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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 339-342, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027300

RESUMO

Abstract  The minimal residual disease (MRD) is the origin element that caused the relapse and drug resistance of hematological malignancies, the immune cells play a great role to clear MRD. A variety of immune cells have anti-tumor effects. However, tumor cells antagonize anti-tumor effects by reprogramming of constituents associated with tumor environment. Many different cell types, including immune cells, mesenchymal cells and tumor cells in tumor microenvironment release exosomes. The latest researches indicate that "cargo" and surface ligands carried by exosomes secreted by hematological malignant cells not only can affect the function of natural killer cell (migration, activation, proliferation, secretion and NKG2D expression), macrophage (migration and secretion) and dendritic cell (maturation and presentation), but also regulate the expression of PD-L1 and CCR2, CCL2 secretion and transformation of monocytes. The altered function of immune cells will eventually have effect on the progression of hematological malignancies.

2.
Sci Rep ; 10(1): 1611, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005912

RESUMO

According to the characteristics of complex spatial mode of long booster clustered launch vehicle, it is not suitable to derive the dynamic equations based on the simplified model of single beam considering only core rocket. In this paper, the long booster clustered launch-vehicle is simplified to a multi-beam model considering core and boosters. Then, due to the high proportion of the liquid propellant in the total mass of the launch vehicle, on the basis of the multi-beam model, a dynamic equation considering the elastic deformation and the liquid sloshing is established. The dynamic characteristics of the launch-vehicle and the interaction between liquid sloshing and aeroelasticity are studied by simulation. Based on the multi-beam model, the connection types between the core and the booster rocket are simplified to an elastic connection. The influence of the connection on the dynamic characteristics of the launch-vehicle is discussed. The results demonstrate that the multi-beam model can more fully reflect the dynamic characteristics of the long booster clustered launch-vehicle, and the connection form between the core and the boosters also has an important effect on the liquid sloshing and the elastic deformation.

3.
Virulence ; 11(1): 145-158, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32043433

RESUMO

Patients with Acinetobacter baumannii bacteremia treated with antipseudomonal cephalosporins showed higher 14-day mortality than patients treated with antipseudomonal carbapenems. We hypothesized that the bacterial membrane vesicles (BMVs) induced by antipseudomonal cephalosporins are more virulent than BMVs induced by antipseudomonal carbapenems.To simulate the clinical condition with inadequate antimicrobial treatment, carbapenem-resistant A. baumannii was treated with ceftazidime (an antipseudomonal cephalosporin) or imipenem (an antipseudomonal carbapenem) at 1/2 the minimum inhibitory concentration. BMVs and BMV-carried lipopolysaccharide were measured by nanoparticle tracking analysis and western blotting, respectively. Cytokine expression in RAW264.7 macrophages or mice serum induced by the BMVs was determined by ELISA, fluorescent bead-based immunoassay or western blotting. The virulence of the BMVs was assessed in mice. Liquid chromatography tandem-mass spectrometry was used to determine the protein contents of the BMVs.We found that ceftazidime induced a higher number of BMVs (CAZ-BMV), which carried more LPS, and induced higher expression levels of iNOS, IL-1ß, and IL-6 in macrophages, higher expression of many cytokines in mice, more neutrophil infiltration in lung interstitium, and higher mortality in mice than imipenem-induced BMVs (IMP-BMV). When adjusted to same amount of LPS, CAZ-BMV still led to higher mortality than IMP-BMV. Proteomic analysis revealed different protein contents in CAZ-BMV and IMP-BMV. In conclusion, A. baumannii BMVs induced by ceftazidime are more virulent than BMVs induced by imipenem.

