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1.
Food Chem ; 367: 130700, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34352694

RESUMO

Present study prepared curcumin-loaded nanoliposomes using bovine milk, krill phospholipids and cholesterol; and investigated the effects of cholesterol on membrane characteristics, storage stability and antibacterial properties of the curcumin nanoliposomes. Bovine milk phospholipids which have higher saturation than krill phospholipids resulted in formation of curcumin-loaded nanoliposomes with higher encapsulation efficiency (84.78%), larger absolute value of zeta potential and vesicle size (size: 159.15 ± 5.27 nm, zeta potential: -28.3 ± 0.62 mV). Cholesterol helps to formation of a more hydrophobic, compact and tighter bilayer membrane structure which improved the storage stability of nanoliposomes under alkaline (66.25 ± 0.46%), heat (43.25 ± 0.69%) and sunlight (49.44 ± 1.78%) conditions. In addition, curcumin-loaded nanoliposomes can effectively target infectious bacteria which secrete pore-forming toxins such as Staphylococcus aureus by causing the bacterial cell wall to lysis. Findings from present work can guide future development of novel antibacterial agents for use in food preservation.


Assuntos
Curcumina , Fosfolipídeos , Animais , Antibacterianos , Bovinos , Colesterol , Lipossomos , Leite , Tamanho da Partícula
3.
Mol Pharm ; 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34723557

RESUMO

Artemisinin (ART) is a most promising antimalarial agent, which is both effective and well tolerated in patients, though it has therapeutic limitations due to its low solubility, bioavailability, and short half-life. The objective of this work was to explore the possibility of formulating ART cocrystals, i.e., artemisinin-orcinol (ART-ORC) and artemisinin-resorcinol (ART2-RES), as oral dosage forms to deliver ART molecules for bioavailability enhancement. This is the first part of the study, aiming to develop a simple and effective formulation, which can then be tested on an appropriate animal model (i.e., mouse selected for in vivo study) to evaluate their preclinical pharmacokinetics for further development. In the current work, the physicochemical properties (i.e., solubility and dissolution rate) of ART cocrystals were measured to collect information necessary for the formulation development strategy. It was found that the ART solubility can be increased significantly by its cocrystals, i.e., 26-fold by ART-ORC and 21-fold by ART2-RES, respectively. Screening a set of polymers widely used in pharmaceutical products, including poly(vinylpyrrolidone), hydroxypropyl methylcellulose, and hydroxypropyl methylcellulose acetate succinate, based on the powder dissolution performance parameter analysis, revealed that poly(vinylpyrrolidone)/vinyl acetate (PVP-VA) was the most effective crystallization inhibitor. The optimal concentration of PVP-VA at 0.05 mg/mL for the formulation was then determined by a dissolution/permeability method, which represented a simplified permeation model to simultaneously evaluate the effects of a crystallization inhibitor on the dissolution and permeation performance of ART cocrystals. Furthermore, experiments, including surface dissolution of single ART cocrystals monitored by Raman spectroscopy, scanning electron microscopy and diffusion properties of ART in solution measured by 1H and diffusion-ordered spectroscopy nuclear magnetic resonance spectroscopy, provided insights into how the excipient affects the ART cocrystal dissolution performance and bioavailability.

4.
Phys Rev Lett ; 127(16): 166802, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34723600

RESUMO

Layers of two-dimensional materials stacked with a small twist angle give rise to beating periodic patterns on a scale much larger than the original lattice, referred to as a "moiré superlattice." Here, we demonstrate a higher-order "moiré of moiré" superlattice in twisted trilayer graphene with two consecutive small twist angles. We report correlated insulating states near the half filling of the moiré of moiré superlattice at an extremely low carrier density (∼10^{10} cm^{-2}), near which we also report a zero-resistance transport behavior typically expected in a 2D superconductor. The full-occupancy (ν=-4 and ν=4) states are semimetallic and gapless, distinct from the twisted bilayer systems.

