The Experts below are selected from a list of 522 Experts worldwide ranked by ideXlab platform

Nan Wang - One of the best experts on this subject based on the ideXlab platform.

  • construction of biomimetic long circulation delivery platform encapsulated by zwitterionic polymers for enhanced penetration of blood brain barrier
    RSC Advances, 2017
    Co-Authors: Nan Wang
    Abstract:

    The effective treatments for central nervous system (CNS) diseases are impeded mostly by the existence of the blood–brain barrier (BBB). The accumulation of therapeutic drugs inside the brain is far from the therapy threshold, which is closely related to the transient circulation time of drugs and their carriers. Herein, a core–shell protein-based long-circulation delivery platform was constructed. Through in situ free radical polymerization, a zwitterionic polymer poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) was modified on the surface to prolong the circulation lifetime with a biomimetic structure induced by a phosphorylcholine (PC) head-group similar to the lipids in the outer membrane of living cells. A cell-penetrating peptide, HIV-1 trans-activating Transcriptor (TAT) was conjugated on the surface of the protein-based nanoparticles, endowing the delivery platform with BBB-crossing ability. The BBB-permeability of the nanoparticles was investigated both in vitro and in vivo. Encapsulated with zwitterionic polymer PMPC, the nanoparticles showed a long circulation lifetime due to strong resistance to nonspecific adsorption and provided a better chance for BBB penetration. The delivery platform had enhanced permeability for BBB and a longer retention time inside the brain in a healthy mouse model. Overall, the surface modification with zwitterionic polymer PMPC and cell-penetrating peptide TAT changes the circulation modality of the nanoparticles in vivo, and provides a promising pathway for BBB crossing as a potential drug delivery platform for CNS related disease therapy.

  • iron chelation nanoparticles with delayed saturation as an effective therapy for parkinson disease
    Biomacromolecules, 2017
    Co-Authors: Nan Wang, Xin Jin, Dongbo Guo, Gangsheng Tong, Xinyuan Zhu
    Abstract:

    Iron accumulation in substantia nigra pars compacta (SNpc) has been proved to be a prominent pathophysiological feature of Parkinson’s diseases (PD), which can induce the death of dopaminergic (DA) neurons, up-regulation of reactive oxygen species (ROS), and further loss of motor control. In recent years, iron chelation therapy has been demonstrated to be an effective treatment for PD, which has shown significant improvements in clinical trials. However, the current iron chelators are suboptimal due to their short circulation time, side effects, and lack of proper protection from chelation with ions in blood circulation. In this work, we designed and constructed iron chelation therapeutic nanoparticles protected by a zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) to delay the saturation of iron chelators in blood circulation and prolong the in vivo lifetime, with HIV-1 trans-activating Transcriptor (TAT) served as a shuttle to enhance the blood-brain barrier (BBB) permeability. We expl...

  • Iron Chelation Nanoparticles with Delayed Saturation as an Effective Therapy for Parkinson Disease
    2016
    Co-Authors: Nan Wang, Xin Jin, Dongbo Guo, Gangsheng Tong, Xinyuan Zhu
    Abstract:

    Iron accumulation in substantia nigra pars compacta (SNpc) has been proved to be a prominent pathophysiological feature of Parkinson’s diseases (PD), which can induce the death of dopaminergic (DA) neurons, up-regulation of reactive oxygen species (ROS), and further loss of motor control. In recent years, iron chelation therapy has been demonstrated to be an effective treatment for PD, which has shown significant improvements in clinical trials. However, the current iron chelators are suboptimal due to their short circulation time, side effects, and lack of proper protection from chelation with ions in blood circulation. In this work, we designed and constructed iron chelation therapeutic nanoparticles protected by a zwitterionic poly­(2-methacryloyloxyethyl phosphorylcholine) (PMPC) to delay the saturation of iron chelators in blood circulation and prolong the in vivo lifetime, with HIV-1 trans-activating Transcriptor (TAT) served as a shuttle to enhance the blood-brain barrier (BBB) permeability. We explored and investigated whether the Parkinsonian neurodegeneration and the corresponding symptoms in behaviors and physiologies could be prevented or reversed both in vitro and in vivo. The results demonstrated that iron chelator loaded therapeutic nanoparticles could reverse functional deficits in Parkinsonian mice not only physiologically but also behaviorally. On the contrary, both untreated PD mice and non-TAT anchored nanoparticle treated PD mice showed similar loss in DA neurons and difficulties in behaviors. Therefore, with protection of zwitterionic polymer and prolonged in vivo lifetime, iron chelator loaded nanoparticles with delayed saturation provide a PD phenotype reversion therapy and significantly improve the living quality of the Parkinsonian mice

