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1.
Biomed Pharmacother ; 123: 109755, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31926375

RESUMO

Skin toxicities induced by epidermal growth factor receptor inhibitors such as Erlotinib plagues clinical challenges. Chinese formulas have a unique advantage in reducing side effects. Here, we aim to investigate the skin protecting function of XiaoZhenFang (XZF), a clinical adjuvant prescription made up of Lonicerae Japonicae Flos, Lithospermum Erythrorhizon, Smilacis Glabrae Rhizoma, Forsythiae Fructus, Spirodelae Herba, Cortex Moutan and Prunellae Spica. Our data showed that XZF aqueous extract effectively reduced skin toxicities induced by Erlotinib in vivo using established mice model. Next, we used a systems pharmacology approach to investigate the pharmacological mechanism of XZF with the goal of understanding its effects at the system, organ, and molecular levels. 44 candidate compounds and 103 potential targets were identified by network pharmacology. Inflammation, cell stress and the EGFR-related signal pathways, which may participate in the skin protection afforded by XZF, were analyzed by gene enrichment. Importantly, our in vivo experimental results largely validated XZF's mechanism of action, as predicted by the system pharmacology analysis. Our study uncovered the effect and mechanism of XZF in attenuating skin toxicities induced by EGFRI, providing a basis for the development of in-hospital preparations and new drugs for the prevention of skin toxicities.

2.
Fish Shellfish Immunol ; 96: 152-160, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31794843

RESUMO

C-type lectins are Ca2+-dependent carbohydrate-binding proteins containing one or more carbohydrate-recognition domains (CRDs). C-type lectins play crucial roles in innate immunity, including nonself-recognition and pathogen elimination. In the present study, two C-type lectins (designated ReCTL-1 and ReCTL-2) were identified from the shrimp Rimicaris exoculata which dwells in deep-sea hydrothermal vents. The open reading frames of ReCTL-1 and ReCTL-2 encoded polypeptides of 171 and 166 amino acids respectively, which were both composed of a signal peptide and a single CRD. The key motifs determining the carbohydrate binding specificity of ReCTL-1 and ReCTL-2 were respectively Glu-Pro-Ala (EPA) and Gln-Pro-Asn (QPN), which were firstly discovered in R. exoculata. ReCTL-1 and ReCTL-2 displayed similar pathogen-associated molecular pattern (PAMP) binding features and they bound three PAMPs-ß-glucan, lipopolysaccharide and peptidoglycan-with relatively high affinity. In addition, both could efficiently recognize and bind Gram-positive bacteria, Gram-negative bacteria and fungi. However, ReCTL-1 and ReCTL-2 exhibited different microbial agglutination activities: ReCTL-1 agglutinated Staphylococcus aureus and Saccharomyces cerevisiae, while ReCTL-2 agglutinated Micrococcus luteus, Vibrio parahaemolyticus and V. fluvialis. Both ReCTL-1 and ReCTL-2 inhibited the growth of V. fluvialis. All these results illustrated that ReCTL-1 and ReCTL-2 could function as important pattern-recognition receptors with broad nonself-recognition spectra and be involved in immune defense against invaders, but their specificities are not the same. In addition, the two ReCTLs possessed different carbohydrate binding specificities from each other and from the classical pattern: ReCTL-1 with an EPA motif bound d-galactose and l-mannose, while ReCTL-2 with a QPN motif bound d-fucose and N-acetylglucosamine.

3.
Mol Pharm ; 16(12): 4826-4835, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31663764

RESUMO

Tumor-targeted ligand modification and nanosized coloaded drug delivery systems are promising for cancer therapy. In this study, we showed that coix seed oil and tripterine coloaded microemulsions with a transferrin modification (Tf-CT-MEs) could improve the treatment of cervical cancer. Tf-CT-MEs exhibited good stability in serum and a notably synergistic antiproliferation effect. In the HeLa xenograft tumor-bearing mouse model, Tf-CT-MEs accumulated at tumor sites and penetrated deeply in tumor tissues. Tf-CT-MEs had superior anticancer efficacy in vivo, which greatly slowed the growth of tumors (***p < 0.001 vs saline). We also found that Tf-CT-MEs inhibited tumor cell proliferation, enhanced antiangiogenesis, and induced apoptosis by regulating bax/bcl-2 and the activating caspase-3 pathway. Tf-CT-MEs decreased by 27.7, 26.9, 61.2, and 42.5% of concentrations of TGF-ß1, CCL2, TNF-α, and IL-6 in serum, respectively. In addition, Tf-CT-MEs showed little toxicity in vital organs. These results were due to the improved drug delivery efficiency. Collectively, Tf-CT-MEs enhance tumor-targeting, facilitate deep penetration of drugs, and have promising potential as an efficient treatment for cervical cancer.

