Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 24
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
2.
Expert Rev Clin Pharmacol ; 14(6): 761-771, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33835879

RESUMO

OBJECTIVES: Despite therapeutic vancomycin is regularly monitored, its dose requirements vary considerably between individuals. Various innovative vancomycin dosing strategies have been developed for dose optimization; however, the utilization of individual factors and extensibility is insufficient. We aimed to develop an optimal dosing algorithm for vancomycin based on the high-dimensional data using the proposed variable engineering and machine-learning methods. METHODS: This study proposed a variable engineering process that automatically generates second-order variable interactions. We performed an initial examination of independent variables and interactive variables using eXtreme Gradient Boosting. The vancomycin dose prediction model was established based on the derived variables. RESULTS: Based on the evaluation of the model performance in the validation cohort, our algorithm accounted for 67.5% of variations in the vancomycin doses. Subgroup analysis showed better performance in patients with medium and high body weight (with the ideal predictive percentage of 72.7% and 73.7%), and low and medium levels of serum creatinine (with the ideal predictive percentage of 77.8% and 73.1%) than in other groups. CONCLUSION: The new vancomycin dose prediction model is potentially useful for patients whose population profiles are similar to those of our patients and yielded desired reference of clinical indicators with specific breakpoints.


Assuntos
Antibacterianos/administração & dosagem , Aprendizado de Máquina , Modelos Biológicos , Vancomicina/administração & dosagem , Idoso , Algoritmos , Estudos de Coortes , Creatinina/sangue , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
3.
Drug Des Devel Ther ; 15: 1549-1559, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33883878

RESUMO

Purpose: This study aimed to establish an optimal model to predict vancomycin trough concentrations by using machine learning. Patients and Methods: We enrolled 407 pediatric patients (age < 18 years) who received vancomycin intravenously and underwent therapeutic drug monitoring from June 2013 to April 2020 at Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine. The median (interquartile range) age and weight of the patients were 2 (0.63-5) years and 12 (7.8-19) kg. Vancomycin trough concentrations were considered as the target variable, and eight different algorithms were used for predictive performance comparison. The whole dataset (407 cases) was divided into training group and testing group at the ratio of 80%: 20%, which were 325 and 82 cases, respectively. Results: Ultimately, five algorithms (XGBoost, GBRT, Bagging, ExtraTree and decision tree) with high R 2 (0.657, 0.514, 0.468, 0.425 and 0.450, respectively) were selected and further ensembled to establish the final model and achieve an optimal result. For missing data, through filling the missing values and model ensemble, we obtained R 2 =0.614, MAE=3.32, MSE=24.39, RMSE=4.94 and a prediction accuracy of 51.22% (predicted trough concentration within ±30% of the actual trough concentration). In comparison with the pharmacokinetic models (R 2 =0.3), the machine learning model works better in model fitting and has better prediction accuracy. Conclusion: Therefore, the ensemble model is useful for the vancomycin concentration prediction, especially in the population of children with great individual variation. As machine learning methods evolve, the clinical value of the ensemble model will be demonstrated in the clinical practice.

4.
Rheumatol Ther ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33666893

RESUMO

INTRODUCTION: The objective of this study is to identify the potential risk factors for progression from subclinical to clinical psoriatic arthritis (PsA). METHODS: A retrospective, longitudinal, case-control study was conducted at a single hospital, including 25 patients with clinically confirmed PsA in the case group and 137 controls without confirmed PsA. All patients in both groups had a medical history of subclinical PsA. Various baseline covariates were collected from all patients when they had a status of subclinical PsA. Univariate, multivariate, stratified, and interaction analyses were employed to identify potential risk factors of transiting to clinical PsA from subclinical PsA. RESULTS: In multivariate logistic regression analysis, older age (OR 10.15, 95% CI 2.79-36.91, p = 0.00), alcohol drinking (OR 3.43, 95% CI 1.17-10.12, p = 0.03), elevated high-sensitivity C-reactive protein (hs-CRP) (OR 1.05, 95% CI 1.01-1.09, p = 0.03) were identified as risk factors for transition from subclinical to clinical PsA. Stratified and logistic regression analyses suggest a significant interaction between age and fatty liver. For patients aged less than 45 years old, the association between fatty liver and clinical PsA was statistically significant. CONCLUSIONS: Older age, alcohol drinking, elevated hs-CRP, and the presence of fatty liver at less than 45 years old appear to increase the risk of transition from subclinical to clinical PsA. These findings call for a need to manage these risk factors.