5.
Neuropharmacology ; 203: 108881, 2021 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-34785162

RESUMO

Although serotonin 1A (5-HT1A) receptor agonists are widely used as the additive compound to reduce l-dopa-induced dyskinesia in Parkinson's disease (PD), few studies focused on the effect and mechanism of 5-HT1A receptor agonist on the motor symptoms of PD. Unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats were used and implantation of electrodes was performed in the motor cortex of these rats. So the effect of 5-HT1A receptor agonist 8-OH-DPAT on motor behaviors and oscillatory activities were evaluated. In addition, 8-OH-DPAT combined with D2 receptor antagonist raclopride, NMDA receptor antagonist MK-801, or its agonist d-cycloserine (DCS) were co-administrated. 8-OH-DPAT administration significantly improved spontaneous locomotor activity and asymmetric forepaw function in 6-OHDA-lesioned rats. Meanwhile, 8-OH-DPAT identified selective modulation of the abnormal high beta oscillations (25-40 Hz) in the motor cortex of 6-OHDA-lesioned rats, without inducing pathological finely tuned gamma around 80 Hz. Different from 8-OH-DPAT, l-dopa treatment produced a prolonged improvement on motor performances and differential regulation of high beta and gamma oscillations. However, dopamine D2 receptor antagonist had no influence on the 8-OH-DPAT-mediated-motor behaviors and beta oscillations in 6-OHDA-lesioned rats. In contrast, subthreshold NMDA receptor antagonist MK-801 obviously elevated the 8-OH-DPAT-mediated-motor behaviors, while NMDA receptor agonist DCS partially impaired the 8-OH-DPAT-mediated symptoms in 6-OHDA-lesioned rats. This study suggests that 5-HT1A receptor agonist 8-OH-DPAT improves motor activity and modulates the oscillations in the motor cortex of parkinsonian rats. Different from l-dopa, 8-OH-DPAT administration ameliorates motor symptoms of PD through glutamatergic rather than the dopaminergic pathway.

6.
Cell Death Dis ; 12(11): 1070, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34759263

RESUMO

Uncontrolled overactivation of autophagy may lead to autophagic cell death, suppression of which is a pro-survival strategy for tumors. However, mechanisms involving key regulators in modulating autophagic cell death remain poorly defined. Here, we report a novel long noncoding RNA, p53 upregulated regulator of p53 levels (PURPL), functions as an oncogene to promote cell proliferation, colony formation, migration, invasiveness, and inhibits cell death in melanoma cells. Mechanistic studies showed that PURPL promoted mTOR-mediated ULK1 phosphorylation at Ser757 by physical interacting with mTOR and ULK1 to constrain autophagic response to avoid cell death. Loss of PURPL led to AMPK-mediated phosphorylation of ULK1 at Ser555 and Ser317 to over-activate autophagy and induce autophagic cell death. Our results identify PURPL as a key regulator to modulate the activity of autophagy initiation factor ULK1 to repress autophagic cell death in melanoma and may represent a potential intervention target for melanoma therapy.

7.
Front Cardiovasc Med ; 8: 726516, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778396

RESUMO

Objective: To explore the application of the Cox model based on extreme learning machine in the survival analysis of patients with chronic heart failure. Methods: The medical records of 5,279 inpatients diagnosed with chronic heart failure in two grade 3 and first-class hospitals in Taiyuan from 2014 to 2019 were collected; with death as the outcome and after the feature selection, the Lasso Cox, random survival forest (RSF), and the Cox model based on extreme learning machine (ELM Cox) were constructed for survival analysis and prediction; the prediction performance of the three models was explored based on simulated data with three censoring ratios of 25, 50, and 75%. Results: Simulation results showed that the prediction performance of the three models decreased with increasing censoring proportion, and the ELM Cox model performed best overall; the ELM Cox model constructed with 21 highly influential survival predictors screened from actual chronic heart failure data showed the best performance with C-index and Integrated Brier Score (IBS) of 0.775(0.755, 0.802) and 0.166(0.150, 0.182), respectively. Conclusion: The ELM Cox model showed good discrimination performance in the survival analysis of patients with chronic heart failure; it performs consistently for data with a high proportion of censored survival time; therefore, the model could help physicians identify patients at high risk of poor prognosis and target therapeutic measures to patients as early as possible.