4.
Environ Int ; 133(Pt B): 105191, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31639604

RESUMO

BACKGROUND: Perchlorate, nitrate, and thiocyanate are well-known thyroid disrupters and may contribute to changes in body weight. However, the associations between environmental exposure to these chemicals and obesity-related outcomes remain unclear. OBJECTIVES: We aim to examine the urinary levels of perchlorate, nitrate, and thiocyanate and their associations with obesity and abdominal obesity in the U.S. METHODS: Here, we investigated the data of 16,265 adults aged 20-85 years from the National Health and Nutritional Examination Survey (NHANES) in 2001-2014. Urinary levels of perchlorate, nitrate, and thiocyanate were measured by ion chromatography combined with electrospray tandem mass spectrometry. Obesity and abdominal obesity were defined by the body mass index and waist circumference, respectively. Logistic regression models were used to estimate the associations. RESULTS: Overall, 5794 (35.6%) cases of obesity and 9090 cases (55.9%) of abdominal obesity were observed among the participants. In multivariable-adjusted logistic regression models, urinary nitrate was inversely associated with obesity (p = 0.0022 for trend), while urinary thiocyanate was positively related to obesity (p < 0.001 for trend). Compared with the lowest quartile, the odds ratios with 95% confidence intervals (CIs) across increasing quartiles were 0.95 (95% CI, 0.83-1.08), 0.88 (0.75-1.03), and 0.74 (0.60-0.90) for urinary nitrate and 1.31 (1.16-1.48), 1.53 (1.36-1.73), and 1.73 (1.47-2.03) for urinary thiocyanate. Urinary perchlorate was not correlated with obesity. Similar associations were also found between exposure to these chemicals and abdominal obesity. CONCLUSIONS: A higher exposure to urinary nitrate was associated with a lower risk of obesity, while a positive association was observed for urinary thiocyanate. These findings emphasize the need to longitudinally evaluate environmental exposure to perchlorate, nitrate, and thiocyanate with respect to their effect on obesity in humans.

5.
J Immunol ; 203(7): 1845-1856, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31484728

RESUMO

The immune signaling pathway mediated by Dectin-1 is important in mammals to modulate the production of IL-17 and TNF-α. Recently, IL-17 and TNF have also been characterized in invertebrates to play crucial roles in antibacterial immune responses, although the immune recognition and regulation mechanisms to produce IL-17 and TNF are still not well investigated. In the current study, a novel C-type lectin receptor (named CgCLec-HTM) with a signal peptide, a carbohydrate recognition domain, a transmembrane domain, and a nonclassical ITAM (hemITAM) in the cytoplasmic tail was identified from oyster Crassostrea gigas CgCLec-HTM could bind LPS and various bacteria. After binding to its ligands, CgCLec-HTM was associated with the Src homology 2 (SH2) domain of spleen tyrosine kinase (CgSyk) by the hemITAM in its cytoplasmic tail to promote ERK (CgERK) phosphorylation. The activated CgERK could interact with CgRel to induce CgRel nuclear translocation. The CgRel in the nucleus eventually induced the transcription of CgIL-17s and CgTNF. The results demonstrated that CgCLec-HTM with a broad binding spectrum of bacteria could be associated with CgSyk to transfer immune signals into the intracellular ERK-Rel pathway to induce CgIL-17 and CgTNF production.

6.
Org Biomol Chem ; 17(18): 4621-4628, 2019 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-31017597

RESUMO

An efficient one-pot stepwise method to synthesize 3-styryl-4-arylcoumarins from simple alkynoates is demonstrated. On the basis of the control experiments, a possible mechanism involving light-driven radical cyclization and Pd-catalysed cross-coupling processes for this synthesis method is proposed. The results of X-ray analysis and spectroscopy experiments prove that the substituent effect has a significant influence on the absorption and emission properties of the synthesized 3-styryl coumarins.

7.
Environ Sci Technol ; 53(7): 3610-3619, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30835446

RESUMO

The application of tandem catalysis is rarely investigated in degrading organic pollutants in the environment. Herein, a tandem catalyst on single platinum (Pt) nanoparticles (Pt0 NPs) is prepared for the sequential degradation of formaldehyde (HCHO) to carbon dioxide gas [CO2(g)] at room temperature. The synthesis approach includes coating of uniform Pt NPs on SrBi2Ta2O9 platelets using a photoreduction process, followed by calcination of the sample in the atmosphere to tune partial transformation of Pt0 atoms to Pt2+ ions in the tandem catalyst. The conversion of HCHO to CO2(g) is monitored by in situ Fourier transform infrared spectroscopy, which shows first conversion of HCHO to CO32- ions onto Pt0 active sites and subsequently the conversion of CO32- ions to CO2(g) by neighboring Pt2+ species of the catalyst. The later process with Pt2+ species does not allow CO32- poisoning of the catalyst. The enhanced activity of the prepared tandem catalyst to oxidize HCHO is maintained continuously for 680 min. Comparatively, the catalyst without Pt2+ shows activity for only 40 min. Additionally, the tandem catalyst presented herein performs better than the Pt/titanium dioxide (TiO2) catalyst to degrade HCHO. Overall, the tandem catalyst may be applied to degrade organic pollutants efficiently.


