162 research outputs found

    Improvement of adenoviral vector-mediated gene transfer to airway epithelia by folate-modified anionic liposomes

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    Despite remarkable progress in the development of both viral and nonviral gene delivery vectors for airway disease treatment, poor gene transfer efficiency to the airway epithelium is a major obstacle in clinical application. To take advantage of the unique features of viral and nonviral vectors, we have developed complexes of adenovirus vector and anionic liposomes (AL-Ad5) by the calcium-induced phase change method. In the current study, based on the fact that there are overexpressed folate receptors on the surface of airway epithelia, we further modified the AL-Ad5 complexes with folate (F-AL-Ad5) to improve the transduction ability of Ad5 in airway epithelia. The transduction efficiencies of the obtained F-AL-Ad5 and AL-Ad5 complexes were assessed in primary-cultured airway epithelia in vitro. Our results indicated that compared with naked adenovirus vector, both AL-Ad5 and F-AL-Ad5 could significantly enhance the gene transduction efficiency of adenovirus vector in primary-cultured airway epithelial cells. Moreover, the enhancement mediated by F-AL-Ad5 was more dramatic than that by AL-Ad5. These results suggested that F-AL-Ad5 may be a useful strategy to deliver therapeutic genes to the airway epithelia and is promising in clinical application

    Bethe states of the trigonometric SU(3) spin chain with generic open boundaries

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    By combining the algebraic Bethe ansatz and the off-diagonal Bethe ansatz, we investigate the trigonometric SU(3) model with generic open boundaries. The eigenvalues of the transfer matrix are given in terms of an inhomogeneous T-Q relation, and the corresponding eigenstates are expressed in terms of nested Bethe-type eigenstates which have well-defined homogeneous limit. This exact solution provides a basis for further analyzing the thermodynamic properties and correlation functions of the anisotropic models associated with higher rank algebras.Comment: 17 pages, 3 tables. arXiv admin note: text overlap with arXiv:1705.0947

    Preparation, characterization, and in vivo evaluation of a self-nanoemulsifying drug delivery system (SNEDDS) loaded with morin-phospholipid complex

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    Background: As a poorly water-soluble drug, the oral application of morin is limited by its low oral bioavailability. In this study, a new self-nanoemulsifying drug delivery system (SNEDDS), based on the phospholipid complex technique, was developed to improve the oral bioavailability of morin. Methods: Morin-phospholipid complex (MPC) was prepared by a solvent evaporation method and characterized by infrared spectroscopy and X-ray diffraction. After formation of MPC, it was found that the liposolubility of morin was significantly increased, as verified through solubility studies. An orthogonal design was employed to screen the blank SNEDDS, using emulsifying rate and particle size as evaluation indices. Ternary phase diagrams were then constructed to investigate the effects of drug loading on the self-emulsifying performance of the optimized blank SNEDDS. Subsequently, in vivo pharmacokinetic parameters of the morin-phospholipid complex self-nanoemulsifying drug delivery system (MPC-SNEDDS) were investigated in Wistar rats (200 mg/kg of morin by oral administration). Results: The optimum formulation was composed of Labrafil (R) M 1944 CS, Cremophor (R) RH 40, and Transcutol (R) P (3: 5: 3, w/w), which gave a mean particle size of approximately 140 nm. Oral delivery of the MPC-SNEDDS exhibited a significantly greater C(max) (28.60 mu g/mL) than the morin suspension (5.53 mu g/mL) or MPC suspension (23.74 mu g/mL) (all P < 0.05). T(max) was prolonged from 0.48 to 0.77 hours and to 1 hour for MPC and MPC-SNEDDS, respectively. In addition, the relative oral bioavailability of morin formulated in the MPC-SNEDDS was 6.23-fold higher than that of the morin suspension, and was significantly higher than that of the MPC suspension (P < 0.05). Conclusion: The study demonstrated that a SNEDDS combined with the phospholipid complex technique was a promising strategy to enhance the oral bioavailability of morin.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000298166900001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Nanoscience & NanotechnologyPharmacology & PharmacySCI(E)24ARTICLE3405-3414

    Thermodynamic limit and twisted boundary energy of the XXZ spin chain with antiperiodic boundary condition

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    We investigate the thermodynamic limit of the inhomogeneous T-Q relation of the antiferromagnetic XXZ spin chain with antiperiodic boundary condition. It is shown that the contribution of the inhomogeneous term at the ground state can be neglected when the system-size N tends to infinity, which enables us to reduce the inhomogeneous Bethe ansatz equations (BAEs) to the homogeneous ones. Then the quantum numbers at the ground states are obtained, by which the system with arbitrary size can be studied. We also calculate the twisted boundary energy of the system.Comment: 18 pages, 7 figure

    A single-cell analysis of the molecular lineage of chordate embryogenesis

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    Progressive unfolding of gene expression cascades underlies diverse embryonic lineage development. Here, we report a single-cell RNA sequencing analysis of the complete and invariant embryonic cell lineage of the tunicate Ciona savignyi from fertilization to the onset of gastrulation. We reconstructed a developmental landscape of 47 cell types over eight cell cycles in the wild-type embryo and identified eight fate transformations upon fibroblast growth factor (FGF) inhibition. For most FGF-dependent asymmetric cell divisions, the bipotent mother cell displays the gene signature of the default daughter fate. In convergent differentiation of the two notochord lineages, we identified additional gene pathways parallel to the master regulator T/Brachyury. Last, we showed that the defined Ciona cell types can be matched to E6.5-E8.5 stage mouse cell types and display conserved expression of limited number of transcription factors. This study provides a high-resolution single-cell dataset to understand chordate early embryogenesis and cell lineage differentiation