4.
Mol Med ; 26(1): 11, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996122

RESUMO

PURPOSE: Genetic variants play a critical role in the development of breast cancer. This investigation aimed to explore the association between CASC16 polymorphisms and breast cancer susceptibility. METHODS: We conducted a case-control study of 681 patients and 680 healthy individuals to investigate the correlation of five SNPs with breast cancer in a Northwest Chinese female population. Odds ratios (OR) and 95% confidence intervals (CIs) were used to assess the association. RESULTS: Our study found that rs4784227 and rs12922061 were significantly related to an increased susceptibility to breast cancer (OR 1.22, p = 0.022; OR 1.21, p = 0.026). While rs3803662 was a protective role in breast cancer risk (OR 0.69, p = 0.042). Stratified analyses indicated that rs4784227 and rs12922061 would increase breast cancer susceptibility at age >  50 years. Rs3803662 was a reduced factor of breast cancer risk by age ≤ 50 years. Rs4784227 was significantly increased risk of breast cancer in stage III/IV. The rs45544231 and rs3112612 had a protective effect on breast cancer with tumor size > 2 cm. Rs4784227 and rs12922061 could enhance breast cancer risk in lymph node metastasis positive individuals. CASC16 rs12922061 and rs4784227 polymorphisms correlated with an increased risk of breast cancer in BMI >  24 kg/m2. Haplotype analyses revealed that Grs45544231 Trs12922061 Ars3112612 and Grs45544231 Crs12922061 Ars3112612 haplotypes decreased breast cancer risk. CONCLUSION: Our study revealed that CASC16 genetic variants were significantly related to breast cancer susceptibility, which might give scientific evidence for exploring the molecular mechanism of breast cancer.

5.
Inorg Chem ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31999111

RESUMO

A new family of Na3AgSnQ4 (Q = S or Se) and Na3MIIInS4 (MII = Cd or Hg) was successfully synthesized in vacuum-sealed silica tubes for the first time. They exhibit similar isolated one-dimensional (1D) double chains {[AgSnQ4]n vs [(MII/In)S4]n} in their structures. After the detailed survey on the Inorganic Crystal Structure Database, title compounds can be described as the first discovered examples exhibiting novel 1D double-chain configurations in the known 171 (MIB and MIVA) or 48 (MIIB and MIIIA) element-based quaternary A-MIB/MIIB-MIVA/MIIIA-Q chalcogenides. In addition, their dimensionalities on the mode of connection between two anionic groups are closely related to the empirical A/(IB+IVA) and A/(IIB+IIIA) in the unit cell or the (IB+IVA)/Q and (IIB+IIIA)/Q ratios, which may produce a good way to predict and design new chalcogenides with low-dimensional structures. Photoluminescence measurement shows that Na3CdGaS4 and Na3CdInS4 display strong red emission (648 and 647 nm) at room temperature that also agrees well with the change in color from yellow to red under the irradiation of an ultraviolet lamp. Moreover, all of the title crystals exhibit a large optical anisotropy (Δn@1064 nm ≥ 0.13), and isolated 1D double chains may produce a huge effect to enhance optical anisotropy based on the first-principles calculations, which also gives us a feasible way to design new birefringent materials.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31958309

RESUMO

OBJECTIVE: Diabetic nephropathy (DN) and diabetic retinopathy (DR) comprise major microvascular complications of diabetes that occur with a high concordance rate in patients and are considered to potentially share pathogeneses. In this case-control study, we sought to investigate whether DR-related single nucleotide polymorphisms (SNPs) exert pleiotropic effects on renal function outcomes among patients with diabetes. RESEARCH DESIGN AND METHODS: A total of 33 DR-related SNPs were identified by replicating published SNPs and via a genome-wide association study. Furthermore, we assessed the cumulative effects by creating a weighted genetic risk score and evaluated the discriminatory and prediction ability of these genetic variants using DN cases according to estimated glomerular filtration rate (eGFR) status along with a cohort with early renal functional decline (ERFD). RESULTS: Multivariate logistic regression models revealed that the DR-related SNPs afforded no individual or cumulative genetic effect on the nephropathy risk, eGFR status or ERFD outcome among patients with type two diabetes in Taiwan. CONCLUSION: Our findings indicate that larger studies would be necessary to clearly ascertain the effects of individual genetic variants and further investigation is also required to identify other genetic pathways underlying DN.