Assuntos
Nanopartículas Metálicas , Platina , Catálise , Domínio Catalítico , Formaldeído , Oxirredução , Temperatura Ambiente
8.
Sci Total Environ ; 656: 1337-1345, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30625662

RESUMO

Acrylamide (AA), a ubiquitous chemical that is present in surrounding environment and baked or fried carbohydrate-rich food, has recently been linked to cardiac developmental toxicity. However, the toxicological role of AA exposure in the cardiac development remains largely unknown. Here we showed the cardiotoxicity of AA and its role in cardiomyocyte interactions in zebrafish embryos during ventricular morphogenesis. Using the embryo model of transgenic zebrafish Tg(Tp1:d2GFP;myl7:mCherry), we found AA interfered the dynamics of Notch signaling in the endocardium during early cardiogenesis. Prolonged exposure to AA thickened the chamber wall and prevented the trabeculae from extending into the lumen of ventricular chamber. As a result, AA reduced the ventricular shortening fraction and spatial dimension via excessively activating the Notch signal in myocardium during cardiac maturation. Moreover, exposure to AA inhibited the re-distribution of N­cadherin and failed to coordinate cardiomyocyte interactions between the myocardium layers due to the lack of delaminated cardiomyocytes. Therefore, AA-treated embryos exhibited subcellular pathological states including disarrayed myofibrils and abnormal morphology of mitochondria despite normal proliferation of cardiomyocytes. In addition, we found overexpression of some cardiac-specific transcription factors, such as hand2 and nkx2.5, in hearts of AA-treated embryos compared with those in control group. Our study provided the evidence that the period of ventricular chamber morphogenesis might be a vulnerable window in zebrafish, and revealed new insights into how AA might exert cardiac developmental toxicity.


Assuntos
Acrilamida/efeitos adversos , Desenvolvimento Embrionário/efeitos dos fármacos , Poluentes Ambientais/efeitos adversos , Morfogênese/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Peixe-Zebra/embriologia , Animais , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/embriologia , Transdução de Sinais/efeitos dos fármacos
9.
Fish Shellfish Immunol ; 84: 704-710, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30359751

RESUMO

Japanese eel (Anguilla japonica) has become a commercially important fish species all over the world. High-density aquaculture has led to congestion and contributed to bacterial infection outbreaks that have caused high mortality. Therefore a 56-days feeding trial was conducted to determine the effects of dietary Bacillus amyloliquefaciens (GB-9) and Yarrowia lipolytica lipase2 (YLL2) on growth performance, digestive enzymes activity, innate immunity and resistance to pathogens of A. japonica. Fish growth performance was significantly affected by dietary YLL2 supplementation but not by GB-9. Fish fed diets with YLL2 at 2.0 g/kg diet in combination of high and low levels of GB-9 (5.0 g/kg and 2.0 g/kg) produced the highest growth. For digestive enzyme, lipase and trypsin activities was promoted by dietary containing YLL2, while amylase activities was increased by dietary containing YLL2, GB-9 single or combination. For innate immunity, the mucus lysozyme activity, leukocytes phagocytosis activity and reactive oxygen species level of skin, peroxidase and lysozyme activity of serum were enhanced in fish fed with GB-9 compared to those in control group (p < 0.05). The highest resistance to Vibrio anguillarum and Aeromonas hydrophila was determined in fish fed with 5.0 g kg-1 GB-9 + 2.0 g/kg YLL2. This study demonstrated that GB-9 and YLL2 enhanced non-specific immune defense system of A. japonica, providing them with higher resistance to pathogens. The present results suggested that the combination of these supplements could be considered as potential biological additives for aquaculture farmed fish.