5.
Dermatol Ther ; 34(3): e14906, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33611826

RESUMO

There is insufficient evidence concerning the efficacy of wet silver-containing dressings for wound healing in pemphigus vulgaris (PV). In this randomized, controlled clinical trial, 58 patients with PV skin erosions (10%-70% body surface area) were assigned to receive either wet silver-containing dressings (n = 28) or wet to dry povidone-iodine dressings as a control (n = 30). The patients in the treatment group demonstrated a significant improvement in the number of dressing changes, wound healing time, and duration of hospital stay compared with the control group. Patients treated with wet silver dressings had significantly lower NRS pain scores and reported better subjective satisfaction compared with the control group. The only adverse reactions were an occasional abnormal discharge or infection, but there was no difference between the two groups. In our study the wet silver-containing dressings were safe and effective for the treatment of wound healing in PV patients.


Assuntos
Pênfigo , Povidona-Iodo , Bandagens , Humanos , Pênfigo/diagnóstico , Pênfigo/terapia , Povidona-Iodo/efeitos adversos , Prata/efeitos adversos , Cicatrização
6.
Comput Biol Med ; 131: 104242, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33578070

RESUMO

MOTIVATION: Warfarin is a widely used oral anticoagulant, but it is challenging to select the optimal maintenance dose due to its narrow therapeutic window and complex individual factor relationships. In recent years, machine learning techniques have been widely applied for warfarin dose prediction. However, the model performance always meets the upper limit due to the ignoration of exploring the variable interactions sufficiently. More importantly, there is no efficient way to resolve missing values when predicting the optimal warfarin maintenance dose. METHODS: Using an observational cohort from the Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, we propose a novel method for warfarin maintenance dose prediction, which is capable of assessing variable interactions and dealing with missing values naturally. Specifically, we examine single variables by univariate analysis initially, and only statistically significant variables are included. We then propose a novel feature engineering method on them to generate the cross-over variables automatically. Their impacts are evaluated by stepwise regression, and only the significant ones are selected. Lastly, we implement an ensemble learning based approach, LightGBM, to learn from incomplete data directly on the selected single and cross-over variables for dosing prediction. RESULTS: 377 unique patients with eligible and time-independent 1173 warfarin order events are included in this study. Through the comprehensive experimental results in 5-fold cross-validation, our proposed method demonstrates the efficiency of exploring the variable interactions and modeling on incomplete data. The R2 can achieve 75.0% on average. Moreover, the subgroup analysis results reveal that our method performs much better than other baseline methods, especially in the medium-dose and high-dose subgroups. Lastly, the IWPC dosing prediction model is used for further comparison, and our approach outperforms it by a significant margin. CONCLUSION: In summary, our proposed method is capable of exploring the variable interactions and learning from incomplete data directly for warfarin maintenance dose prediction, which has a great premise and is worthy of further research.


Assuntos
Algoritmos , Varfarina , Anticoagulantes , China , Humanos , Aprendizado de Máquina
7.
Environ Pollut ; 268(Pt A): 115822, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33130444

RESUMO

Understanding future climate change requires accurate estimates of the impacts of atmospheric nitrogen (N) deposition, composed of both inorganic and organic compounds, on greenhouse gas (GHG) fluxes in grassland ecosystems. However, previous studies have focused on inorganic compounds and have not considered the potential effects of organic N sources. Here, we conducted a grassland experiment that included organic, inorganic N, and a mix of them at a ratio of 4:6, with two input rates, to study N inputs induced CO2, CH4, and N2O fluxes, as well as the potential abiotic and biotic mechanisms driving the fluxes. We found that N compositions significantly affected fluxes each of the three GHGs. Greater organic N decreased the impacts of N addition on CO2 and N2O emissions, caused primarily by low rates of increase in substrates (soil available N) for production of CO2 and N2O resulting from high ammonia volatilization rather than changes in microbial activity. Also, greater organic N slightly stimulated CH4 uptake. Nitrogen composition effects on CO2 emissions and CH4 uptake were independent of N input rates and measurement dates, but N2O emissions showed stronger responses to inorganic N under high N addition and in June. These results suggest that future studies should consider the source of N to improve our prediction of future climate impact of N deposition, and that management of N fertilization can help mitigate GHG emissions.