7.
Theranostics ; 10(1): 17-35, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31903103

RESUMO

Approximately 10% of bone fractures do not heal satisfactorily, leading to significant clinical and socioeconomic implications. Recently, the role of macrophages in regulating bone marrow stem cell (BMSC) differentiation through the osteogenic pathway during fracture healing has attracted much attention. Methods: The tibial monocortical defect model was employed to determine the critical role of macrophage scavenger receptor 1 (MSR1) during intramembranous ossification (IO) in vivo. The potential functions and mechanisms of MSR1 were explored in a co-culture system of bone marrow-derived macrophages (BMDMs), RAW264.7 cells, and BMSCs using qPCR, Western blotting, immunofluorescence, and RNA sequencing. Results: In this study, using the tibial monocortical defect model, we observed delayed IO in MSR1 knockout (KO) mice compared to MSR1 wild-type (WT) mice. Furthermore, macrophage MSR1 mediated PI3K/AKT/GSK3ß/ß-catenin signaling increased ability to promote osteogenic differentiation of BMSCs in the co-culture system. We also identified proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) as the target gene for macrophage MSR1-activated PI3K/AKT/GSK3ß/ß-catenin pathway in the co-culture system that facilitated M2-like polarization by enhancing mitochondrial oxidative phosphorylation. Conclusion: Our findings revealed a previously unrecognized function of MSR1 in macrophages during fracture repair. Targeting MSR1 might, therefore, be a new therapeutic strategy for fracture repair.

8.
Carbohydr Polym ; 230: 115619, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31887868

RESUMO

An efficient, ecofriendly, amide-functionalized cellulose-based porous adsorbent was synthesized by a cross-linking reaction between cellulose filament fibers and bisacrylamide at room temperature. This process is simple, fast and inexpensive, and has significant potential for industrial applications. The prepared material has numerous adsorption sites, resulting in the highly efficient removal of anionic dyes and copper ions from aqueous media. The maximum adsorption capacities of this cellulose-based adsorbent for the dyes Acid Black 1 and Acid Red 18 and for copper ions were 751.8, 417.9, and 51.3 mg g-1, respectively. Regeneration experiments showed that the removal efficiencies for all model pollutants remained above 92 % after five consecutive recycling trials. These results indicate that amide-functionalized cellulose-based adsorbents could possibly be used to treat industrial wastewaters.

9.
Sex Transm Infect ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31911426

RESUMO

OBJECTIVES: Our objective was to determine the impact of maternal HIV-hepatitis B virus (HBV) coinfection on pregnancy outcomes. METHODS: The current study was conducted in a county of Yi Autonomous Prefecture in southwest China. Data were abstracted from hospitalisation records, including maternal and infant information. The seroprevalences of HIV and HBV infections and HIV-HBV coinfection were determined and the impact of maternal HIV-HBV coinfection on adverse pregnancy outcomes was assessed using logistic regression analysis. A treatment effects linear regression model was also applied to examine the effect of HBV, HIV or coinfection to quantify the absolute difference in birth weight from a reference of HBV-HIV negative participants. RESULTS: A total of 13 198 pregnant women were included in our study, and among them, 99.1% were Yi people and 90.8% lived in rural area. The seroprevalences of HIV and HBV infections and HIV-HBV coinfection were 3.6% (95% CI: 3.2% to 3.9%), 3.2% (95% CI: 2.9% to 3.5%) and 0.2% (95% CI: 0.1% to 0.2%) among the pregnant women, respectively. Maternal HIV-HBV coinfection was a risk factor for low birth weight (adjusted OR (aOR)=5.52, 95% CI: 1.97 to 15.40). Compared with the HIV mono-infection group, the risk of low birth weight was significantly higher in the HIV-HBV coinfection group (aOR=3.62, 95% CI: 1.24 to 10.56). Maternal HIV infection was associated with an increased risk of low birth weight (aOR=1.90, 95% CI: 1.38 to 2.60) and preterm delivery (aOR=2.84, 95% CI: 1.81 to 4.47). Perinatal death was more common when mothers were infected with HBV (aOR=2.85, 95% CI: 1.54 to 5.26). CONCLUSIONS: The prevalence of HIV infection was high among pregnant women of the Yi region. Both HIV and HBV infections might have adverse effects on pregnancy outcomes. Maternal HIV-HBV coinfection might be a risk factor for low birth weight in the Yi region, which needs to be confirmed.