Assuntos
Anguilla/imunologia , Bacillus amyloliquefaciens/química , Hidrolases de Éster Carboxílico/administração & dosagem , Doenças dos Peixes/imunologia , Proteínas Fúngicas/administração & dosagem , Imunidade Inata/efeitos dos fármacos , Imunidade nas Mucosas/efeitos dos fármacos , Probióticos/farmacologia , Aeromonas hydrophila/fisiologia , Anguilla/crescimento & desenvolvimento , Anguilla/metabolismo , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Trato Gastrointestinal/enzimologia , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Distribuição Aleatória , Vibrio/fisiologia , Vibrioses/imunologia , Vibrioses/veterinária
10.
Dev Comp Immunol ; 91: 1-7, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30287242

RESUMO

Pattern recognition receptors (PRRs) are essential in recognizing specific pathogen-associated molecular patterns (PAMPs) on microbes and triggering responses to eliminate the invading pathogens. Previous genomic studies have revealed a great number of PRR genes in the Pacific oyster Crassostrea gigas, a sessile and filter-feeder marine bivalve belonging to the phylum Mollusca. On the survey of PRRs in the assembly oyster reference genome version 9, a total of 1084 PRRs were identified, which were composed of at least 12 gene families. Some of the gene families were significantly expanded, including C-type lectins (CTLs), fibrinogen-related proteins (FREPs), scavenger receptor cysteine-rich repeat protein (SRCRs), leucine-rich repeat (LRR)-only proteins (LRRops), and especially C1q domain-containing proteins (C1qDCs). The transcriptomic profiles of these abundant PRRs in response to PAMP treatments were investigated by RNA-Seq using the SOLiD EZ BeadTM system. Compared to the control library, there were 6,655, 7,273, 7,593, 6,830, 6687 and 8250 differentially expressed genes in the haemocytes of oysters in response to lipopolysaccharide (LPS) stimulation for 6 h, 12 h and 24 h, and peptidoglycan (PGN), glucan (GLU) and poly I:C (IC) stimulation for 12 h, respectively. After stimulation for 12 h, there were 134, 97, 114 and 159 genes up-regulated in the LPS, PGN, GLU and IC library, respectively. Most of the gene families involved in immune response towards PAMPs were C1qDCs, CTLs and FREPs, while only a few members of LRR and immunoglobin-containing proteins (LRRIGs), retinoic acid-inducible gene I [RIG-I]-like receptors (RLRs) and Toll like receptors (TLRs) were up-regulated. After LPS stimulation, the expression level of 258 non-redundant PRR genes in oyster haemocytes increased significantly with different expression pattern, and most of them were C1qDCs, CTLs, LRRops and FREPs. The transcriptomic analyses indicated that there was a dynamic and orchestrated specific expression regulation of numerous PRR genes in response to pathogen invasion. The expanded PRR gene family members were differentiated with more specific functional responses to certain PAMPs rather than the versatile ones. Based on the different expression pattern during the LPS stimulation, the oyster PRRs could be assigned into three consecutive steps in the response against pathogen invading. All the results would provide useful information for future studies of oyster PRRs and deep insight into the researches on invertebrate innate immunity.


Assuntos
Crassostrea/imunologia , Hemócitos/fisiologia , Receptores de Reconhecimento de Padrão/genética , Transcriptoma/genética , Animais , Clonagem Molecular , Complemento C1q/genética , Fibrinogênio/genética , Perfilação da Expressão Gênica , Interações Hospedeiro-Patógeno , Imunidade Inata , Lectinas Tipo C/genética , Lipopolissacarídeos/imunologia , Estrutura Molecular , Padrões Moleculares Associados a Patógenos/imunologia , Análise de Sequência de RNA , Receptores Toll-Like/metabolismo
11.
Clin Nutr ; 38(4): 1936-1944, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30025746

RESUMO

BACKGROUND & AIMS: Government has popularized potatoes as the staple food in China. Potatoes as a potassium-rich food show high glycemic responses after consumption. Whether potato consumption is prospectively linked with the risk of hypertension remains unclear in oriental populations. In this study, we aimed to investigate the association of potato consumption with the risk of hypertension among Chinese people. METHODS: A total of 11,763 adults (≥20 years old) who were free of hypertension at baseline were enrolled from China Health and Nutrition Survey (CHNS) Cohort study in 1989-2011. Participants were excluded if they were <20 years old, identified to be pregnant, and previously diagnosed with hypertension, cancers, infarction, apoplexy and diabetes at baseline. Cox proportional hazards regression models were used to estimate the associations after adjusting for potential confounders. RESULTS: During average 11.3 years of follow-up, 4033 incident cases of hypertension were ascertained. People who consumed more amounts of total potatoes, stir-fried potatoes, and non stir-fried potatoes had higher risk of hypertension (P for trend = 0.1225, 0.2168 and 0.0456, respectively). Multivariable hazard ratios (HRs) for increased consumption of total potatoes were 1.402 (95% confidence interval [CI], 1.270-1.548), 1.198 (95% CI, 1.014-1.415), and 1.120 (95% CI, 0.929-1.349) compared with non-consumers. However, the participants with higher intake of potato consumption were inclined to have lower risk of hypertension when excluding the non-consumers of total potatoes or stir-fried potatoes (P for trend = 0.0271 and 0.0001). In addition, a positive association of sweet potatoes intake with hypertension risk was only found in urban residents (P for trend = 0.0239). CONCLUSIONS: Our results showed that potato consumption was prospectively associated with hypertension in Chinese population. As the urbanization process continues along with the transition to Western-style diets, more consideration should be taken before the formulation of potato popularization is promoted in China.