Assuntos
Dióxido de Carbono , Nitrogênio , Dióxido de Carbono/análise , Ecossistema , Monitoramento Ambiental , Pradaria , Metano/análise , Óxido Nitroso/análise , Solo
8.
J Opt Soc Am A Opt Image Sci Vis ; 37(6): 1008-1013, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32543603

RESUMO

We propose and theoretically analyze a single-order diffractive optical element, termed binary sinusoidal multilayer grating (BSMG), to effectively suppress high-order diffractions while retaining high diffraction efficiency in the first order. The key idea is to integrate sinusoidal-shaped microstructures with high-reflectivity multilayer coatings. The dependence of the high-order diffraction property on the microstructure shape and multilayer coatings is investigated. Theoretical calculation reveals that the second-, third-, fourth-, and fifth-order diffraction efficiencies are as low as 0.01%. Strikingly, we show that first-order relative diffraction efficiency (the ratio between the intensity of the first diffraction order versus that of the reflected light) as high as 97.7% can be achieved. Thus, the proposed BSMG should be highly advantageous in future development and application of tender x-ray spectroscopy.

9.
Plant Physiol Biochem ; 151: 323-333, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32251957

RESUMO

Soil salinity of fields is often non-uniform. To obtain a better understanding of molecular response to non-uniform salt stress, we conducted transcriptomic analysis on the leaves and roots of alfalfa grown under 0/0, 200/200, and 0/200 mM NaCl treatments. A total of 233,742 unigenes were obtained from the assembled cDNA libraries. There were 98 and 710 unigenes identified as significantly differentially expressed genes (DEGs) in the leaves of non-uniform and uniform salt treatment, respectively. Furthermore, there were 5178 DEGs in the roots under uniform salt stress, 273 DEGs in the non-saline side and 4616 in the high-saline side roots under non-uniform salt stress. Alfalfa treated with non-uniform salinity had greater dry weight and less salt damage compared to treatment with uniform salinity. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEGs in roots revealed that both sides of the non-uniform salinity were enriched in pathways related to "phenylpropanoid biosynthesis" and "linoleic acid metabolism"; and "MAPK signaling pathway-plant" was also indicated as a key pathway in the high-saline roots. We also combined a set of important salt-response genes and found that roots from the non-saline side developed more roots with increased water uptake by altering the expression of aquaporins and genes related to growth regulation. Moreover, the hormone signal transduction and the antioxidant pathway probably play important roles in inducing more salt-related genes and increasing resistance to non-uniform salt stress on both sides of the roots.


Assuntos
Medicago sativa , Tolerância ao Sal , Transcriptoma , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Medicago sativa/genética , Medicago sativa/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Salinidade , Estresse Salino/genética , Tolerância ao Sal/genética
10.
J Biol Chem ; 294(51): 19565-19576, 2019 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-31719145