8.
Colloids Surf B Biointerfaces ; 209(Pt 2): 112175, 2021 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-34740095

RESUMO

Topical use of antimicrobial agents to treat wounds to inhibit bacterial invasion and facilitate wound healing is an effective strategy. In this work, an antibacterial xerogel film for potential applications in wound dressings was developed. First, a natural antibacterial agent, quercetin (Qu), was made into water-soluble quercetin-borate (QuB) nanoparticles by merging a solvent exchange method with the borate esterification reaction. QuB nanoparticles were then employed as the cross-linking agent to achieve gelation of poly(vinyl alcohol) (PVA) to obtain antimicrobial QuB-PVA composite microgels. Furthermore, QuB-PVA microgels were utilized as raw materials to produce xerogel films via an electrospray technique. The as-prepared QuB-PVA xerogel films exhibited excellent bacteriostasis, antioxidation, biocompatibility, self-healing, accelerated skin regeneration and functional restoration, and promoted skin wound healing. The QuB-PVA films significantly facilitated the in vivo healing speed of full-thickness skin wounds compared to commercial dressings. We believe that the present multifunctional QuB-PVA xerogel film is an excellent candidate for the wound dressings.

9.
J Hazard Mater ; 424(Pt C): 127352, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34740157

RESUMO

In this study, two parallel-operated expanded granular sludge bed (EGSB) reactors, one used to treat oxytetracycline (OTC) manufacturing wastewater with gradual increase of OTC concentration as experimental reactor and the other fed with the same wastewater without OTC as control reactor, were operated to investigate the behavior of antibiotics resistance genes (ARGs) and mobile genetic elements (MGEs) and their possible relationships with bacterial community among influent, sludge and effluent environments. Though the average absolute abundance of ARGs slightly decreased (0.26 - log), the ARGs' relative abundance normalized to 16S-rRNA gene copy numbers showed a significant upward trend in effluent (2 multiples - increase) and the absolute and relative abundances both extremely increased in anaerobic sludge, indicating that anaerobic treatment process cannot reduce ARGs efficiently, inversely can increase the risk of ARGs through the proliferation of antibiotics resistance bacteria (ARB) under the suppression of OTC. MGEs, bacterial communities and OTC concentration mainly impacted the ARGs profiles, which contributed 88.4% to the variation of ARGs. The differences and correlations of hosts in influent, effluent and sludge were further confirmed by network analysis. Overall, this study enhanced the understanding of the prevalence and transfer of ARGs in OTC production effluents during anaerobic treatment.

10.
Opt Express ; 29(21): 34510-34521, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34809239

RESUMO

Terahertz (THz) frequency modulated continuous wave (FMCW) technology is a means of nondestructive testing. The signal's nonlinearity is an unavoidable problem in the daily application of THz FMCW technology. The signal's nonlinearity will lead to the spectrum broadening of the FMCW's beat frequency (BF) signal, which degrades the range resolution and result in distance-measuring error. Traditional methods require additional hardware or require a lot of computation, which are not conducive to the miniaturization of the system and real-time measurement. A novel method for correcting the nonlinear error of THz FMCW technology has been proposed and demonstrated in this article. In the proposed method, the windowed Fourier transform (WFT) is introduced to estimate the BF corresponding to the measured target, according to the linearity distribution of voltage-controlled oscillator (VCO). In this way, the measured target's BF can be accurately estimated from the unprocessed BF signal with a poor linearity. From the estimated BF of the reference target, the non-linear compensation coefficients are calculated. With the non-linear compensation coefficients, the non-linearity of the output BF signal can be calibrated. The results of simulations and experiments show that the proposed method allows the range resolution of an FMCW system to reach the theoretical limit.