12.
Int J Pediatr Otorhinolaryngol ; 117: 163-166, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30579073

RESUMO

OBJECTIVE: In this study, we aimed to characterize the significant DNA methylation module of seasonal allergic rhinitis. METHODS: Methylation profiling E-GEOD-50222 was obtained from ArrayExpress database. Differential co-methylation network (DCN) was constructed based on the methylation data. From the DCN, we characterized multiple differential modules (M-DMs). Significant module was mapped to pathways to identify significant enriched pathways. RESULTS: At the criteria of absolute Pearson coefficient value > 0.8, the edges were chose to construct DCN. In the DCN, 16 seed genes were identified. Seed genes were used to construct M-DMs. After statistical analysis, one significant module with p < 0.05 were obtained. After pathways enrichment analysis, 17 significant pathways with p < 0.05 were obtained, and most of these pathways were associated with DNA replication. CONCLUSION: One multiple differential module was identified in SAR, and seventeen significant pathways mapped by the module were identified as important factors in SAR. These results may provide new insights into the molecular mechanism of DNA methylation in SAR.


Assuntos
Metilação de DNA , Rinite Alérgica Sazonal/genética , Bases de Dados Genéticas , Redes Reguladoras de Genes , Humanos
13.
Biomater Sci ; 6(12): 3284-3299, 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30346001

RESUMO

A codelivery system that sequentially releases its contents is an effective strategy to enhance anticancer efficacy. Here, we fabricated multicomponent-based liposomes (T/CM-L) loaded with sodium tanshinone IIA sulfonate (STS) and a small-sized microemulsion of celastrol (CM), which shows synergistic anti-breast cancer activity through the initial release of STS for modulation of the tumor microenvironment, and subsequent release of CM (and its payloads) for eradication of tumor tissues. In vitro studies exhibited that T/CM-L induced massive apoptosis of MCF-7 cells, indicating a coordinated cytotoxicity against cancer cells. Once the liposomes had accumulated at the tumor site, STS was released from T/CM-L in the first place to repair abnormal vessels as well as to decrease the level of fibroblasts. Owing to the barriers of the microemulsion and the liposomes, the celastrol was then unloaded at a moderate rate to kill the tumor cells, which resulted in the shrinkage of the tumor size. Furthermore, T/CM-L displayed diminished systemic toxicity compared to celastrol used alone. Our work offers a novel strategy for combination anticancer treatment and holds promising potential not only for breast cancer treatment, but also for the treatment of other solid tumors.


Assuntos
Antineoplásicos/administração & dosagem , Liberação Controlada de Fármacos , Lipossomos/química , Neoplasias Mamárias Experimentais/tratamento farmacológico , Fenantrenos/administração & dosagem , Triterpenos/administração & dosagem , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Sinergismo Farmacológico , Feminino , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fenantrenos/farmacocinética , Fenantrenos/uso terapêutico , Triterpenos/farmacocinética , Triterpenos/uso terapêutico
14.
Drug Deliv ; 25(1): 1802-1810, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30343605

RESUMO

The aim of this study is to explore the influence of Ganoderma lucidum-derived polysaccharides (GLP) to coix oil-based microemulsion on pharmaceutical performance and anti-lung cancer treatment. GLP-integrated coix oil-based microemulsion (MEs(PS-GLP)) exhibited a clear spherical shape, small particle size, and good hydrodynamics similar to the coix oil-based microemulsion, but showed a lower zeta potential and a better stability. Fluorescence resonance energy transfer analysis presented that GLP was integrated with microemulsion as a single system. Notably, the average molecular distance between polysaccharide and microemulsion was approximately 1.7 nm. The half-maximal inhibitory concentration of MEs(PS-GLP) against A549 cells was about 119 µg/mL. In vivo imaging studies showed that introduction of GLP promoted the tumor-specific accumulation of microemulsion in comparison with controls. In vivo, antitumor results showed that MEs(PS-GLP) markedly inhibited the tumor growth of A549-bearing xenograft nude mice and obviously improve the serum immune index. Collectively, this study demonstrates the potential mechanism of spatial relation between polysaccharides and microemulsion and validates the significances of GLP on tumoral accumulation and antitumor efficacy.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/química , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Coix/química , Neoplasias Pulmonares/tratamento farmacológico , Óleos Vegetais/administração & dosagem , Óleos Vegetais/química , Polissacarídeos/farmacologia , Reishi/química , Células A549 , Animais , Antineoplásicos/farmacocinética , Antineoplásicos Fitogênicos/farmacologia , Composição de Medicamentos , Estabilidade de Medicamentos , Emulsões , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Óleos Vegetais/farmacologia , Polissacarídeos/química , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
15.
BMC Anesthesiol ; 18(1): 103, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-30086709