    Mixed methods to explore factors associated with the decline of patients in the methadone maintenance treatment program in Shanghai, China

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    BACKGROUND: This study was to characterize the Methadone Maintenance Treatment (MMT) in Shanghai, China, and to explore factors associated with the decline of patients in MMT during 2005-2016. METHODS: Both qualitative and quantitative methods were used in this study. Based on the data from Shanghai Centers for Disease Control (CDC), we described the changes in the number of patients who received MMT, and new enrollment each year from 2005 to 2016. Focus groups were conducted with 22 patients, and in-depth interviews were conducted with 9 service providers. RESULTS: Quantitative data demonstrate that the number of new enrollment began to decline in 2009, and the number of patients receiving MMT began to decline in 2012. The main reasons for dropout include (1) discontinuing medication due to unknown reasons (25%), (2) criminal activities other than drug-related crimes (20%), (3) relapse to heroin use (16%), and (4) physical disease (10%). Qualitative assessment results indicate that the major reasons for the decline of patients in MMT are as follows: (1) the increase of Amphetamine-type stimulants (ATS) use in recent years, (2) limited knowledge about MMT in both patients and MMT staff, (3) complicated enrollment criteria, and (4) discrimination against drug use. CONCLUSION: Various reasons to explain the decline of patients in MMT in Shanghai, China, were identified. Government agencies, service providers, and other stakeholders need to work together and overcome identified barriers to support MMT programs in China

    Impact of GLP-1 Receptor Agonists on Major Gastrointestinal Disorders for Type 2 Diabetes Mellitus: A Mixed Treatment Comparison Meta-Analysis

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    Aim. We aimed to integrate evidence from all randomized controlled trials (RCTs) and assess the impact of different doses of exenatide or liraglutide on major gastrointestinal adverse events (GIAEs) in type 2 diabetes (T2DM). Methods. RCTs evaluating different doses of exenatide and liraglutide against placebo or an active comparator with treatment duration ≥4 weeks were searched and reviewed. A total of 35, 32 and 28 RCTs met the selection criteria evaluated for nausea, vomiting, and diarrhea, respectively. Pairwise random-effects meta-analyses and mixed treatment comparisons (MTC) of all RCTs were performed. Results. All GLP-1 dose groups significantly increased the probability of nausea, vomiting and diarrhea relative to placebo and conventional treatment. MTC meta-analysis showed that there was 99.2% and 85.0% probability, respectively, that people with exenatide 10 μg twice daily (EX10BID) was more vulnerable to nausea and vomiting than those with other treatments. There was a 78.90% probability that liraglutide 1.2 mg once daily (LIR1.2) has a higher risk of diarrhea than other groups. A dose-dependent relationship of exenatide and liraglutide on GIAEs was observed. Conclusions. Our MTC meta-analysis suggests that patients should be warned about these GIAEs in early stage of treatment by GLP-1s, especially by EX10BID and LIR1.2, to promote treatment compliance

    Global, Regional, and National Change Patterns in the Incidence of Low Back Pain From 1990 to 2019 and Its Predicted Level in the Next Decade

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    Objectives: To analyze and describe the spatiotemporal trends of Low back pain (LBP) burdens from 1990 to 2019 and anticipate the following decade’s incidence.Methods: Using data from the Global Burden of Disease (GBD) 2019 Study, we described net drifts, local drifts, age effects, and period cohort effects in incidence and forecasted incidence rates and cases by sex from 2020 to 2029 using the Nordpred R package.Results: LBP remained the leading cause of the musculoskeletal disease burden globally and across all socio-demographic index (SDI) regions. China is the top country. For recent periods, high-SDI countries faced unfavorable or worsening risks. The relative risk of incidence showed improving trends over time and in successively younger birth cohorts amongst low-middle-, middle- and high-middle-SDI countries. Additionally, the age-standardized incidence rates (ASIR) of LBP in both sexes globally showed a decreasing trend, but the incident cases would increase from 223 to 253 million overall in the next decade.Conclusion: As the population ages, incident cases will rise but ASIR will fall. To minimise LBP, public awareness and disease prevention and control are needed

    Forced Notch Signaling Inhibits Commissural Axon Outgrowth in the Developing Chick Central Nerve System

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    BACKGROUND: A collection of in vitro evidence has demonstrated that Notch signaling plays a key role in the growth of neurites in differentiated neurons. However, the effects of Notch signaling on axon outgrowth in an in vivo condition remain largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study, the neural tubes of HH10-11 chick embryos were in ovo electroporated with various Notch transgenes of activating or inhibiting Notch signaling, and then their effects on commissural axon outgrowth across the floor plate midline in the chick developing central nerve system were investigated. Our results showed that forced expression of Notch intracellular domain, constitutively active form of RBPJ, or full-length Hes1 in the rostral hindbrain, diencephalon and spinal cord at stage HH10-11 significantly inhibited commissural axon outgrowth. On the other hand, inhibition of Notch signaling by ectopically expressing a dominant-negative form of RBPJ promoted commissural axonal growth along the circumferential axis. Further results revealed that these Notch signaling-mediated axon outgrowth defects may be not due to the alteration of axon guidance since commissural axon marker TAG1 was present in the axons in floor plate midline, and also not result from the changes in cell fate determination of commissural neurons since the expression of postmitotic neuron marker Tuj1 and specific commissural markers TAG1 and Pax7 was unchanged. CONCLUSIONS/SIGNIFICANCE: We first used an in vivo system to provide evidence that forced Notch signaling negatively regulates commissural axon outgrowth
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