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1.
J Orthop Surg Res ; 15(1): 42, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32041613

RESUMO

OBJECTIVE: This study aims to investigate the efficiency of fascia iliaca compartment block (FICB) combined with dexmedetomidine (DEX) in postoperative and inflammation management for elder patients after total hip arthroplasty. METHODS: The present randomized controlled study included a total of 119 elder patients who received total hip arthroplasty in our hospital from March 2016 to December 2018. These patients were divided into three groups: control group, patients received routine general anesthesia; FICB group, patients received additional FICB after surgery; and combined group, patients received both pre-treatment of DEX and post-treatment of fascia iliaca compartment block. The serum levels of interleukin (IL)-1ß, IL-6, and C-reactive protein (CRP) were measured by ELISA. The visual analog scale (VAS) score was measured at 12, 24, 48, and 72 h after surgery, and the patient-controlled intravenous analgesia (PCIA) pressing time within 48 h after surgery was also recorded. The Pittsburgh sleep quality index (PSQI) was used to measure the sleep quality before and at 1 month after surgery. RESULTS: The VAS scores were significantly lower in patients in the combined group, when compared with the other two groups, at 12, 24, 48, and 72 h after surgery. In addition, the VAS scores at all time points were significantly lower in the FICB group than the control group. The PCIA pressing times were also remarkably lower in the combined group. At 4, 24, 48, and 72 h after surgery, the serum levels of these inflammatory factors were the lowest in the combined group, and the PSQI scores were significantly lower in the combined group, when compared with the other two groups, while the control group had the highest PSQI scores among the three groups. There was no severe side effects and significant difference observed. CONCLUSION: FICB combined with DEX reduced the postoperative pain, improved the sleep condition, and decreased the serum levels of inflammatory factors after total hip arthroplasty.

2.
J Exp Bot ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32072171

RESUMO

Flesh lignification is a specific chilling response which causes quality deterioration of stored red-fleshed loquat fruit (Eribotrya japonica) and is one aspect of wider chilling injury. APETALA2/ETHLENE RESPONSIVE FACTOR (AP2/ERF) transcription factors are important regulators of plant low temperature responses and lignin biosynthesis. In this study, expression and action of twenty-seven AP2/ERF genes from loquat fruit (red-fleshed 'Luoyangqing') were investigated in order to identify TFs regulating low temperature-induced lignification. EjERF27, EjERF30, EjERF36, and EjERF39 were significantly induced by 0 oC storage but inhibited by low temperature conditioning treatment (LTC, pre-storage at 5 oC for 6 days before storage at 0 oC, which reduces low temperature-induced lignification), and their transcript levels were positively correlated with flesh lignification. Dual luciferase assay indicated that EjERF39 could trans-activate the promoter of the lignin biosynthetic gene Ej4CL1 and electrophoretic mobility shift assay (EMSA) confirmed that EjERF39 recognizes the DRE element in the promoter region of Ej4CL1. Furthermore, the combination of EjERF39 with a previously characterized EjMYB8 synergistically trans-activated the Ej4CL1 promoter and both TFs showed expression patterns correlated with lignification in postharvest treatments and red-fleshed 'Luoyangqing' and white-fleshed 'Ninhaibai' cultivars with different lignification responses. Bimolecular fluorescence complementation (BiFC) and luciferase complementation imaging (LCI) assays confirmed direct protein-protein interaction between EjERF39 and EjMYB8. These data indicate that EjERF39 is a novel cold-responsive transcriptional activator of Ej4CL1 which forms a synergistic activator complex with EjMYB8 and contributes to loquat fruit lignification at low temperatures.