RESUMO

BACKGROUND: Dexmedetomidine (DEX), a highly sensitive α2-adrenoceptor agonist that possesses anxiolytic, sedative, and analgesic effects, has been documented as a preventative and treatment for emergence agitation (EA). The therapeutic should be given as a loading dose that is infused during a 10 min period, but if a rapid bolus injection is deemed to be hemodynamically appropriate, it would be a more opportune route of administration. So we studied the efficacy of different doses of DEX as a rapid bolus for children to prevent and treat EA. METHODS: One hundred patients were enrolled and randomly divided into five groups: the control group (group D1), the 0.25 µg/kg DEX group (group D2), the 0.5 µg/kg DEX group (group D3), the 0.75 µg/kg DEX group (group D4), and the 1 µg/kg DEX group (group D5). Heart rate (HR), mean blood pressure (MBP) and blood oxygen saturation (SaO2) were recorded immediately before the study drug injection (baseline) and every minute for 5 min thereafter and at the time points of the skin cut and hernial sac pull. EA and pain were assessed in the post -anesthesia care unit, and any complementary medicine and adverse events were recorded too. RESULTS: The incidence of EA was significantly decreased in group D4 and group D5 compared with D1.All groups exhibited similar baseline HR and MBP. After administered, HR and MBP were significantly decreased in all DEX group compared with group D1.In groups D3, D4 and D5, the minimal HR was decreased significantly compared with the groups D1 and duration time of minimal HR significantly prolonged in group D5, but no patient needed treatment. As the dosage increased, the recovery time was significantly prolonged. There were no significant differences in occurrence time of minimal HR, the incidence of complementary medicine and adverse events among groups. CONCLUSION: Rapid intravenous injection (IV) bolus administration of 0.75 and 1.0 µg/kg of DEX could improve the recovery profile by reducing the incidence of EA in children. Although its use resulted in a transient decreases in HR and MBP, DEX was clinically well-tolerated in children. TRIAL REGISTRATION: No. ChiCTR-IPR-17010658 . Registered 17 February 2017.


Assuntos
Dexmedetomidina/uso terapêutico , Delírio do Despertar/tratamento farmacológico , Delírio do Despertar/prevenção & controle , Criança , Pré-Escolar , Dexmedetomidina/administração & dosagem , Dexmedetomidina/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/uso terapêutico , Injeções Intravenosas , Masculino , Medição da Dor/efeitos dos fármacos , Estudos Prospectivos , Fatores de Tempo
16.
Fish Shellfish Immunol ; 82: 250-257, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30125703

RESUMO

A 12-weeks feeding trial was performed to investigate the possible effects of supplementation of Hybrid sturgeon diet with Bacillus amyloliquefaciens (GB-9) and Yarrowia lipolytica lipase2 (YLL2) single or combined on immune response and growth performance of Hybrid sturgeon (Acipenser schrenkii ♂and Acipenser baeri ♀). For this aim, Hybrid sturgeons were fed with four experimental diets namely: Diet 1 (0-control), Diet 2 (5.0 g/kg GB-9), Diet 3 (4.0 g/kg YLL2), and Diet 4 (5.0 g/kg GB-9 + 4.0 g/kg YLL2), respectively. After fed with varied diets, growth performance, mucosal immune response, leukocytes immune response and serum immunological response were measured. The results indicated that supplementations of GB-9 + YLL2 resulted in a significant increase in final weight, Docosahexaenoic acid (DHA) and Eicosapentenoic acid (EPA) concentration, compared with that of control (p < 0.05). For innate immunity, the results showed that skin mucus lysozyme activity, leukocytes phagocytosis activity and reactive oxygen species level, and serum alternative complement pathway activity, peroxidase and lysozyme activity were significantly higher in supplemented groups compared to the control (p < 0.05). The highest values were recorded in fish fed both YLL2 and GB-9 with respect to the individual application. The present results suggested that the combination of these supplementation could be considered as potential feed-additives for aquaculture farmed fish.


