccRCC) progression. We measured the eff ;ects of ART on cancer cell proliferation, colony formation, migration, invasion and tumorigenesis. CCK-8 assay demonstrated that ART inhibited cell growth with IC50 values 31.30 ±â€¯0.73 µM in UMRC-2 and 23.97 ±â€¯0.92 µM in CAKI-2, respectively. Colony formation assay shown that ART inhibited cell colony formation. Transwell migration and invasion assay shown that ART inhibited RCC migration and invasion. Realtime-qPCR assay shown that ART decreased the mRNA levels of proliferation related genes c-Myc, cyclin D1 and PCNA, and reduced the mRNA levels of mesenchymal genes N-cadherin, Vimentin and Snail, but increased the mRNA levels of epithelial marker E-cadherin. Moreover, ART inhibited AKT signaling pathway. In the presence of AKT inhibitor VIII, a pan-AKT inhibitor, ART reduced more cell proliferation, migration and invasion than in the absence of AKT inhibitor VIII, suggesting combination of ART and AKT inhibitor enhanced the anti-cancer effects of ART. Furthermore, the in vivo xenograft tumor model results suggested that ART decreased tumor size and weight, and suppressed AKT signaling. Taken together, our results indicated that ART inhibited ccRCC cell proliferation, colony formation, migration, invasion and tumorigenesis. Combination of ART and AKT inhibitor enhanced the anti-cancer cell proliferation, migration and invasion.


Assuntos
Antineoplásicos/uso terapêutico , Artemisininas/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Animais , Antineoplásicos/farmacologia , Artemisininas/química , Artemisininas/farmacologia , Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias Renais/patologia , Masculino , Camundongos Nus , Invasividade Neoplásica , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ensaio Tumoral de Célula-Tronco
17.
Contrast Media Mol Imaging ; 2018: 3417190, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30510493

RESUMO

Objective: To explore the diagnostic value of maximum standard uptake value (SUVmax) from 18F-FDG PET/CT images in enlarged mediastinal lymph nodes of unknown etiology. Methods: We performed a retrospective study of patients with enlarged mediastinal lymph nodes on 18F-FDG PET/CT scans. SUVmax and the short axis and long axis of lymph nodes were recorded. These parameters were compared among the five commonest causes of mediastinal lymphadenopathy: lymphoma, metastatic disease, sarcoidosis, tuberculosis, and lymphadenitis. Histopathologic diagnosis was recorded as the final golden standard. Results: A total of 94 patients (62 men and 32 women; age range 7-85 y) were included with final diagnoses of 42 patients with benign pathology and 52 patients with malignancies. The sensitivity, specificity, and the accuracy of PET/CT in diagnosis of the benign and malignant mediastinal lymph nodes were 94.2%, 73.8%, and 85.1%, respectively. The SUVmax of benign and malignant groups were 13.10 ± 5.21 and 12.59 ± 5.50, respectively, which had no statistical difference (P > 0.05). However, the long axis and the short axis of lymph nodes in the benign and malignant groups were 2.86 ± 1.02 cm, 1.77 ± 0.60 cm and 6.04 ± 3.83 cm, 3.95 ± 2.08 cm, respectively (P < 0.05). The diagnostic values of PET/CT were higher than those of the long or short axis. However, the specificity of PET/CT was lower (73.8%) than that from the long or short axis (90.5% and 92.9%, respectively), although no statistical difference existed. Among the five common causes of mediastinal lymphadenopathy, significant differences could be seen in SUVmax and in the long axis and the short axis of lymph nodes (P < 0.05). Conclusions: SUVmax, a commonly used semiquantitative measurement, was not helpful for differentiation between benign and malignant lesions in patients with enlarged mediastinal lymph nodes in this study. Many benign lesions, such as sarcoidosis and tuberculosis, had high FDG uptake, possibly a trend that the size of the lymph nodes seems to have some diagnostic value.


Assuntos
Fluordesoxiglucose F18/farmacocinética , Linfonodos/diagnóstico por imagem , Mediastino/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Diagnóstico Diferencial , Feminino , Glicólise , Humanos , Linfonodos/metabolismo , Linfonodos/patologia , Masculino , Mediastino/diagnóstico por imagem , Pessoa de Meia-Idade , Projetos Piloto , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Curva ROC , Estudos Retrospectivos , Adulto Jovem
18.
Huan Jing Ke Xue ; 39(2): 916-926, 2018 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-29964858