3.
J Exp Bot ; 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31926021

RESUMO

Most persimmon (Diospyros kaki) cultivars are astringent and require postharvest de-astringency treatments such as 95% CO2 (high CO2 treatment) to make them acceptable to consumers. High CO2 treatment can, however, also induce excessive softening, which can be reduced by adding 1-methylcyclopropene (1-MCP). Previous studies revealed that genes encoding ETHYLENE RESPONSE FACTORS (ERFs) DkERF8/16/19 could trans-activate cell wall degrading enzyme xyloglucan endotransglycosylase/hydrolase gene (DkXTH9) associated with persimmon fruit softening. In this study, the RNA-seq data between three treatments (high CO2, CO2+1-MCP and control) were compared. 227 differentially expressed genes (DEGs), with 17 transcription factors (TFs), were predicted to be related to persimmon post-deastringency softening. Dual-luciferase assays indicated that DkNAC9 activated the DkEGase1 promoter 2.64-fold. Synergistic effects on transcription from the DkEGase1 involving DkNAC9 and previously reported DkERF8/16 were identified. Electrophoretic mobility shift assay (EMSA) indicated that DkNAC9 could physically bind to the DkEGase1 promoter. Bimolecular fluorescence complementation (BiFC) and firefly luciferase complementation imaging assays (LCI) indicated protein-protein interactions between DkNAC9 and DkERF8/16. Based on these findings, DkNAC9 is a direct transcriptional activator of DkEGase1, which can cooperate with DkERF8/16 to enhance post-deastringency softening.

5.
Bioengineered ; 11(1): 103-115, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-31903833

RESUMO

Abscisic acid (ABA) signaling regulates plant growth and development and participates in response to abiotic stressors. However, details about the PYL-PP2C-SnRK2 gene family, which is the core component of ABA signaling in Camellia sinensis, are unknown. In this work, we identified 14 pyrabactin resistance-likes (PYLs), 84 type 2C protein phosphatase (PP2Cs), and 8 SNF1-related protein kinase 2s (SnRK2s) from C. sinensis. The transcriptomic analysis indicated that PYL-PP2C-SnRK2s were associated with changes of leaf color and the response of C. sinensis to drought and salt stressors. Changes of the expression of Snrk2s were not significant in the process of leaf color change or drought and salt stress response, suggesting that PYLs and PP2Cs may not interact with SnRK2s in C. sinensis during these processes. Finally, Gene Regulatory Network (GRN) construction and interaction networks analysis demonstrated that PYLs and PP2Cs were associated with multiple metabolic pathways during the changes of leaf color.

6.
Int J Mol Sci ; 20(22)2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31717553

RESUMO

Hypoxic environments are generally undesirable for most plants, but for astringent persimmon, high CO2 treatment (CO2 > 90%), also termed artificial high-CO2 atmosphere (AHCA), causes acetaldehyde accumulation and precipitation of soluble tannins and could remove astringency. The multiple transcriptional regulatory linkages involved in persimmon fruit deastringency have been advanced significantly by characterizing the ethylene response factors (ERFs), WRKY and MYB; however, the involvement of zinc finger proteins for deastringency has not been investigated. In this study, five genes encoding C2H2-type zinc finger proteins were isolated and designed as DkZF1-5. Phylogenetic and sequence analyses suggested the five DkZFs could be clustered into two different subgroups. qPCR analysis indicated that transcript abundances of DkZF1/4 were significantly upregulated during AHCA treatment (1% O2 and 95% CO2) at day 1, DkZF2/5 at both day 1 and 2, while DkZF3 at day 2. Dual-luciferase assay indicated DkZF1 and DkZF2 as the activators of deastringency-related structural genes (DkPDC2 and DkADH1) and transcription factors (DkERF9/10). Moreover, combinative effects between various transcription factors were investigated, indicating that DkZF1 and DkZF2 synergistically showed significantly stronger activations on the DkPDC2 promoter. Further, both bimolecular fluorescence complementation (BiFC) and yeast two hybrid (Y2H) assays confirmed that DkZF2 had protein-protein interactions with DkZF1. Thus, these findings illustrate the regulatory mechanisms of zinc finger proteins for persimmon fruit deastringency under AHCA.