RESUMO

Endothelial nitric oxide (NO) synthase (eNOS) plays a critical role in the maintenance of blood vessel homeostasis. Recent findings suggest that cytoskeletal dynamics play an essential role in regulating eNOS expression and activation. Here, we sought to test whether modulation of cytoskeletal dynamics through pharmacological regulation of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation affects eNOS expression and endothelial function in vitro and in vivo We found that tubulin acetylation inducer (tubacin), a compound that appears to selectively inhibit HDAC6 activity, dramatically increased eNOS expression in several different endothelial cell lines, as determined by both immunoblotting and NO production assays. Mechanistically, we found that these effects were not mediated by tubacin's inhibitory effect on HDAC6 activity, but rather were due to its ability to stabilize eNOS mRNA transcripts. Consistent with these findings, tubacin also inhibited proinflammatory cytokine-induced degradation of eNOS transcripts and impairment of endothelium-dependent relaxation in the mouse aorta. Furthermore, we found that tubacin-induced up-regulation in eNOS expression in vivo is associated with improved endothelial function in diabetic db/db mice and with a marked attenuation of ischemic brain injury in a murine stroke model. Our findings indicate that tubacin exhibits potent eNOS-inducing effects and suggest that this compound might be useful for the prevention or management of endothelial dysfunction-associated cardiovascular diseases.


Assuntos
Anilidas/farmacologia , Endotélio Vascular/patologia , Desacetilase 6 de Histona/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Óxido Nítrico Sintase Tipo III/metabolismo , Óxido Nítrico/química , Acetilação , Animais , Aorta/metabolismo , Encéfalo/patologia , Isquemia Encefálica/patologia , Modelos Animais de Doenças , Feminino , Regulação Enzimológica da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Acidente Vascular Cerebral/fisiopatologia , Tubulina (Proteína)/química , Regulação para Cima
12.
Front Pharmacol ; 9: 176, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29593530

RESUMO

Hypertension-induced cardiac apoptosis is a major contributor to early-stage heart-failure. Our previous studies have found that p53-mediated mitochondrial fission is involved in aldosterone-induced podocyte apoptosis. However, it is not clear that whether p53-induced mitochondrial fission is critical for hypertensive Angiotensin II (AngII)-induced cardiomyocyte apoptosis. In this study, we found that inhibition of the mitochondrial fission protein Drp1 (dynamin-related protein 1) by Mdivi-1 prevented cardiomyocyte apoptosis and cardiac remodeling in SHRs. In vitro we found that treatment of cultured neonatal rat cardiomyocytes with AngII induced Drp1 expression, mitochondrial fission, and apoptosis. Knockdown of Drp1 inhibited AngII-induced mitochondrial fission and cardiomyocyte apoptosis. Furthermore, AngII induced p53 acetylation. Knockdown of p53 inhibited AngII-induced Drp1 expression, mitochondrial fission, and cardiomyocyte apoptosis. Besides, we found that Sirt1 was able to reverse AngII-induced p53 acetylation and its binding to the Drp1 promoter, which subsequently inhibited mitochondrial fission and eventually attenuated cardiomyocyte apoptosis. Collectively, these results suggest that AngII degrades Sirt1 to increase p53 acetylation, which induces Drp1 expression and eventually results in cardiomyocyte apoptosis. Sirt1/p53/Drp1dependent mitochondrial fission may be a valuable therapeutic target for hypertension induced heart failure.

13.
Int J Nanomedicine ; 13: 1327-1339, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29563790

RESUMO

Purpose: Breast cancer is the most common cancer among women. Pemetrexed, a new generation antifolate drug, is one of the primary treatments for breast cancer. However, multidrug resistance (MDR) in breast cancer greatly hampers the therapeutic efficacy of chemotherapies such as pemetrexed. Nanomedicine is emerging as a promising alternative technique to overcome cancer MDR. Thus, pemetrexed-loaded d-alpha tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) liposomes (liposomal pemetrexed) were developed as a strategy to overcome MDR to pemetrexed in breast cancer. Materials and methods: Liposomal pemetrexed was developed using the calcium acetate gradient method. The cytotoxic effects, apoptosis-inducing activity, in vivo distribution, and antitumor activity of liposomal pemetrexed were investigated. Results: Liposomal pemetrexed was small in size (160.77 nm), with a small polydispersity of <0.1. The encapsulation efficacy of liposomal pemetrexed was 63.5%, which is rather high for water-soluble drugs in liposomes. The IC50 of liposomal pemetrexed following treatment with MDR breast cancer cells (MCF-7 cells overexpressing ABCC5) was 2.6-fold more effective than pemetrexed. The in vivo biodistribution study showed that the liposomes significantly accumulated in tumors 24 h after injection. The antitumor assay in mice bearing MDR breast cancer xenograft tumors confirmed the superior antitumor activity of liposomal pemetrexed over pemetrexed. It was also found that the improved therapeutic effect of liposomal pemetrexed may be attributed to apoptosis through both extrinsic and intrinsic pathways. Conclusion: Liposomal pemetrexed represents a potential therapeutic approach for overcoming breast cancer MDR.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Pemetrexede/uso terapêutico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Feminino , Humanos , Concentração Inibidora 50 , Lipossomos , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Nus , Pemetrexede/farmacologia , Distribuição Tecidual , Transfecção
14.
J Agric Food Chem ; 66(8): 1743-1750, 2018 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-29401393

