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Mikael Lindahl, Jeanette Hellgren Kotaleski
The basal ganglia are a crucial brain system for behavioral selection, and their function is disturbed in Parkinson's disease (PD), where neurons exhibit inappropriate synchronization and oscillations. We present a spiking neural model of basal ganglia including plausible details on synaptic dynamics, connectivity patterns, neuron behavior, and dopamine effects. Recordings of neuronal activity in the subthalamic nucleus and Type A (TA; arkypallidal) and Type I (TI; prototypical) neurons in globus pallidus externa were used to validate the model...
November 2016: ENeuro
Xiaolu Chen, Hui Sun, Jun Hu, Xia Han, Honglai Liu, Ying Hu
This work reports on a targeted and controlled drug delivery system based on protein decorated mesoporous silica nanoparticles (MSNs). In this system, transferrin (Tf), a naturally existing protein, is grafted on the surfaces of MSNs via redox-cleavable disulfide bonds, serving as both a capping agent and a targeting ligand simultaneously. The uniform particles with ordered mesoporous structures and the successful construction of the Tf/MSN hybrid nanocarriers can be confirmed through combined techniques. It is found that the model anticancer drug doxorubicin (DOX) can be efficiently encapsulated in the MSNs in the absence of glutathione (GSH), and a burst release of DOX is observed when the system is exposed to GSH, indicating good capping efficiency of Tf and redox-responsive release of DOX...
January 8, 2017: Colloids and Surfaces. B, Biointerfaces
Fen Wei, Qi Hu, Jing Huang, Shengli Han, Sicen Wang
Corydalis Thizoma,or Yuanhu in China, is a common herbal drug used for thousands of years as analgesic in Chinese medicine that has been reported to have potential anti-angiogenic effects. In this study, a VEGFR/cell membrane chromatography (VEGFR/CMC) coupled with HPLC- ESI-IT-TOF-MSn system was developed and successfully applied for identifying active components from YuanHu extract acting on VEGFR. We identified tetrahydropalmatine and corydaline as bioactive components with VEGFR activity, thus confirming their inhibitory activity on VEGFR engineered HEK293 cell growth by MTT assay...
January 4, 2017: Journal of Pharmaceutical and Biomedical Analysis
Shuwen Peng, Yuanyuan He, Murat Er, Yuanzhi Sheng, Yueqing Gu, Haiyan Chen
Near-infrared (NIR) photothermal therapy (PTT) is a new approach to ablate cancer without affecting normal tissues. A pivotal concern of PPT is to develop photo-responsive agents with high biocompatibility as well as effective photothermal conversion efficiency. Copper sulfide (CuS) nanoparticles prepared are characterized by their low synthesis cost, wide NIR absorption range, good biocompatibility and favorable NIR photothermal conversion efficiency. CuS nanoparticles were then coated with mesoporous silicon dioxide (SiO2) by the Stober method, and further loaded with anticancer drug doxorubicin (DOX)...
January 12, 2017: Biomaterials Science
Hugo A Tejeda, Jocelyn Wu, Alana R Kornspun, Marco Pignatelli, Vadim Kashtelyan, Michael J Krashes, Brad B Lowell, William A Carlezon, Antonello Bonci
Endogenous dynorphin signaling via the kappa-opioid receptor (KOR) in the nucleus accumbens (NAcc) powerfully mediates negative affective states and stress reactivity. Excitatory inputs from the hippocampus and amygdala play a fundamental role in shaping the activity of both NAcc D1 and D2 MSNs, which encode positive and negative motivational valences, respectively. However, a circuit-based mechanism by which KOR modulation of excitation-inhibition balance modifies D1 and D2 MSN activity is lacking. Here, we provide a comprehensive synaptic framework wherein presynaptic KOR inhibition decreases the excitatory drive of D1 MSN activity by the amygdala, but not the hippocampus...
January 4, 2017: Neuron
Akinori Nishi, Takahide Shuto
Alterations in dopamine neurotransmission has been implicated in pathophysiology of neuropsychiatric and neurodegenerative disorders, and DARPP-32 plays a pivotal role in dopamine neurotransmission. DARPP-32 likely influences dopamine-mediated behaviors in animal models of neuropsychiatric and neurodegenerative disorders and therapeutic effects of pharmacological treatment. Areas covered: We will review animal studies on the biochemical and behavioral roles of DARPP-32 in drug addiction, schizophrenia and Parkinson's disease...