7.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 44(8): 850-856, 2019 Aug 28.
Artigo em Chinês | MEDLINE | ID: mdl-31570670

RESUMO

OBJECTIVE: To investigate the effects of genistein (Gen) on nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in myocardial tissues of diabetic rats.
 Methods: Thirty-two male SD rats were randomly divided into 4 groups: a normal control (NC) group, a diabetic control (DM) group, a low-dose Gen treatment (L-Gen) group, and a high-dose Gen treatment (H-Gen) group (n=8). Intraperitoneal injection of streptozotocin was utilized to induce diabetic rat model. After the establishment of diabetic model, the rats in L-Gen and H-Gen groups were intragastric administration with 10 and 50 mg/kg Gen solution. Following 8 weeks, the left ventricular hemodynamic parameters and fasting blood glucose (FBG) levels were measured. The levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) in myocardial tissue were determined. The ultrastructure of myocardium was observed under transmission electron microscopy. The expression of HO-1 at mRNA level in myocardial tissue was detected by RT-PCR. The protein levels of Nrf2 and HO-1 in myocardial tissue were detected by Western blotting. 
 Results: Compared with the NC group, left ventricular systolic pressure (LVSP), maximal rise/fall rate of left ventricular pressure (±dp/dtmax), and the levels of GSH-Px, SOD and CAT were decreased (all P<0.01), while the left ventricular end-diastolic pressure (LVEDP), FBG and MDA were increased (all P<0.01) in the DM group. The myocardial ultrastructure was obviously damaged, and the expressions of myocardial Nrf2 and HO-1 were significantly decreased (both P<0.01) in the DM group. Compared with the DM group, there was no difference in FBG in the L-Gen group, while ±dp/dtmax and LVSP were significantly increased (all P<0.05), and LVEDP and MDA were decreased (P<0.05 or P<0.01), and the levels of GSH-Px, SOD and CAT were increased (P<0.05 or P<0.01) in the L-Gen group. The myocardial ultrastructure damage was alleviated and the expressions of Nrf2 and HO-1 were increased (both P<0.01) in the L-Gen group. Compared with L-Gen group, the aforementioned indexes were improved in the H-Gen group (P<0.05 or P<0.01).
 Conclusion: Genistein exerted antioxidant effects on myocardial injury in diabetic rats, and the mechanisms might be related to regulating the Nrf2/HO-1 pathway and enhancing the activities of antioxidant enzymes in myocardial tissues.


Assuntos
Diabetes Mellitus Experimental , Animais , Genisteína , Heme Oxigenase (Desciclizante) , Masculino , Miocárdio , Fator 2 Relacionado a NF-E2 , Ratos , Ratos Sprague-Dawley
8.
Front Pharmacol ; 10: 754, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31333468

RESUMO

Background: Polymyxins are a last-line class of antibiotics against multidrug-resistant Acinetobacter baumannii. However, polymyxin resistance can emerge with monotherapy, highlighting the need for synergistic combination therapies. Polymyxins in combination with ß-lactams have shown remarkable synergy against multidrug-resistant A. baumannii. Methods: Liquid chromatography-mass spectrometry-based metabolomics was conducted to investigate the metabolic perturbations in an A. baumannii clinical isolate, AB090342, in response to colistin (1 mg/L), sulbactam (128 mg/L), and their combination at 1, 4, and 24 h. Metabolomics data were analyzed using univariate and multivariate statistics, and metabolites showing ≥2-fold changes were subjected to pathway analysis. Results: The synergistic activity of colistin-sulbactam combination was initially driven by colistin through perturbation of fatty acid and phospholipid levels at 1 h. Cell wall biosynthesis was perturbed by sulbactam alone and the combination over 24 h; this was demonstrated by the decreased levels of two important precursors, uridine diphosphate-N-acetylglucosamine and uridine diphosphate-N-acetylmuramate, together with perturbed lysine and amino sugar metabolism. Moreover, sulbactam alone and the combination significantly depleted nucleotide metabolism and the associated arginine biosynthesis, glutamate metabolism, and pentose phosphate pathway. Notably, the colistin-sulbactam combination decreased amino acid and nucleotide levels more dramatically at 4 h compared with both monotherapies. Conclusions: This is the first metabolomics study revealing the time-dependent synergistic activity of colistin and sulbactam against A. baumannii, which was largely driven by sulbactam through the inhibition of cell wall biosynthesis. Our mechanistic findings may help optimizing synergistic colistin combinations in patients.