10.
Fitoterapia ; 140: 104422, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31756377

RESUMO

Peniterester (1), a new tricyclic sesquiterpene, together with 6 known compounds (2-7) were isolated from the secondary metabolites of an artificial mutant Penicillium sp. T2-M20 which was obtained from the parental strain Penicillium sp. T2-8 via UV irradiation as well as nitrosoguanidine (NTG) induction. Peniterester was only produced by the mutant T2-M20 on the basis of LC-MS analysis. Meanwhile, the results of in vitro bioactivities screening indicated that peniterester owned obvious antibacterial activities against Bacillus subtilis, Escherichia coli and Staphylococcus aureus with MICs of 8.0, 8.0 and 4.0 µg/mL, respectively.


Assuntos
Antibacterianos/farmacologia , Penicillium/química , Sesquiterpenos/farmacologia , Antibacterianos/isolamento & purificação , Bacillus subtilis/efeitos dos fármacos , Linhagem Celular Tumoral , China , Escherichia coli/efeitos dos fármacos , Gastrodia/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Rizoma/microbiologia , Metabolismo Secundário , Sesquiterpenos/isolamento & purificação , Staphylococcus aureus/efeitos dos fármacos
11.
Biochem Biophys Res Commun ; 522(4): 889-896, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-31806368

RESUMO

Upon invading the cell, the viral RNA is recognized by the RIG-I receptor located in the cytoplasm, causing the RIG-I receptor to be activated. The activated RIG-I receptor transmits downstream antiviral signals by interacting with the adaptor protein VISA located on the mitochondria, leading to the production of type Ⅰ interferons and crude inflammatory cytokine genes. Although there have been many studies on antiviral signal transduction of RIG-I receptors in recent years, the mechanism of RIG-I-VISA-mediated antiviral regulation is still not fully understood. In this study, we identified SNX5 as a negative regulator of RLR-mediated antiviral signaling. Our results show that overexpression of SNX5 inhibits viral-induced activation of the IFN-ß promoter, ISRE, NF-κB, and IRF3, whereas RNAi knockdown of SNX5 expression shows opposite results. We also found that overexpression of SNX5 enhanced RIG-I's K48 ubiquitination and attenuated its K63 ubiquitination, resulting in inhibition of virus-induced RIG-I expression. Besides, further studies show that SNX5 overexpression weakens the interaction between VISA and TRAF2/5. Our findings suggest that SNX5 negatively regulates RLR-mediated antiviral signaling by targeting the RIG-I-VISA signalosome and provide new evidence for the negative regulation of RIG-I-mediated innate immune response mechanisms.

12.
Hypertens Res ; 43(2): 140-147, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31666712

RESUMO

Some studies have shown that a higher ideal cardiovascular health score (CVHS) predicts a lower incidence of arterial stiffness. Few studies have used multiple measurements of CVHS to examine the impact of CVHS on arterial stiffness. The current study aimed to identify the long-term patterns in CVHS trajectory and to explore the association between CVHS trajectory and arterial stiffness. The study cohort consisted of 18,854 participants from the Kailuan Study who were followed up for five physical examinations over 8.10 years. Five discrete CVHS trajectories were identified among the participants: low-stable (8.10%), low-moderate (6.84%), moderate-low (23.46%), moderate-stable (39.83%), and elevated-stable (21.77%). After adjustment for confounding factors, generalized linear model analysis showed that CVHS trajectory group correlated negatively with brachial-ankle pulse wave velocity (baPWV). Compared with the low-stable group, the low-moderate group, moderate-low group, moderate-stable group, and elevated-stable group had B values of -41.81, -24.11, -86.79, and -169.54, respectively. We also used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for CVHS trajectory groups and arterial stiffness. In fully adjusted models, ORs were 0.76 (95% CI: 0.62-0.94) for the low-moderate group, 0.80 (95% CI: 0.67-0.97) for the moderate-low group, 0.51 (95% CI: 0.42-0.62) for the moderate-stable group, and 0.23 (95% CI: 0.18-0.29) for the elevated-stable group compared with the low-stable group. The results were consistent across a number of sensitivity analyses. In conclusion, the higher long-term attainment and the improvement of CVHS were negatively associated with baPWV and could reduce the risk of arterial stiffness. Our study emphasizes the importance of optimizing CVH throughout life to prevent the incidence of arterial stiffness.