11.
BMC Neurol ; 21(1): 460, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34814870

RESUMO

BACKGROUND: The aim of this study was to investigate the relationship between tumor biology and values of cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), time to peak (TTP), permeability surface (PS) of tumor in patients with glioma. METHODS: Forty-six patients with glioma were involved in the study. Histopathologic and molecular pathology diagnoses were obtained by tumor resection, and all patients accepted perfusion computed tomography (PCT) before operation. Regions of interests were placed manually at tumor and contralateral normal-appearing thalamus. The parameters of tumor were divided by those of contralateral normal-appearing thalamus to normalize at tumor (relative [r] CBV, rCBF, rMTT, rTTP, rPS). The relationships of the parameters, world health organization (WHO) grade, molecular pathological findings were analysed. RESULTS: The rCBV, rMTT and rPS of patients are positively related to the pathological classification (P < 0.05). The values of rCBV and rPS in IDH mutated patients were lower than those IDH wild-type. The values of rCBF in patients with MGMT methylation were lower than those MGMT unmethylation (P < 0.05). The MVD of TERT wild-type group was lower than TERT mutated group (P < 0.05). The values of rCBV were significant difference in the four molecular groups divided by the combined IDH/TERT classification (P < 0.05). The progression free survival (PFS) and overall survival (OS) were significant difference in the four molecular groups divided by the combined IDH/TERT classification (P < 0.05). CONCLUSIONS: Our study introduces and supports the changes of glioma flow perfusion may be closely related to its biological characteristics.

12.
Can J Gastroenterol Hepatol ; 2021: 5545181, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805027

RESUMO

Objective: To identify markers that predict the progression to hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). Methods: We recruited 125 patients with chronic hepatitis B (CHB) between September 2013 and March 2017. During hospitalization, 25 patients progressed to LF and were classified as the LF group, while the remaining 100 patients were classified as the non-LF (NLF) group. We compared the kinetic changes in clinical and immune indicators including age, total bilirubin level, prothrombin time, model for end-stage liver disease score, interleukin (IL)-6, IL-8, and IL-10 cytokine levels, and number of T helper 17 and regulatory T cells between groups to determine their association with progression to HBV-ACLF. The prognostic value of clinical and immune indicators was determined using the area under the receiver operating characteristic curve (AUC) value. Results: Cox regression analysis suggested that the plasma IL-6 level could predict CHB progression to HBV-ACLF (relative risk = 1.082, 95% confidence interval: 1.006-1.164; P=0.034). The AUC value, sensitivity, and specificity of baseline IL-6 level for predicting HBV-ACLF were 82.63%, 83.3%, and 82.9%, respectively (P=0.001). Conclusion: A high plasma IL-6 level in CHB patients could be an early biomarker for HBV-ACLF.

13.
Front Med (Lausanne) ; 8: 762247, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805229

RESUMO

Immune checkpoint inhibitors (ICIs), which can enhance antitumor immunity and inhibit cancer growth, have revolutionized the treatment of multiple cancers and dramatically decreased mortality. However, treatment with ICIs is directly associated with immune-related adverse events (irAEs) because of inflammation in off-target organs and autoimmunity resulting from non-specific immune activation. These irAEs can cause rheumatic diseases and manifestations such as inflammatory arthritis, polymyalgia rheumatica, myositis, vasculitis, Sicca and Sjogen's syndrome, and systemic lupus erythematosus. Early diagnosis and treatment of these adverse events will improve outcomes and quality of life for cancer patients. The treatment of rheumatic diseases induced by ICIs requires multidisciplinary cooperation among physicians. Furthermore, the underlying mechanisms are not fully understood and it is difficult to predict and evaluate these side effects precisely. In this review, we summarize available studies and findings about rheumatic irAEs, focusing mainly on the clinical manifestations, epidemiology, possible mechanisms, and guiding principles for treating these irAEs.