9.
Bioanalysis ; 11(10): 941-955, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31218900

RESUMO

Aim: This study aimed to develop and validate a method for better therapeutic monitoring of vancomycin serum concentration. Methods & results: An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to minimize the interference of crystalline degradation product and matrix. It was compared with chemiluminescence microparticle immunoassay (CMIA) and ultra-performance liquid chromatography with ultraviolet detection (UPLC-UV) in the performance of testing normal, on-dialysis and hemolytic serum samples. For on-dialysis samples, a moderate correlation (r = 0.534) was observed between UPLC-UV and UPLC-MS/MS. In testing hemolytic samples, ten (10/85, 11.8%) samples were overestimated by CMIA method. Conclusion: Vancomycin concentration determined by CMIA, UPLC-UV was more affected by various panels of serum samples than UPLC-MS/MS assay, suggesting that UPLC-MS/MS is a more reliable and promising tool for clinical vancomycin therapeutic drug monitoring.


Assuntos
Artefatos , Análise Química do Sangue/métodos , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Vancomicina/sangue , Métodos Analíticos de Preparação de Amostras , Hemólise , Humanos , Hiperlipidemias/sangue , Espectrofotometria Ultravioleta
10.
Plant Physiol Biochem ; 139: 731-737, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059995

RESUMO

Many transcription factors (TFs), including NACs and MYBs, are involved in regulation of lignin biosynthesis during plant development and in responses to biotic and abiotic stresses. The lignin biosynthesis gene Ej4CL1 has been identified as a target for cold-induced TFs. We isolated a bHLH gene from loquat, EjbHLH1, the expression of which was negatively correlated with cold-induced fruit lignification. During low temperature storage (0 °C), EjbHLH1 transcripts were stable but accumulated during low-temperature conditioning (LTC) treatment, an acclimation process that reduces lignification during subsequent storage at 0 °C. Dual luciferase assays showed EjbHLH1 could repress Ej4CL1 promoter, but yeast one hybrid assay indicated EjbHLH1 is not able to bind to the Ej4CL1 promoter. Bimolecular fluorescence complementation (BIFC) indicated that EjbHLH1 could interact with EjAP2-1 and EjMYB2, two previously characterized fruit lignification related transcription factors and firefly luciferase complementation imaging assay indicated EjbHLH1, EjMYB2 and EjAP2-1 could form a ternary complex which enhanced repression of transcription from the Ej4CL1 promoter, reducing lignification at 0 °C.


Assuntos
Eriobotrya/metabolismo , Frutas/metabolismo , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Eriobotrya/genética , Frutas/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Temperatura Ambiente , Fatores de Transcrição/genética
11.
J Exp Bot ; 70(12): 3111-3123, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-30994176

RESUMO

'Jimba', a well-known white flowered chrysanthemum cultivar, occasionally and spontaneously produces red colored petals under natural cultivation, but there is little information about the molecular regulatory mechanism underlying this process. We analysed the expression patterns of 91 MYB transcription factors in 'Jimba' and 'Turning red Jimba' and identified an R3 MYB, CmMYB#7, whose expression was significantly decreased in 'Turning red Jimba' compared with 'Jimba', and confirmed it is a passive repressor of anthocyanin biosynthesis. CmMYB#7 competed with CmMYB6, which together with CmbHLH2 is an essential component of the anthocyanin activation complex, for interaction with CmbHLH2 through the bHLH binding site in the R3 MYB domain. This reduced binding of the CmMYB6-CmbHLH2 complex and inhibited its ability to activate CmDFR and CmUFGT promoters. Moreover, using transient expression assays we demonstrated that changes in the expression of CmMYB#7 accounted for alterations in anthocyanin content. Taken together, our findings illustrate that CmMYB#7 is a negative regulator of anthocyanin biosynthesis in chrysanthemum.