Vinod Labhasetwar - One of the best experts on this subject based on the ideXlab platform.

  • tat conjugated nanoparticles for the cns delivery of anti hiv drugs
    Biomaterials, 2008
    Co-Authors: Kavitha S Rao, Maram K Reddy, Jayme L Horning, Vinod Labhasetwar
    Abstract:

    We have shown that nanoparticles (NPs) conjugated to trans-activating Transcriptor (TAT) peptide bypass the efflux action of P-glycoprotein and increase the transport of the encapsulated ritonavir, a protease inhibitor (PI), across the blood-brain-barrier (BBB) to the central nervous system (CNS). A steady increase in the drug parenchyma/capillary ratio over time without disrupting the BBB integrity suggests that TAT-conjugated NPs are first immobilized in the brain vasculature prior to their transport into parenchyma. Localization of NPs in the brain parenchyma was further confirmed with histological analysis of the brain sections. The brain drug level with conjugated NPs was 800-fold higher than that with drug in solution at two weeks. Drug clearance was seen within four weeks. In conclusion, TAT-conjugated NPs enhanced the CNS bioavailability of the encapsulated PI and maintained therapeutic drug levels in the brain for a sustained period that could be effective in reducing the viral load in the CNS, which acts as a reservoir for the replicating HIV-1 virus.

Xinyuan Zhu - One of the best experts on this subject based on the ideXlab platform.

  • iron chelation nanoparticles with delayed saturation as an effective therapy for parkinson disease
    Biomacromolecules, 2017
    Co-Authors: Nan Wang, Xin Jin, Dongbo Guo, Gangsheng Tong, Xinyuan Zhu
    Abstract:

    Iron accumulation in substantia nigra pars compacta (SNpc) has been proved to be a prominent pathophysiological feature of Parkinson’s diseases (PD), which can induce the death of dopaminergic (DA) neurons, up-regulation of reactive oxygen species (ROS), and further loss of motor control. In recent years, iron chelation therapy has been demonstrated to be an effective treatment for PD, which has shown significant improvements in clinical trials. However, the current iron chelators are suboptimal due to their short circulation time, side effects, and lack of proper protection from chelation with ions in blood circulation. In this work, we designed and constructed iron chelation therapeutic nanoparticles protected by a zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) to delay the saturation of iron chelators in blood circulation and prolong the in vivo lifetime, with HIV-1 trans-activating Transcriptor (TAT) served as a shuttle to enhance the blood-brain barrier (BBB) permeability. We expl...

  • Iron Chelation Nanoparticles with Delayed Saturation as an Effective Therapy for Parkinson Disease
    2016
    Co-Authors: Nan Wang, Xin Jin, Dongbo Guo, Gangsheng Tong, Xinyuan Zhu
    Abstract:

    Iron accumulation in substantia nigra pars compacta (SNpc) has been proved to be a prominent pathophysiological feature of Parkinson’s diseases (PD), which can induce the death of dopaminergic (DA) neurons, up-regulation of reactive oxygen species (ROS), and further loss of motor control. In recent years, iron chelation therapy has been demonstrated to be an effective treatment for PD, which has shown significant improvements in clinical trials. However, the current iron chelators are suboptimal due to their short circulation time, side effects, and lack of proper protection from chelation with ions in blood circulation. In this work, we designed and constructed iron chelation therapeutic nanoparticles protected by a zwitterionic poly­(2-methacryloyloxyethyl phosphorylcholine) (PMPC) to delay the saturation of iron chelators in blood circulation and prolong the in vivo lifetime, with HIV-1 trans-activating Transcriptor (TAT) served as a shuttle to enhance the blood-brain barrier (BBB) permeability. We explored and investigated whether the Parkinsonian neurodegeneration and the corresponding symptoms in behaviors and physiologies could be prevented or reversed both in vitro and in vivo. The results demonstrated that iron chelator loaded therapeutic nanoparticles could reverse functional deficits in Parkinsonian mice not only physiologically but also behaviorally. On the contrary, both untreated PD mice and non-TAT anchored nanoparticle treated PD mice showed similar loss in DA neurons and difficulties in behaviors. Therefore, with protection of zwitterionic polymer and prolonged in vivo lifetime, iron chelator loaded nanoparticles with delayed saturation provide a PD phenotype reversion therapy and significantly improve the living quality of the Parkinsonian mice

Alain Woda - One of the best experts on this subject based on the ideXlab platform.

  • Effects of increased hardness on jaw movement and muscle activity during chewing of visco-elastic model foods
    Experimental Brain Research, 2002
    Co-Authors: Marie-agnès Peyron, C. Lassauzay, Alain Woda
    Abstract:

    When food is chewed, sensory feedback adapts the motor program to the characteristics of the food. However, the relationship between the physical properties of different foods and the motor response is poorly understood. In this study, we developed edible and well-controlled model foods in order to describe some of the stimulus-response functions of the food-mastication loop. Four gelatine-based visco-elastic model foods identical in shape and size but differing in hardness were prepared. They displayed reproducible sensory and physical characteristics and were distributed on a wide hardness scale. Electromyographic activity of masseter and temporalis muscles and jaw movements in the frontal plane were simultaneously recorded during mastication in 15 young men with intact dentition and good oral status. Almost all EMG and jaw movement parameters were clearly affected by increasing hardness of model foods. However, it is possible to summarise the results by reducing the number of parameters to three: the number of chewing cycles, EMG activity of any one of the two temporal or the two masseter muscles and the amplitude of the opening mandibular movements. Indeed, these were the best Transcriptors of the hardness range of the model foods used in this study. As inferred from these parameter recordings, the food hardness modifications were strongest during the first five strokes, began as early as the first stroke and lasted for the whole sequence.

Outi Makitie - One of the best experts on this subject based on the ideXlab platform.

  • a novel myt1l mutation in a patient with severe early onset obesity and intellectual disability
    American Journal of Medical Genetics Part A, 2018
    Co-Authors: Petra Loid, Riikka E Makitie, Alice Costantini, Heli Viljakainen, Minna Pekkinen, Outi Makitie
    Abstract:

    The genetic background of severe early-onset obesity is still incompletely understood. Deletions at 2p25.3 associate with early-onset obesity and variable intellectual disability. Myelin-Transcriptor-factor-1-like (MYT1L) gene in this locus has been proposed a candidate gene for obesity. We report on a 13-year-old boy presenting with overweight already at 1 year of age (body mass index [BMI] Z-score +2.3) and obesity at 2 years of age (BMI Z-score +3.8). The patient had hyperphagia and delayed neurological, cognitive and motor development. He also had speech delay, strabismus, hyperactivity and intellectual disability. Brain MRI was normal. The parents and sister had normal BMI. Whole-genome sequencing identified in the index patient a novel de novo frameshift deletion that introduces a premature termination of translation NM_015025.2(MYT1L): c.2215_2224delACGCGCTGCC, p.(Thr739Alafs*7) in MYT1L. The frameshift variant was confirmed by Sanger sequencing. Our finding supports the association of MYT1L mutations with early-onset syndromic obesity. The identification of novel monogenic forms of childhood-onset obesity will provide insights to the involved genetic and biologic pathways.