Assuntos
Bacillus amyloliquefaciens/química , Hidrolases de Éster Carboxílico/administração & dosagem , Peixes/crescimento & desenvolvimento , Peixes/imunologia , Proteínas Fúngicas/administração & dosagem , Probióticos/farmacologia , Ração Animal/análise , Animais , Cruzamento , Dieta/veterinária , Suplementos Nutricionais/análise , Imunidade Inata/efeitos dos fármacos , Imunidade nas Mucosas/efeitos dos fármacos , Distribuição Aleatória
17.
Environ Int ; 119: 37-46, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29933236

RESUMO

BACKGROUND: Perfluoroalkyl chemicals (PFCs) as possible cardiovascular disrupters are universally detected in humans. However, evidence from epidemiological studies appears insufficient and ambiguous. OBJECTIVES: We aim to examine the serum PFCs levels and their associations with the prevalence of cardiovascular diseases (CVD) and related outcomes in general US population. METHODS: We investigated the serum levels of 12 major PFCs, including perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), 2-(N-ethyl-perfluorooctane sulfonamido) acetate (EPAH), 2-(N-methyl-perfluorooctane sulfonamido) acetate (MPAH), perfluorodecanoic acid (PFDE), perfluorobutane sulfonate (PFBS), perfluoroheptanoic acid (PFHP), perfluorononanoic acid (PFNA), perfluorooctane sulfonamide (PFSA), perfluoroundecanoic acid (PFUA), and perfluorododecanoic acid (PFDO), in 10,859 participants from the National Health and Nutritional Examination Survey (NHANES) 1999-2014. Logistic regression models were used to estimate the associations between serum PFCs and 5 self-reported CVD outcomes, including congestive heart failure, coronary heart disease, angina pectoris, heart attack, and stroke. Linear regression analyses were used to estimate the PFCs and their associations with 8 traditional CVD risk factors like serum triglyceride and total cholesterol. RESULTS: In multivariable-adjusted models, total PFCs were positively associated with total CVD (p for trend = 0.0166), independent of traditional CVD risk factors, such as smoking status, diabetes, hypertension and serum cholesterol level. Compared with reference quartile of total PFCs levels, the multivariable adjusted odds ratios in increasing quartiles were 1.23 [95% confidence interval (CI): 0.91-1.66], 1.47 (95% CI: 1.14-1.89) and 1.45 (95% CI: 1.06-1.98) for total CVD. Similar positive associations were found if considering individual PFCs including PFOS, PFUA, MPAH, EPAH, PFDO, PFSA and PFBS. In addition, serum levels of MPAH and PFDO were positively associated with congestive heart failure; PFNA, PFDE, and PFUA were positively associated with coronary heart disease; PFUA and PFDO were positively associated with angina pectoris; and PFNA was positively associated with heart attack. CONCLUSIONS: Our findings suggested that exposure to PFCs was positively associated with risk of CVD. Further longitudinal studies are needed to increase our understanding about the role of PFCs exposure in the prevalence of CVD.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Fluorcarbonetos/sangue , Humanos , Razão de Chances , Fatores de Risco
18.
Environ Int ; 117: 154-163, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29753146

RESUMO

BACKGROUND: Long-term exposure to acrylamide (AA) from diet sources may induce oxidative stress and chronic inflammation. However, the association between AA exposure and the prevalence of cardiovascular diseases (CVD) remains unclear. OBJECTIVES: We aimed to examine the association between blood exposure levels of AA biomarkers and the prevalence of main types of CVD in a general population of US adults. METHODS: We analyzed the associations between AA hemoglobin biomarkers [hemoglobin adducts of acrylamide (HbAA) and glycidamide (HbGA), sum of HbAA and HbGA (HbAA+HbGA), and ratio of HbGA to HbAA (HbGA:HbAA)] and self-reported diagnosis of CVD in 8290 adults (≥20 years of age) from the National Health and Nutrition Examination Survey (NHANES) 2003-2006. Multivariable logistic regression models were employed for estimating the associations in three groups classified by the combination of smoking status and serum cotinine levels. RESULTS: In people exposed to environmental tobacco smoke (n = 4670), HbGA, HbAA+HbGA, and HbGA:HbAA were significantly and inversely associated with the prevalence of total CVD (p < 0.0001, p = 0.0155, and p = 0.0014 for trend, respectively) after adjusting for various covariates. The odd ratios (ORs) for total CVD in the highest quartiles of HbGA, HbAA+HbGA, and HbGA:HbAA were 0.311 [95% confidence interval (CI): 0.193-0.500], 0.664 (95% CI: 0.485-0.911), and 0.495 (95% CI: 0.326-0.752) when compared with the individual lowest quartiles. In active smokers (n = 2432), HbAA was positively associated with CVD risk (p = 0.0088 for trend), while HbGA:HbAA was inversely related to total CVD (p = 0.0137 for trend). However, no significant associations of any AA hemoglobin biomarker with total and individual CVD prevalence were observed in the nonsmoking group (n = 1188). CONCLUSIONS: AA hemoglobin biomarkers are significantly associated with CVD in the active smoking group and the group exposed to environmental tobacco smoke but not in the nonsmoking group. Further prospective studies should clarify the causal relationship between HbAA and HbGA and the prevalence of CVD.