12.
PLoS Biol ; 17(4): e3000096, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31009446

RESUMO

The Orai channel is characterized by voltage independence, low conductance, and high Ca2+ selectivity and plays an important role in Ca2+ influx through the plasma membrane (PM). How the channel is activated and promotes Ca2+ permeation is not well understood. Here, we report the crystal structure and cryo-electron microscopy (cryo-EM) reconstruction of a Drosophila melanogaster Orai (dOrai) mutant (P288L) channel that is constitutively active according to electrophysiology. The open state of the Orai channel showed a hexameric assembly in which 6 transmembrane 1 (TM1) helices in the center form the ion-conducting pore, and 6 TM4 helices in the periphery form extended long helices. Orai channel activation requires conformational transduction from TM4 to TM1 and eventually causes the basic section of TM1 to twist outward. The wider pore on the cytosolic side aggregates anions to increase the potential gradient across the membrane and thus facilitate Ca2+ permeation. The open-state structure of the Orai channel offers insights into channel assembly, channel activation, and Ca2+ permeation.


Assuntos
Canais de Cálcio/metabolismo , Cálcio/metabolismo , Proteínas de Drosophila/metabolismo , Proteína ORAI1/metabolismo , Animais , Cálcio/fisiologia , Membrana Celular/metabolismo , Microscopia Crioeletrônica , Proteínas de Drosophila/genética , Drosophila melanogaster/metabolismo , Ativação do Canal Iônico/fisiologia , Proteínas de Membrana/metabolismo , Proteína ORAI1/genética , Estrutura Secundária de Proteína
13.
J Agric Food Chem ; 67(18): 5204-5211, 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-30998337

RESUMO

Texture attributes such as firmness and lignification are important for fruit quality. Lignification has been widely studied in model plants and energy crops, but fruit lignification has rarely been investigated, despite having an adverse effect on fruit quality and consumer preference. Chilling-induced loquat fruit lignification that occurs after harvest can be alleviated by heat treatment (HT) applied prior to low temperature storage. Enzyme activity assay showed that HT treatment could retard the low temperature-induced increase in cinnamyl alcohol dehydrogenase (CAD) activity. Transcript analysis and substrate activity assays of recombinant CAD proteins highlighted the key role of EjCAD5 in chilling-induced lignin biosynthesis. A novel homeobox-leucine zipper protein ( EjHAT1) was identified as a negative regulator of EjCAD5. Therefore, the effect of HT treatment on lignification may be partially due to the suppression of the EjCAD5 promoter activity by EjHAT1.


Assuntos
Oxirredutases do Álcool/metabolismo , Eriobotrya/enzimologia , Histona Acetiltransferases/metabolismo , Lignina/biossíntese , Proteínas de Plantas/metabolismo , Oxirredutases do Álcool/genética , Temperatura Baixa , Eriobotrya/genética , Eriobotrya/metabolismo , Frutas/enzimologia , Frutas/genética , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas , Histona Acetiltransferases/genética , Temperatura Alta , Proteínas de Plantas/genética , Regiões Promotoras Genéticas
14.
Zhongguo Zhong Yao Za Zhi ; 44(5): 920-926, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-30989850

RESUMO

Anthraquinones,dianthrones and tannins are the main active ingredients of Rheum tanguticum. In this study the three components were determined by HPLC,and the results were analyzed by multiple comparisons,principal components analysis(PCA)and correspondence analysis(CA). The results showed that the contents of components in different growing areas and types(wild and cultivated) reached a significant level(P<0. 05). Baiyu county,Xiaojin county and Ruoergai county had obvious advantages in the accumulation of catechin hydrate,rhien and sensenoside A respectively. The principal component was different in two growing type and the wild environment was conducive to combined anthraquinones accumulation. For active components,normalized planting was better than retail cultivating. Therefore,the effect on the accumulation of chemical components in Rh. tangusticum,should be taken into full account in the selection of the cultural base of Rh. tanguticum. The standardized cultivating is superior to retail cultivating in terms of the accumulation of active ingredients,and standardized planting is inferior to the wild.