January 13, 2017: Expert Opinion on Therapeutic Targets
Mahmonir Karimzadeh, Ladan Rashidi, Fariba Ganji
Rivastigmine hydrogen tartrate (RT) is a molecule with both hydrophilic and hydrophobic properties used for the treatment of the Alzheimer's disease. In this work, the larger pore size of mesoporous silica nanoparticles (P1-MSN) was synthesized and then, P1-MSN were functionalized by succinic anhydride (S-P1-MSN) and 3-aminopropyltriethoxysilane (APTES) (AP-CO-P1-MSN) using the grafting and co-condensation methods, respectively. A new method was used for the functionalization of P1-MSN by succinic anhydride at room temperature...
January 3, 2017: Drug Development and Industrial Pharmacy
Manuela Rizzi, Stelvio Tonello, Bianca Martins Estevão, Enrica Gianotti, Leonardo Marchese, Filippo Renò
Photodinamic therapy (PDT) has gained an increasing interest as a new tool to treat skin cancers such as melanoma. This clinical approach take advantage from the combination of a photosensitizer and a specific light wavelength able to induce singlet oxygen production. Mesoporous silica nanoparticles (MSNs) have been widely investigated as drug nanocarriers as their structure and morphology could be customized to produce suitable nanoplatforms enabling high cargo capacity. In the present study MSNs were successfully conjugated with the second generation photosensitizer verteporfin and the resulting nanoplatform (Ver-MSNs) was tested in an in vitro PDT model as a potential tool for melanoma treatment...
December 22, 2016: Journal of Photochemistry and Photobiology. B, Biology
Yin-Jia Cheng, Ai-Qing Zhang, Jing-Jing Hu, Feng He, Xuan Zeng, Xian-Zheng Zhang
A tumor targeting redox-responsive drug delivery system (DDS) with bioactive surface was constructed by immobilizing peptide-based amphiphile C12-CGRKKRRQRRRPPQRGDS (defined as ADDA-TCPP) onto the mesoporous silica nanoparticles (MSNs) as an end-capping nanovalve, which consists of two main segments: a hydrophobic alkyl chain ADDA and a hydrophilic amino acid sequence containing a Tat48-60 peptide sequence with a thiol terminal group and an RGDS targeting ligand, via a disulfide linkage for redox-triggered intracellular drug delivery...
January 12, 2017: ACS Applied Materials & Interfaces
Gloria Berlier, Geo Paul, Giorgia Elena Musso, Emanuela Bottinelli, Maurizio Cossi, Leonardo Marchese
The interaction of water molecules with the surface of hybrid silica based mesoporous materials is studied by 29Si, 1H, 13C Solid State Nuclear Magnetic Resonance (SS NMR) and infrared spectroscopy, and supported by ab initio calculations. The surface of aminopropyl grafted mesoporous silica nanoparticles (NH2-MSN) was studied in the dehydrated state and upon interaction with controlled doses of water vapour. Former investigations described the interactions between aminopropyl and residual Si-OH groups: the present study shows the presence of hydrogen bonded species (Si-OH to NH2) and weakly interacting "free" aminopropyl chains with a restricted mobility, together with a small amount of protonated NH3+ groups...
December 28, 2016: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
Nhat Tri Vo, Astam K Patra, Dukjoon Kim
Mesoporous silica nanoparticles (MSNs) with uniform size (<50 nm) yet with different pore diameters were synthesized, and used as fillers in poly(ether sulfone) (PES) films in order to decrease their coefficient of thermal expansion (CTE) without sacrificing optical transparency. Here, both CTE and optical transparency of the MSN/PES nanocomposite films gradually decreased with increasing MSN concentration. The PES films containing MSNs with larger pores showed the best performance in CTE and optical transparency...