RESUMO

Magnesium (Mg) is important for both plant photosynthesis and protein synthesis. Nevertheless, latent Mg deficiencies are common, and Mg addition has shown an improved yield. Might such an increasing yield cause "hidden" hunger for microelements and protein, and if so, what is the mechanism? We conducted two greenhouse experiments using low-Mg soil to investigate (i) effects of five levels of Mg fertilizer (20-400 mg kg-1) on eight elements and crude protein concentrations in annual ryegrass and white clover and (ii) if any protein effects of the Mg fertilizer depend upon soil nitrogen (N). Mg addition significantly increased the yield in both species, simultaneously decreasing concentrations of crude protein, calcium (Ca), sodium, manganese, and potassium/Mg and Ca/Mg ratios caused by increased biomass dilution effects and increased [Mg]. Other mineral dilution effects of the Mg fertilizer depended upon species: the concentration of phosphorus decreased only in ryegrass, and the concentration of zinc decreased only in white clover. Mg addition in soil rich with available N (from N fertilizer in ryegrass or biological fixation in white clover) showed an increased crude protein content as well as increased yield in the forage of both species. These results suggest that the Mg fertilizer can affect the protein content positively or negatively depending upon available N in soil and that sufficiently available N must be ensured along with Mg addition in low Mg soils.


Assuntos
Fertilizantes/análise , Lolium/química , Magnésio/análise , Medicago/química , Nitrogênio/análise , Proteínas de Plantas/análise , Lolium/metabolismo , Magnésio/metabolismo , Medicago/metabolismo , Nitrogênio/metabolismo , Proteínas de Plantas/metabolismo , Potássio/análise , Potássio/metabolismo , Solo/química
15.
Biochim Biophys Acta Mol Basis Dis ; 1863(11): 2954-2963, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28847511

RESUMO

We previously demonstrated that histamine H4 receptor (HRH4) played important roles to suppress epithelial-to-mesenchymal transition (EMT) progress in non-small cell lung cancer (NSCLC). Furthermore, recent investigations suggested that genetic variations in HRH4 gene affected HRH4 function and eventually contributed to certain HRH4-related diseases. However, the relations between polymorphisms in HRH4 gene and NSCLC as well as their underlying mechanisms remain largely uninvestigated. This study aims to investigate the genetic effect of a nonsynonymous HRH4 polymorphism (rs11662595) on HRH4 function and its association with NSCLC both basically and clinically. For basic experiments, A549 cells were transfected with either wild type or rs11662595 mutated HRH4 clone and subjected to both in vitro and in vivo experiments. We showed that rs11662595 significantly decreased the ability of HRH4 to activate Gi protein, which resulted in facilitation of EMT progress, cell proliferation, and invasion behavior in vitro. Moreover, in vivo experiments also showed that rs11662595 attenuated the anti-EMT effects of HRH4 agonist in inoculated nu/nu mice. For clinical experiments, we performed a prospective cohort study among 624 NSCLC patients and further proved that rs11662595 was responsible for the prognosis, degree of malignancy and metastasis of NSCLC. In conclusion, these findings reveal that rs11662595 is a loss-of-function polymorphism that results in dysfunction of HRH4 and attenuates the anti-EMT function of HRH4 in NSCLC, which provides a promising biomarker for prognosis and therapy of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Transição Epitelial-Mesenquimal , Neoplasias Pulmonares/metabolismo , Mutação , Proteínas de Neoplasias/metabolismo , Receptores Histamínicos H4/metabolismo , Células A549 , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Nus , Proteínas de Neoplasias/genética , Polimorfismo Genético , Estudos Prospectivos , Receptores Histamínicos H4/genética
16.
J Agric Food Chem ; 65(16): 3253-3258, 2017 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-28375633