14.
Opt Express ; 29(23): 38527-38539, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34808904

RESUMO

Laser intensity noise is one of the main limiting factors in pulsed vapor cell clocks. To reduce the contribution of the laser intensity noise to detection signal in the pulsed optically pumped atomic clock, a scheme based on the differential Faraday rotation angle is proposed. Theoretically, the Ramsey fringes, the sensitivity of clock frequency to laser intensity fluctuation and the signal to noise ratio for absorption, differential, and Faraday rotation angle methods are calculated and compared. Using a Wollaston prism rotated 45°relative to the incident polarization, and two photodetectors, Ramsey fringes of three detection methods are obtained simultaneously. In the proposed scheme, the long-term Faraday rotation angle fluctuation is 0.66% at 30000s, which is much smaller than fluctuation of traditional absorption signal 3.9% at 30000s. And the contribution of laser intensity noise to clock instability is also reduced. Using optimized photodetector with high common mode rejection ratio, a better performance should be expected. This proposed scheme is attractive for the development of high performance vapor clock based on pulsed optically pumped.

15.
Front Vet Sci ; 8: 758705, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733908

RESUMO

The Booroola fecundity (Fec B ) gene, as the first major fecundity gene identified in Booroola sheep, has attracted careful attention. So far, previous research have uncovered the FecB mutation (Q249R) as the main mutation by virtue of which sheep exhibits multiple lambing phenomena. This mutation is now being intensively studied and widely used. However, such effect of the FecB mutation has not been applied to goats, and similar types of the Fec B gene in goats still need to be studied. Thus, the current study attempted to verify potential mutations in the goat Fec B gene as well as investigate their functions related to fecundity. First, Fec B expression was investigated in six different goat tissues, and we found that Fec B expression was highest in the mammary gland, followed by the ovary. Next, the influence of the Fec B gene was analyzed from a new perspective, where five potential copy number variations (CNVs) (CNV1-5) within the Fec B gene were identified for the first time, and then their effects on litter size were measured. Our results point out that CNV3 (P = 3.44E-4) and CNV5 (P = 0.034) could significantly influence the litter size of goats. Identically, the combination genotype of CNV3 and CNV5 which consisted of their dominant genotypes was also significantly associated with goat litter size (P = 7.80E-5). Hence, CNV3 and CNV5 could serve as potential DNA molecular markers applied to DNA editing and DNA microarray. Additionally, the abovementioned study has laid a theoretical foundation for the detection of potential fertility-related quantitative trait loci within the goat Fec B gene.

16.
Mol Pharm ; 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34748332

RESUMO

We report the evaluation and prediction of the pharmacokinetic (PK) performance of artemisinin (ART) cocrystal formulations, that is, 1:1 artemisinin/orcinol (ART-ORC) and 2:1 artemisinin/resorcinol (ART2-RES), using in vivo murine animal and physiologically based pharmacokinetic (PBPK) models. The efficacy of the ART cocrystal formulations along with the parent drug ART was tested in mice infected with Plasmodium berghei. When given at the same dose, the ART cocrystal formulation showed a significant reduction in parasitaemia at day 4 after infection compared to ART alone. PK parameters including Cmax (maximum plasma concentration), Tmax (time to Cmax), and AUC (area under the curve) were obtained by determining drug concentrations in the plasma using liquid chromatography-high-resolution mass spectrometry (LC-HRMS), showing enhanced ART levels after dosage with the cocrystal formulations. The dose-response tests revealed that a significantly lower dose of the ART cocrystals in the formulation was required to achieve a similar therapeutic effect as ART alone. A PBPK model was developed using a PBPK mouse simulator to accurately predict the in vivo behavior of the cocrystal formulations by combining in vitro dissolution profiles with the properties of the parent drug ART. The study illustrated that information from classical in vitro and in vivo experimental investigations of the parent drug of ART formulations can be coupled with PBPK modeling to predict the PK parameters of an ART cocrystal formulation in an efficient manner. Therefore, the proposed modeling strategy could be used to establish in vitro and in vivo correlations for different cocrystals intended to improve dissolution properties and to support clinical candidate selection, contributing to the assessment of cocrystal developability and formulation development.