13.
J Sci Food Agric ; 100(3): 1064-1071, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31713870

RESUMO

BACKGROUND: Glucosinolates (GSLs) are secondary metabolites, mainly existing in Brassica vegetables. Their breakdown products have health benefits and contribute to the distinctive taste of these vegetables. Because of their high value, there is a lot of interest in developing breeding strategies to increase the content of beneficial GSLs in Brassica species. GSLs are synthesized from certain amino acids and their biological roles depend largely on the structure of their side chains. Flavin-containing monooxygenase (FMOGS-OX ) genes are involved in the synthesis of these side chains. To better understand GSL biosynthesis, we sequenced the transcriptomes of turnip (Brassica rapa var. rapa) tubers at four developmental stages (S1-S4) and determined their GSL content. RESULTS: The total GSL content was high at the early stage (S1) of tuber development and increased up to S3, then decreased at S4. We detected 61 differentially expressed genes, including five FMOGS-OX genes, that were related for GSL biosynthesis among the four developmental stages. Most of these genes were highly expressed at stages S1 to S3, but their expression was much lower at S4. We estimated the effect of the five FMOGS-OX genes on GSL content by overexpressing them in turnip hairy roots and found that the amount of aliphatic GSLs increased significantly in the transgenic plants. CONCLUSION: The transcriptome data and characterization of genes involved in GSL biosynthesis, particularly the FMOGS-OX genes, will be valuable for improving the yield of beneficial GSLs in turnip and other Brassica crops. © 2019 Society of Chemical Industry.


Assuntos
Brassica rapa/enzimologia , Brassica rapa/crescimento & desenvolvimento , Glucosinolatos/biossíntese , Oxigenases de Função Mista/metabolismo , Proteínas de Plantas/metabolismo , Vias Biossintéticas , Brassica rapa/genética , Brassica rapa/metabolismo , Dinitrocresóis/metabolismo , Regulação da Expressão Gênica de Plantas , Oxigenases de Função Mista/genética , Proteínas de Plantas/genética , Raízes de Plantas/enzimologia , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Plantas Geneticamente Modificadas/enzimologia , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/metabolismo , Transcriptoma
14.
J Asian Nat Prod Res ; 22(1): 24-29, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31368354

RESUMO

Two new naturally occurring products named salviamine G (1) and 4-methyl-9-(ethoxycarbonyl)-8-naphthoic acid (2) were isolated from the rhizomes of Salvia miltiorrhiza. Their structures were elucidated using spectroscopic data (UV, IR, HRESIMS, 1D and 2D NMR). Compounds 1 and 2 were screened for their inhibitory activity against HSV-1 and influenza A (H3N2) using acyclovir (ACV, IC50 = 0.67 µM) and oseltamivir (IC50 = 2.01 µM) as a positive control. Compound 1 exhibited moderate inhibitory activity against HSV-1 and influenza A (H3N2) with IC50 values of 11.11 and 8.62 µM, respectively.

15.
J Asian Nat Prod Res ; 22(1): 17-23, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31389260

RESUMO

Two new isobenzofuranone derivatives, polyphthaliside A (1) and polyphthaliside B (2), and a new isocoumarin derivative, polyisocoumarin (3), were isolated from Polygonum cuspidatum. Their structures were elucidated by detailed spectroscopic analysis and chemical methods. The cytotoxicity activity and PTP1B inhibitory activity of compounds 1-3 were estimated and none of them exhibited activities at a concentration of 10 µM.