RESUMO

Magnesium (Mg) plays important roles in photosynthesis and protein synthesis; however, latent Mg deficiencies are common phenomena that can influence food quality. Nevertheless, the effects of Mg fertilizer additions on plant carbon (C):nitrogen (N):phosphorus (P) stoichiometry, an important index of food quality, are unclear and the underlying mechanisms unexplored. We conducted a greenhouse experiment using low-Mg in situ soil without and with a gradient of Mg additions to investigate the effect of Mg fertilizer on growth and stoichiometry of maize and soybean and also measure these plants' main symbiotic microorganisms: arbuscular mycorrhizal fungi (AMF) and rhizobium, respectively. Our results showed that Mg addition significantly improved both plant species' growth and also increased N and P concentrations in soybean and maize, respectively, resulting in low C:N ratio and high N:P ratio in soybean and low C:P and N:P ratios in maize. These results presumably stemmed from the increase of nutrients supplied by activation-enhanced plant symbiotic microorganisms, an explanation supported by statistically significant positive correlations between plant stoichiometry and plants' symbiotic microorganisms' increased growth with Mg addition. We conclude that Mg supply can improve plant growth and alter plant stoichiometry via enhanced activity of plant symbiotic microorganisms. Possible mechanisms underlying this positive plant-soil feedback include an enhanced photosynthetic product flow to roots caused by adequate Mg supply.


Assuntos
Fertilizantes/análise , Magnésio/metabolismo , Micorrizas/metabolismo , Rhizobium/metabolismo , Soja/crescimento & desenvolvimento , Soja/microbiologia , Simbiose , Zea mays/crescimento & desenvolvimento , Magnésio/análise , Micorrizas/crescimento & desenvolvimento , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Raízes de Plantas/microbiologia , Rhizobium/crescimento & desenvolvimento , Microbiologia do Solo , Soja/química , Soja/fisiologia , Zea mays/química , Zea mays/microbiologia , Zea mays/fisiologia
17.
Gene Expr Patterns ; 22(2): 37-45, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27826126

RESUMO

Tetratricopeptide repeat domain 36 (Ttc36), whose coding protein belongs to tetratricopeptide repeat (TPR) motif family, has not been studied extensively. We for the first time showed that Ttc36 is evolutionarily conserved across mammals by bioinformatics. Rabbit anti-mouse Ttc36 polyclonal antibody was generated by injecting synthetic full-length peptides through "antigen intersection" strategy. Subsequently, we characterized Ttc36 expression profile in mouse, showing its expression in liver and kidney both from embryonic day 15.5 (E15.5) until adult, as well as in testis. Immunofluorescence staining showed that Ttc36 is diffusely expressed in liver, however, specifically in kidney cortex. Thus, we further compare Ttc36 with proximal tubules (PT) marker Lotus Tetragonolobus Lectin (LTL) and distal tubules (DT) marker Calbindin-D28k respectively by double immunofluorescence staining. Results showed the co-localization of Ttc36 with LTL rather than Calbindin-D28k. Collectively, on the basis of the expression pattern, Ttc36 is specifically expressed in proximal distal tubules.


Assuntos
Proteínas de Transporte/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Proteínas de Membrana/genética , Proteínas Mitocondriais/genética , Domínios Proteicos/genética , Motivos de Aminoácidos/genética , Animais , Calbindina 1/biossíntese , Calbindina 1/genética , Proteínas de Transporte/biossíntese , Túbulos Renais Proximais/metabolismo , Lectinas/biossíntese , Lectinas/genética , Camundongos , Coelhos , Sequências Repetitivas de Aminoácidos/genética
18.
Am J Transl Res ; 7(9): 1553-63, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26550455