Assuntos
Antraquinonas/análise , Rheum/química , Taninos/análise , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/análise , Compostos Fitoquímicos/análise , Plantas Medicinais/química
15.
Oncol Lett ; 17(4): 3899-3909, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30930990

RESUMO

Malignant gastrointestinal neuroectodermal tumors (GNETs) are rare aggressive malignant neoplasms that exclusively occur within the wall of the gastrointestinal tract. The GNET was first described as an 'osteoclast-rich tumor of the gastrointestinal tract with features resembling clear cell sarcoma (CCS) of soft parts' in 2003. Although the GNET shares certain histological features with CCS, it is characterized by a lack of melanocytic differentiation and the presence of non-tumoral osteoclast-like giant cells (OLGCs). The present study reports a case of a GNET of the ileum with intra-abdominal granulomatous nodules, an uncommon accompanying finding, and summarizes the current literature. A 30-year-old woman presented with the symptoms of intestinal obstruction, and a mass was found within the ileum wall. Multiple grey-white nodules were found adhering to the omentum and serosa of the ileum. Histologically, the tumor was located in the muscularis propria and infiltrated the mucosa and the serosa. Tumor cells presented with oval or polygonal nuclei and prominent nucleoli, and were predominantly arranged in nested and pseudopapillary patterns, with the presence of cluster of differentiation (CD)68-positive, scattered OLGC. Immunohistochemically, it was determined that the tumor cells expressed Vimentin, CD56, S-100 and transcription factor SOX-10, while being negative for pan-cytokeratin, cytokeratin (CK)7, CK20, synaptophysin, chromogranin-A, CD117, anoctamin-1, CD34, human melanoma black-45, Melan-A, smooth muscle actin, CD3 and CD20 expression. Ewing sarcoma breakpoint region 1 gene rearrangement was identified by fluorescence in situ hybridization analysis. Ultrastructurally, no typical melanosomes were identified. In addition, the intra-abdominal grey-white nodules were microscopically identified as chronic granulomatous inflammation. The patient received four cycles of adjuvant chemotherapy following routine tumor resection. Due to its rarity and histological similarity with other neoplasms, unfamiliarity with the features of GNETs by surgical pathologists can easily lead to a misdiagnosis. Therefore, comprehensive assessments, including morphology and ancillary studies, are required for an accurate diagnosis of GNET.

16.
Artigo em Inglês | MEDLINE | ID: mdl-30745385

RESUMO

Colistin-based combination therapy has become an important strategy to combat the carbapenem-resistant Acinetobacter baumannii (CRAB). However, the optimal dosage regimen selection for the combination with maximum efficacy is challenging. Checkerboard assay was employed to evaluate the synergy of colistin in combination with meropenem, rifampin, fosfomycin, and minocycline against nine carbapenem-resistant A. baumannii isolates (MIC of meropenem [MICMEM], ≥32 mg/liter) isolated from Chinese hospital-acquired pneumonia (HAP) patients. A static time-kill assay, in vitro dynamic pharmacokinetic/pharmacodynamic (PK/PD) model, and semimechanistic PK/PD modeling were conducted to predict and validate the synergistic effect of the most efficacious combination. Both checkerboard and static time-kill assays demonstrated the superior synergistic effect of the colistin-meropenem combination against all CRAB isolates. In the in vitro PK/PD model, the dosage regimen of 2 g meropenem daily via 3-h infusion combined with steady-state 1 mg/liter colistin effectively suppressed the bacterial growth at 24 h with a 2-log10 decrease, compared with the initial inocula against two CRAB isolates. The semimechanistic PK/PD model predicted that more than 2 mg/liter colistin combined with meropenem (2 g, 3-h infusion) was required to achieve the killing below the limit of detection (