16.
Sci Total Environ ; 708: 134441, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31796293

RESUMO

We investigated the tidal variability of polycyclic aromatic hydrocarbons (PAHs) and organophosphate esters (OPEs) in water dissolved phase from a coastal area of Dalian, China, as well as their air-water exchange trends. The concentrations of PAHs and OPEs in water were in the range of 50.5-74.7 ng/L and 21.6-61.5 ng/L, respectively. Phenanthrene (PHE) was the dominant congener followed by fluorene (FLU) for PAHs, while tris(2-chloroisopropyl) phosphate (TCIPP) and tris(2-chloroethyl) phosphate (TCEP) dominated for OPEs. PAHs in coastal water showed a tidal variability, but not for OPEs, which may due to the influence of occasional wastewater discharges of OPEs. The source apportionments using principle component analysis and positive matrix factorization suggested that PAHs in the coastal water mainly came from oil spill from ships, coal combustion, and petroleum combustion, while OPEs were derived from diverse sources. The fugacity fractions (ff) suggested that ACY, ACE, FLU, PHE, TCEP, and TPHP volatilized from water into air, while TNBP, TCIPP, and TDCIPP deposited from air into water, and FLA, PYR, BaA, CHR, and EHDPP reached equilibrium. The ff values varied slightly with tidal circle, but the variations were not enough to alter the air-water exchange directions of those compounds. Although the influences of tide on the air-water exchange of PAHs and OPEs were limited, tide still played an important role on the transports and diffusions of those chemicals in the coastal water, which requires further studies.

17.
Bioorg Chem ; 95: 103503, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31855825

RESUMO

An investigation of a co-culture of the Armillaria sp. and endophytic fungus Epicoccum sp. YUD17002 associated with Gastrodia elata led to the isolation of eight new compounds, including five protoilludane-type sesquiterpenes (1-5) and three aryl esters (6-8), together with six known analogues (9-14). The assignments of their structures were conducted via extensive analyses of the spectroscopic data and comparison of experimental and calculatedelectronic circular dichroism(ECD)data. Notably, these new compounds were not present in the pure culture controls and were only detected in the co-cultures. Compound 4 is the first example of an ent-protoilludane sesquiterpenoid scaffold bearing a five-membered lactone. Compound 6 exhibited moderate in vitro cytotoxic activities against five human cancer cell lines (HL-60, A549, MCF-7, SMMC-7721, and SW480) with IC50 values ranging from 15.80 to 23.03 µM. Moreover, 6 showed weak acetylcholinesterase inhibitory activity (IC50 value of 23.85 µM).

18.
J Neurochem ; : e14939, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31821563

RESUMO

N-methyl-D-aspartate (NMDA) receptor channels are activated by glutamate (or NMDA) and glycine. The channels also undergo desensitization, which denotes decreased channel availability, after prolonged exposure to the activating ligands. Glycine apparently has a paradoxical negative effect on desensitization, as the increase in ambient glycine in concentrations required for channel activation would increase sustained NMDA receptor currents. We hypothesized that this classical "glycine-dependent desensitization" could be glycine-dependent activation in essence. By performing electrophysiological recordings and biophysical analyses with rat brain NMDA receptors heterogeneously expressed in Xenopus laevis oocytes, we characterized that the channel opened by "only" NMDA (in nominally glycine-free condition probably with the inevitable nanomolar glycine) would undergo a novel form of deactivation rather than desensitization, and is thus fully available for subsequent activation. Moreover, external tetrapentylammonium ions (TPentA), tetrabutylammonium ions, and tetrapropylammonium ions (TPA, in higher concentrations) block the pore and prohibit channel desensitization with a simple "foot-in-the-door" hindrance effect. TpentA and TPA have the same voltage dependence but show different flow dependence in binding affinity, revealing a common binding site at an electrical distance of ~0.7 from the outside yet differential involvement of the flux-coupling region in the external pore mouth. The smaller tetraethylammonium ion and the larger tetrahexylammonium and tetraheptylammonium ions may block the channel but could not affect desensitization. We conclude that NMDA receptor desensitization requires concomitant binding of both glycine and glutamate, and thus movement of both GluN1 and GluN2 subunits. Desensitization gate itself embodies a highly restricted pore reduction with a physical distance of ~4 Å from the charged nitrogen atom of bound tetraalkylammonium ions, and is located very close to the activation gate in the bundle-crossing region in the external pore vestibule.