Assuntos
Acrilamida/toxicidade , Doenças Cardiovasculares/epidemiologia , Exposição Ambiental/análise , Adulto , Humanos , Inquéritos Nutricionais , Adulto Jovem
19.
Oncol Lett ; 15(5): 6329-6335, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29731848

RESUMO

Solamargine, an active ingredient of Solanum nigrum, has been previously revealed to inhibit the proliferation of cancer cells. However, the effect of solamargine on human cholangiocarcinoma cells and the underlying molecular mechanism remain unknown. In the present study, the molecular mechanism underlying the anti-cancer effect of solamargine was assessed in human cholangiocarcinoma QBC939 cells. The results of the present study revealed that solamargine inhibited the viability of QBC939 cells in a dose-dependent manner. Furthermore, solamargine significantly induced the apoptosis of QBC939 cells and altered the mitochondrial membrane potential of cells. Quantitative polymerase chain reaction analysis revealed that solamargine decreased the mRNA level of B-cell lymphoma-2 (Bcl-2), Bcl-extra-large and X-linked inhibitor of apoptosis protein but increased the mRNA level of Bcl-2-associated X protein (Bax). In addition, western blot analysis demonstrated that solamargine inhibited the protein expression of Bcl-2 and poly ADP ribose polymerase (PARP), and promoted the protein expression of Bax, cleaved PARP, caspase 3, cleaved caspase 3 and caspase 7. Therefore, the results of the present study revealed that solamargine may induce apoptosis via the mitochondrial pathway and alter the level of apoptosis-associated proteins in human cholangiocarcinoma QBC939 cells. This in vitro study demonstrated that solamargine may be an effective chemotherapeutic agent against cholangiocarcinoma in clinical practice.

20.
Fish Shellfish Immunol ; 78: 238-247, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29678793

RESUMO

Galectins are ß-galactoside binding lectins that play crucial roles in innate immunity in vertebrates and invertebrates through their conserved carbohydrate-recognition domains (CRDs). In the present study, single- and four-CRD-containing galectins were identified in oyster Crassostrea gigas (designated CgGal-2 and CgGal-3). The open reading frames (ORFs) of CgGal-2 and CgGal-3 encode polypeptides of 200 and 555 amino acids, respectively. All CRDs of CgGal-3 include two consensus motifs essential for ligand-binding, and a novel motif is present in CgGal-2. Pathogen-associated molecular pattern (PAMP) profiles were determined for recombinant rCgGal-2 and rCgGal-3, and rCgGal-2 displayed low binding affinity for PAMPs, while rCgGal-3 bound various PAMPs including glucan, lipopolysaccharide (LPS), and peptidoglycan (PGN) with relatively high affinity. Furthermore, rCgGal-2 and rCgGal-3 exhibited different microbe binding profiles; rCgGal-2 bound to Gram-negative bacteria (Escherichia coli and Vibrio vulnificus) and fungi (Saccharomyces cerevisiae and Pichia pastoris), while rCgGal-3 bound to these microbes but also to Gram-positive bacteria (Micrococcus luteus). In addition, rCgGal-3 possessed microbial agglutinating activity and coagulation activity against fungi and erythrocytes, respectively, but rCgGal-2 lacked any agglutinating activity. Carbohydrate binding specificity analysis showed that rCgGal-3 specifically bound D-galactose. Furthermore, rCgGal-2 and rCgGal-3 functioned as opsonin participating in the clearance against invaders in C. gigas. Thus, CgGal-2 with one CRD and CgGal-3 with four CRDs are new members of the galectin family involved in immune responses against bacterial infection. Differences in the organisation and amino acid sequences of CRDs may affect their specificity and affinity for nonself substances.


Assuntos
Crassostrea/genética , Galectina 2/genética , Galectina 3/genética , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Sequência de Aminoácidos , Animais , Crassostrea/imunologia , Fungos/fisiologia , Galectina 2/química , Galectina 2/imunologia , Galectina 3/química , Galectina 3/imunologia , Perfilação da Expressão Gênica , Bactérias Gram-Negativas/fisiologia , Bactérias Gram-Positivas/fisiologia , Filogenia , Alinhamento de Sequência
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