RESUMO

Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes and may lead to end-stage renal disease (ESRD) and chronic renal failure. The aim of this study was to determine whether low-molecular-weight fucoidan (LMWF) can reduce harmful transforming growth factor-ß (TGF-ß)-mediated renal fibrosis in DN using in vitro and in vivo experimental models. The experimental results showed that LMWF significantly reversed TGF-ß1-induced epithelial-mesenchymal transition and dose-dependently inhibited accumulation of extracellular matrix proteins, including connective tissue growth factor and fibronectin. It was found that LMWF significantly reduced blood urea nitrogen and blood creatinine in both type 1 and type 2 diabetic rat models. H&E, PAS and Masson's trichrome staining of kidney tissue showed LMWF significantly reduced renal interstitial fibrosis. Treatment with LMWF significantly increased E-cadherin expression and reduced α-SMA, CTGF and fibronectin expression in both type 1 and type 2 diabetic models. LMWF also decreased the phosphorylation of Akt, ERK1/2, p38 and Smad3 in vitro and in vivo. These data suggest that LMWF may protect kidney from dysfunction and fibrogenesis by inhibiting TGF-ß pathway and have the potential benefit to slow down the progression of DN.

19.
Pharmacology ; 95(5-6): 279-84, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25997622

RESUMO

This study explored nephrotoxicity in elderly Chinese patients after exposure to vancomycin and other nephrotoxic risk factors. This was a single-center retrospective study. The patient population included those who were ≥60 years of age, had normal baseline serum creatinine values, and received vancomycin for ≥48 h between January 1, 2013 and August 30, 2014. Nephrotoxicity occurred in 29% of 124 patients. A baseline creatinine clearance ≥63.5 ml/min was more common in the nephrotoxic group. Patients with high (≥15 mg/l) rather than low (<15 mg/l) average vancomycin troughs had elevated nephrotoxicity (47.2 vs. 27.3%, p = 0.0001). Of the comorbid conditions evaluated, there were more patients with shock (p = 0.001), hypertension (p = 0.020) and congestive heart failure (p = 0.04) in the nephrotoxic group. Drugs frequently given at the same time with vancomycin, such as angiotensin receptor blockers and furosemide, were also associated with increased nephrotoxic risk. In conclusion, nephrotoxicity was frequently observed in patients with concurrent vancomycin trough concentrations ≥15 µg/ml and hypertension, shock, congestive heart failure. In addition, drugs concurrently used with vancomycin may also increase its nephrotoxicity. Therefore, renal function and vancomycin serum troughs should be closely monitored, especially in patients with other renal injury risk factors.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Antibacterianos/efeitos adversos , Vancomicina/efeitos adversos , Injúria Renal Aguda/epidemiologia , Idoso , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
Am J Transl Res ; 7(12): 2706-15, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26885268

RESUMO

AIM: Subcortical ischemic vascular dementia (SIVD) induced by chronic hypoperfusion is a common cause of vascular dementia. The aim of this study was to determine whether the protective effect of carnosine on white matter lesion after chronic cerebral hypoperfusion through suppressing astrocyte activation. METHODS: Adult male mice (C57BL/6 strain) were subjected to permanent occlusion of the right unilateral common carotid arteries (rUCCAO) and treated with carnosine or histidine. Open field test, freezing test, Klüver-Barrera staining, immunohistochemical analyses and western blot were performed after rUCCAO. RESULTS: We found that carnosine ameliorated white matter lesion and cognitive impairment after rUCCAO. Carnosine suppressed the activation of astrocyte in both wide type mice and histidine decarboxylase knockout mice. However, administration of histidine did not show the same effect. We found that there were no differences between rUCCAO group and sham group for the expression of glutamate transporter-1 (GLT-1) and glutamate/aspartate transporter (GLAST). Furthermore, carnosine significantly attenuated the increase of inflammatory cytokine interferon gama. CONCLUSION: These data suggest carnosine induced neuroprotection during SIVD in mice is not dependent on the histaminergic pathway or the regulation of the expression of GLT-1 and GLAST, but may be due to a suppression of astrocyte activation and inflammatory cytokine release.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...