17.
Trends Cancer ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34750090

RESUMO

Plants and associated microorganisms are essential sources of natural products against human cancer diseases, partly exemplified by plant-derived anticancer drugs such as Taxol (paclitaxel). Natural products provide diverse mechanisms of action and can be used directly or as prodrugs for further anticancer optimization. Despite the success, major bottlenecks can delay anticancer lead discovery and implementation. Recent advances in sequencing and omics-related technology have provided a mine of information for developing new therapeutics from natural products. Artificial intelligence (AI), including machine learning (ML), has offered powerful techniques for extensive data analysis and prediction-making in anticancer leads discovery. This review presents an overview of current AI-guided solutions to discover anticancer lead compounds, focusing on natural products from plants and associated microorganisms.

18.
ACS Appl Mater Interfaces ; 13(45): 54516-54526, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34748305

RESUMO

A comparison of hexagonal boron nitride (hBN) layers grown by chemical vapor deposition on C-plane (0001) versus A-plane (112̅0) sapphire (α-Al2O3) substrate is reported. The high deposition temperature (>1200 °C) and hydrogen ambient used for hBN deposition on sapphire substantially alters the C-plane sapphire surface chemistry and leaves the top layer(s) oxygen deficient. The resulting surface morphology due to H2 etching of C-plane sapphire is inhomogeneous with increased surface roughness which causes non-uniform residual stress in the deposited hBN film. In contrast to C-plane, the A-plane of sapphire does not alter substantially under a similar high temperature H2 environment, thus providing a more stable alternative substrate for high quality hBN growth. The E2g Raman mode full width at half-maximum (FWHM) for hBN deposited on C-plane sapphire is 24.5 ± 2.1 cm-1 while for hBN on A-plane sapphire is 24.5 ± 0.7 cm-1. The lesser FWHM standard deviation on A-plane sapphire indicates uniform stress distribution across the film due to reduced undulations on the surface. The photoluminescence spectra of the hBN films at 300 and 3 K, obtained on C-plane and A-plane sapphire exhibit similar characteristics with peaks at 4.1 and 5.3 eV reported to be signature peaks associated with defects for hBN films deposited under lower V/III ratios. The dielectric breakdown field of hBN deposited on A-plane sapphire was measured to be 5 MV cm-1, agreeing well with reports on mechanically exfoliated hBN flakes. Thus, under the typical growth conditions required for high crystalline quality hBN growth, A-plane sapphire provides a more chemically stable substrate.

19.
Sci Rep ; 11(1): 22088, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34764368

RESUMO

The roles of endogenous nitric oxide (NO) derived from the entire NO synthases (NOSs) system have yet to be fully elucidated. We addressed this issue in mice in which all three NOS isoforms were deleted. Under basal conditions, the triple n/i/eNOSs-/- mice displayed significantly longer mean alveolar linear intercept length, increased alveolar destructive index, reduced lung elastic fiber content, lower lung field computed tomographic value, and greater end-expiratory lung volume as compared with wild-type (WT) mice. None of single NOS-/- or double NOSs-/- genotypes showed such features. These findings were observed in the triple n/i/eNOSs-/- mice as early as 4 weeks after birth. Cyclopaedic and quantitative comparisons of mRNA expression levels between the lungs of WT and triple n/i/eNOSs-/- mice by cap analysis of gene expression (CAGE) revealed that mRNA expression levels of three Wnt ligands and ten Wnt/ß-catenin signaling components were significantly reduced in the lungs of triple n/i/eNOSs-/- mice. These results provide the first direct evidence that complete disruption of all three NOS genes results in spontaneous pulmonary emphysema in juvenile mice in vivo possibly through down-regulation of the Wnt/ß-catenin signaling pathway, demonstrating a novel preventive role of the endogenous NO/NOS system in the occurrence of pulmonary emphysema.

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