17.
Mol Med Rep ; 19(1): 423-431, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30431100

RESUMO

The present study aimed to investigate the antifibrogenic effects of genistein (GEN) on the kidney in streptozotocin (STZ)­induced diabetic rats and to determine the associated mechanisms. Rats were randomized into four groups: Normal control (N), STZ (S), L (STZ + low­dose GEN) and H (STZ + high­dose GEN). After 8 weeks, the fasting blood glucose (FBG) level, the ratio of kidney weight to body weight (renal index), 24­h urine protein, blood urea nitrogen (BUN), serum creatinine (SCr), renal total antioxidant capacity (T­AOC), superoxide dismutase (SOD), lipid peroxidation (LPO), malondialdehyde (MDA) and hydroxyproline (Hyp) contents were measured. The histomorphology and ultrastructure of the kidney were also assessed. In addition, mRNA expression levels of transforming growth factor­ß1 (TGF­ß1) and protein expression levels of nuclear factor erythroid 2­related factor 2 (Nrf2), heme oxygenase­1 (HO­1), NAD(P)H:quinone oxidoreductase 1 (NQO1), TGF­ß1, mothers against decapentaplegic homolog 3 (Smad3), phosphorylated (p)­Smad3 and collagen IV were estimated. Compared with group N, the levels of FBG, renal index, 24­h urine protein, BUN, SCr, LPO, MDA and Hyp were increased, whereas the levels of T­AOC and SOD were decreased in group S. The structure of renal tissue was damaged, and the expression of Nrf2, HO­1 and NQO1 were reduced, whereas the expression of TGF­ß1, Smad3, p­Smad3 and collagen IV were increased in group S. Compared with group S, the aforementioned indices were improved in groups L and H. In conclusion, GEN exhibited reno­protective effects in diabetic rats and its mechanisms may be associated with the inhibition of oxidative stress by activating the Nrf2­HO­1/NQO1 pathway, and the alleviation of renal fibrosis by suppressing the TGF­ß1/Smad3 pathway.


Assuntos
Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Fibrose/tratamento farmacológico , Genisteína/farmacologia , Nefropatias/tratamento farmacológico , Estreptozocina/farmacologia , Animais , Nitrogênio da Ureia Sanguínea , Creatinina/metabolismo , Fibrose/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Nefropatias/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , NAD(P)H Desidrogenase (Quinona)/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Proteína Smad3/metabolismo , Superóxido Dismutase/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
18.
Genes Genomics ; 41(1): 125-131, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30255221

RESUMO

Mutations of Aristaless-related homeobox (ARX) gene were looked as the third cause of non-syndromic intellectual disability (NSID), while the boundary between true disease-causing mutations and non-disease-causing variants within this gene remains elusive. To investigate the relationship between ARX mutations and NSID, a panel comprising six reported causal mutations of the ARX was detected in 369 sporadic NSID patients and 550 random participants in Chinese. Two mutations, c.428_451 dup and p.G286S, may be disease-causing mutations for NSID, while p.Q163R and p.P353L showed a great predictive value in female NSID diagnosis with significant associations (X2 = 19.60, p = 9.54e-6 for p.Q163R; X2 = 25.70, p = 4.00e-07 for p.P353L), carriers of these mutations had an increased risk of NSID of more than fourfold. Detection of this panel also predicted significant associations between genetic variants of the ARX gene and NSID (p = 3.73e-4). The present study emphasized the higher genetic burden of the ARX gene on NSID in the Chinese population, molecular analysis of this gene should be considered for patients presenting NSID of unknown etiology.


Assuntos
Proteínas de Homeodomínio/genética , Deficiência Intelectual/genética , Mutação , Fatores de Transcrição/genética , Adolescente , China , Feminino , Humanos , Masculino , Polimorfismo Genético
19.
Front Microbiol ; 9: 2776, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30505298