RESUMO

This study selected Guiyu Town, Guangdong Province as the research area, the content of 15 kinds of metals (As, Be, Cd, Co, Cr, Cu, Hg, Li, Mn, Ni, Sb, Sn, Pb, V, and Zn) in the soil was determined, and the content of heavy metals (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn in the rice of this research area was identified. Multivariate statistical analysis and a human health risk assessment model were used to investigate the distribution characteristics and health risk of heavy metals in a soil-rice system. The results showed that Hg, Sb, and Sn in the surface soil surrounding the electronic waste dismantling area have obvious accumulation effect. The average content of Cd and Hg exceeds the Ⅱ standard limit of the "Environmental Quality Standard for Soil" (GB 156182-1995), and that Guiyu Town is more seriously polluted than Chendian Town and Simapu Town. The multivariate statistical analysis showed that Cu, Sb, Ni, Zn, Sn, Pb, and Hg originated from the surrounding electronic waste dismantling activities, Cd and Be originated from other man-made sources of pollution, and V, Li, Cr, Co, As, and Mn originated from natural sources. Heavy metal evaluation concentration in the soil-rice system by heavy metal migration accumulated in rice are in compliance with national food hygiene standards, and the enrichment ability is Cd > Zn > Cu > Ni > As > Cr > Hg > Pb. Soil heavy metal health risk assessment results showed that children are more susceptible to heavy metal pollution, and handling-oral ingestion is the main way of soil exposure risk. The non-carcinogenic risk and carcinogenic risk of heavy metals in the soil of each town are acceptable. The health risk in Guiyu Town through ingestion of rice is mainly from the elements that include As, Cr, Cu, and Ni.


Assuntos
Resíduo Eletrônico , Metais Pesados/análise , Oryza , Poluentes do Solo/análise , Criança , China , Monitoramento Ambiental , Humanos , Medição de Risco , Solo
19.
Huan Jing Ke Xue ; 39(1): 89-98, 2018 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-29965669

RESUMO

In order to investigate the distribution characteristics and the human health risks of 12 metals in drinking water sources from the Luhun Reservoir, Al, As, Cd, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, and Zn concentrations in 46 water samples collected from the reservoir in 2016 were measured and analyzed. The health risks caused by metals were assessed by using a human health risk assessment model. The results showed that the maximum concentration of Al (200.27 µg·L-1) and all concentrations of Mo (151.42-170.69 µg·L-1) in drinking water from the Luhun Reservoir exceeded the Environmental Quality Standards for Surface Water (GB 3838-2002) and Standards for Drinking Water Quality (GB 5749-2006) by 4.35% and 100%, respectively. A distinct spatial heterogeneity was found in the metal distribution, and the region with the highest metals concentrations was located southwest (upstream) and northeast (downstream) of the reservoir. The results of a health risk assessment indicated that children had greater health risks than adults. The health risks for metals through drinking were all higher than the values caused by dermal contact. Carcinogenic risks caused by Cr and As exceeded the maximum allowance levels (5×10-5 a-1) by 100% and 3.80%, respectively, and Cr accounted for 85% of the total carcinogenic risks. The non-carcinogenic risks of the metals (10-12-10-7 a-1) decreased in the order of Al > Mo > Cu > Pb > Ni > Hg > Fe > Zn > Mn, which had levels two to seven orders of magnitude lower than the maximum allowance levels.


Assuntos
Água Potável/análise , Metais Pesados/análise , Medição de Risco , Poluentes Químicos da Água/análise , Adulto , Criança , China , Monitoramento Ambiental , Humanos
20.
Huan Jing Ke Xue ; 38(3): 993-1001, 2017 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-29965569

RESUMO

To investigate the distribution characteristics and the human health risks of heavy metals in surface water samples, 30 samples were collected around electroplating factories of Machong, Shatian, Humen, Changan and Dalingshan towns in Dongguan city, 8 heavy metals(As, Cd, Cr, Cu, Hg, Ni, Pb and Zn) contents were measured and analyzed by using multivariate statistical analysis method and human health risk assessment model. The results showed that the maximum concentrations of Cr, Pb and the average concentration of Hg exceeded Environmental Quality Standards for Surface Water(GB 3838-2002, Grade Ⅲ), the concentrations of Cr, Cu, Hg, Ni, Zn and Pb during rainy season were all higher than that those during dry season. Multivariate statistical analysis indicated that Cd, Cr, Cu, Ni and Zn mainly originated from the contaminated electroplating factories, Pb and Hg were mainly affected by the traffic sources, and As was significantly correlated with natural sources. Health risk assessment result of surface water indicated that heavy metal pollution would lead to high health risks especially for children, and the health risks of heavy metals through drinking pathway were 2-3 orders of magnitude higher than the values caused by dermal contact pathway. Moreover, carcinogenic risks caused by Cr and As were higher than the maximum allowance levels (5×10-5 a-1), and non-carcinogenic risks of the heavy metals (10-10-10-7 a-1) decreased in the order of Pb > Ni > Cu > Hg > Zn, which were 4-5 orders of magnitude lower than the maximum allowance levels.


Assuntos
Galvanoplastia , Monitoramento Ambiental , Metais Pesados/análise , Poluentes Químicos da Água/análise , Criança , China , Cidades , Água Potável , Exposição Ambiental/análise , Humanos , Medição de Risco , Água
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