19.
Artigo em Inglês | MEDLINE | ID: mdl-31789951

RESUMO

BACKGROUND: Glioma is associated with high recurrence and poor survival, despite the success of tumor resection surgery. This may be partly because the immune microenvironment within a glioma is susceptible to perioperative immunosuppression. Therefore, intraoperative anesthesia-related immunomodulators, such as scalp block, intravenous anesthesia, the opioid dosage administered, and transfusions, may influence oncological outcomes among patients with glioma. The aim of this retrospective study was to investigate the influence of anesthetic techniques on oncological outcomes after craniotomy for glioma resection, particularly the effects of scalp block, intravenous anesthesia, and inhalation anesthesia. METHODS: Consecutive patients who underwent primary glioma resection surgeries between January 2010 and December 2017 were analyzed to compare postcraniotomy oncological outcomes (progression-free survival [PFS] and overall survival) by using the Kaplan-Meier method and multivariate Cox regression analysis. A propensity score-matched regression analysis including prognostic covariates was also conducted to analyze the selected relevant anesthetic factors of the unmatched regression model. RESULTS: A total of 230 patients were included in the final analysis. No analyzed anesthetic factor was associated with overall survival. Patients who received scalp block had a more favorable median (95% confidence interval [CI]) PFS (55.37 [95% CI, 12.63-62.23] vs. 14.07 [95% CI, 11.27-17.67] mo; P=0.0053). Scalp block was associated with improved PFS before (hazard ratio, 0.465; 95% CI, 0.272-0.794; P=0.0050) and after (hazard ratio, 0.367; 95% CI, 0.173-0.779; P=0.0091) propensity score-matched Cox regression analysis. By contrast, intravenous anesthesia, amount of opioid consumed, and transfusion were not associated with PFS. CONCLUSIONS: The study results suggest that the scalp block improves the recurrence profiles of patients receiving primary glioma resection.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31832182

RESUMO

Purpose: Treatment of chronic osteomyelitis (bone infection) remains a clinical challenge. Our previous study had demonstrated that NEMO-binding domain (NBD) peptide effectively ameliorates the inhibition of osteoblast differentiation by TNF-α in vitro. In this work, NBD peptide was evaluated in vivo for treating chronic osteomyelitis induced by methicillin-resistant Staphylococcus aureus (MRSA) in a rabbit model. Methods: Tibial osteomyelitis was induced in 50 New Zealand white rabbits by tibial canal inoculation of MRSA strain. After 3 weeks, 45 rabbits with osteomyelitis were randomly divided into four groups that correspondingly received the following interventions: 1) Control group (9 rabbits, no treatment); 2) Van group (12 rabbits, debridement and parenteral treatment with vancomycin); 3) NBD + Van group (12 rabbits, debridement and local NBD peptide injection, plus parenteral treatment with vancomycin); 4) NBD group (12 rabbits, debridement and local NBD peptide injection). Blood samples were collected weekly for the measurement of leucocyte count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels. The rabbits in all four groups were sacrificed 6 weeks after debridement; the anti-infective efficacy was evaluated by radiological, histological, and microbiological examination, and promotion of bone remodeling was quantified by micro-CT using the newly formed bone. Results: Except two rabbits in the Control group and one in the NBD group that died from severe infection before the end point, the remaining 42 animals (7, 12, 12, 11 in the Control, Van, NBD + Van, and NBD group respectively) were sacrificed 6 weeks after debridement. In general, there was no significant difference in the leucocyte count, and ESR and CRP levels, although there were fluctuations throughout the follow-up period after debridement. MRSA was still detectable in bone tissue samples of all animals. Interestingly, treatment with NBD peptide plus vancomycin significantly reduced radiological and histological severity scores compared to that in other groups. The best therapeutic efficacy in bone defect repair was observed in the NBD peptide + Van group. Conclusions: In a model of osteomyelitis induced by MRSA, despite the failure in demonstrating antibacterial effectiveness of NBD peptide in vivo, the results suggest antibiotics in conjunction with NBD peptide to possibly have promising therapeutic potential in osteomyelitis.

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