RESUMO

Background: Polymyxins are a last-line class of antibiotics against multidrug-resistant Acinetobacter baumannii; however, polymyxin resistance can emerge with monotherapy. Therefore, synergistic combination therapy is a crucial strategy to reduce polymyxin resistance. Methods: This study conducted untargeted metabolomics to investigate metabolic responses of a multidrug-resistant (MDR) A. baumannii clinical isolate, AB090342, to colistin and aztreonam alone, and their combination at 1, 4, and 24 h. Metabolomics data were analyzed using univariate and multivariate statistics; metabolites showing ≥ 2-fold changes were subjected to bioinformatics analysis. Results: The synergistic action of colistin-aztreonam combination was initially driven by colistin via significant disruption of bacterial cell envelope, with decreased phospholipid and fatty acid levels at 1 h. Cell wall biosynthesis was inhibited at 4 and 24 h by aztreonam alone and the combination as shown by the decreased levels of two amino sugars, UDP-N-acetylglucosamine and UDP-N-acetylmuramate; these results suggested that aztreonam was primarily responsible for the synergistic killing at later time points. Moreover, aztreonam alone and the combination significantly depleted pentose phosphate pathway, amino acid, peptide and nucleotide metabolism, but elevated fatty acid and key phospholipid levels. Collectively, the combination synergy between colistin and aztreonam was mainly due to the inhibition of cell envelope biosynthesis via different metabolic perturbations. Conclusion: This metabolomics study is the first to elucidate multiple cellular pathways associated with the time-dependent synergistic action of colistin-aztreonam combination against MDR A. baumannii. Our results provide important mechanistic insights into optimizing synergistic colistin combinations in patients.

20.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 49(5): 706-711, 2018 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-30378330

RESUMO

OBJECTIVE: To investigate the effects of genistein (Gen) on myocardial injury in diabetic rats and explore its mechanisms. METHODS: Male SD rats were randomly divided into normal (N) group, diabetic (D) group, Gen 5 mg/kg treatment (L) group and Gen 25 mg/kg treatment (H) group (n=8 for each group). Intraperitoneal injection of streptozotocin was utilized to establish type 1 diabetic rat model. After successful building models, from the fifth week, the rats in the L and H groups were daily gavaged with 5 mg/kg and 25 mg/kg Gen solution, respectively. After 4 weeks of treatment with Gen, the hemodynamic parameters and fasting blood glucose (FBG) level were measured. The morphological structure and ultrastructure of myocardium were observed using HE staining and transmission electron microscopy, respectively. The levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), malondialdehyde (MDA), glutathione (GSH) and Caspase-3 in myocardial tissue were measured. The levels of myocardial Bcl-2 and Bax at mRNA expression were detected using RT-PCR. The levels of myocardial thioredoxin (Trx), Trx-interacting protein (TXNIP) and apoptosis signal regulating kinase 1 (ASK1) at protein expression were detected using Western blot. RESULTS: Compared with the N group, the FBG, TNF-α, IL-1ß, IL-6, MDA and Caspase-3 levels were increased (P<0.01), while hemodynamic parameters and GSH content were decreased (P<0.01), the myocardial morphological structure and ultrastructure were damaged in the D group. The levels of Bcl-2 mRNA and Trx protein expression were significantly decreased (P<0.01), while the levels of Bax mRNA, TXNIP and ASK1 protein expression were significantly increased (P<0.01) in the D group. Compared with the D group, in the L and H groups, there was no significant difference in [CM(155mm]FBG, the TNF-α, IL-1ß, IL-6, MDA and Caspase-3 levels were decreased (P<0.05, P<0.01), while the hemodynamic parameters and GSH content were increased (P<0.05, P<0.01); the myocardial morphological structural and ultrastructural damages were alleviated; the levels of Bcl-2 mRNA and Trx protein expression were increased (P<0.05, P<0.01), while the levels of Bax mRNA, TXNIP and ASK1 protein expression were significantly decreased (P<0.05, P<0.01). CONCLUSION: Gen exhibits a protective effect on myocardial injury in diabetic rats, and the mechanisms may be associated with the reduction of inflammatory reaction, the regulation of Trx system expression, and the inhibition of oxidative stress and cell apoptosis.


Assuntos
Cardiotônicos/farmacologia , Diabetes Mellitus Experimental/complicações , Genisteína/farmacologia , Coração/efeitos dos fármacos , Miocárdio/patologia , Animais , Apoptose , Proteínas de Transporte/metabolismo , Caspase 3/metabolismo , Proteínas de Ciclo Celular , Citocinas/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , MAP Quinase Quinase Quinase 5/metabolismo , Masculino , Miocárdio/ultraestrutura , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Estreptozocina , Tiorredoxinas/metabolismo , Proteína X Associada a bcl-2/metabolismo
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