January 18, 2017: Physical Chemistry Chemical Physics: PCCP
Gloria Zaccariello, Michele Back, Marta Zanello, Patrizia Canton, Elti Cattaruzza, Pietro Riello, Alessandro Alimonti, Alvise Benedetti
The application of nanosized inorganic UV filters in cosmetic field is limited by their high photocatalytic properties that could induce the degradation or dangerous transformation of the organic molecules in sunscreen formulations. To overcome this problem and simultaneously enlarge the window of filter's absorption, we propose the growth of bismuth titanates BixTiyOz into mesoporous silica nanoparticles (MSN). We investigated the chemical-physical properties by means of XRPD, TEM, UV-vis spectroscopy, N2 physisorption, XPS, and SF-ICP-MS analysis, while the influence on the environment was evaluated through photocatalytic tests...
January 18, 2017: ACS Applied Materials & Interfaces
Neeraj Prabhakar, Jixi Zhang, Diti Desai, Eudald Casals, Tina Gulin-Sarfraz, Tuomas Näreoja, Jukka Westermarck, Jessica M Rosenholm
Small interfering RNA (siRNA) is a highly potent drug in gene-based therapy with the challenge being to deliver it in a sustained manner. The combination of mesoporous silica nanoparticles (MSNs) and polycations in the confined pore space allows for incorporation and controlled release of therapeutic siRNA payloads. We hereby constructed MSNs with expanded mesopores and pore-surface-hyperbranched poly(ethyleneimine) (PEI) tethered with redox-cleavable linkers that could carry a high payload of siRNA (120 mg·g(-1))...
2016: International Journal of Nanomedicine
Nikhil Biswas
The aim was to improve the oral bioavailability and antihypertensive activity of poorly soluble drug valsartan (VAL) by modifying the design and delivery of mesoporous silica nanoparticles (MSNs). The synthesized MSNs were functionalized with aminopropyl groups (AP-MSN) through postsynthesis and coated with pH sensitive polymer Eudragit L100-55 (AP-MSN-L100-55) for pH dependant sustain release of anionic VAL. MSNs were characterized by Brauner-Emmett-Teller (BET) surface area analyzer, zeta sizer, Field Emission Scanning Electron Microscope (FESEM), Powder X-Ray Diffraction (PXRD) and Differential Scanning Calorimetry (DSC)...
December 18, 2016: European Journal of Pharmaceutical Sciences
Yao Shen, Jinjun Hou, Wen Deng, Zijin Feng, Min Yang, Jinle Cheng, Wanying Wu, De-An Guo
Salvia miltiorrhiza is one of the most used herbal medicines for the treatment of a wide range of diseases in China. Decoction pieces and Chinese patent medicines from S. miltiorrhiza are the two main types of products used by patients. Other relatively new products of S. miltiorrhiza, like injections and ultrafine granular powder (D90 < 45 µm before granulation), are also increasingly used nowadays. With the growing usage of new products of S. miltiorrhiza, their chemical components and pharmacological effects, compared to the traditional decoction pieces, are attracting attention...
December 19, 2016: Planta Medica
Gauri V Deodhar, Marisa L Adams, Brian G Trewyn
Protein therapeutics are promising candidates for disease treatment due to their high specificity and minimal adverse side effects; however, targeted protein delivery to specific sites has proven challenging. Mesoporous silica nanoparticles (MSN) have demonstrated to be ideal candidates for this application, given their high loading capacity, biocompatibility, and ability to protect host molecules from degradation. These materials exhibit tunable pore sizes, shapes and volumes, and surfaces which can be easily functionalized...
December 14, 2016: Biotechnology Journal
Liang Chen, Xiaojun Zhou, Wei Nie, Qianqian Zhang, Weizhong Wang, Yanzhong Zhang, Chuanglong He
The convenient modification of mesoporous silica nanoparticles (MSN) can provide great opportunities for constructing a new generation of nanocarriers with multiple functions. In the current study, we fabricated a new multifunctional drug delivery system based on MSN capped by gadolinium-based bovine serum albumin complex (BSA-Gd) and hyaluronic acid (HA) via reductive-cleavable disulfide bond. In this multifunctional nanoparticle (MSN-ss-GHA), BSA-Gd component was prepared by biomineralization and acted as both smart gatekeeper and contrast agent for magnetic resonance (MR) imaging, while HA served as the targeted molecule to improve the specific affinity of MSN-ss-GHA toward cancer cells...
December 14, 2016: ACS Applied Materials & Interfaces
Jia Wen, Kui Yang, Yongqian Xu, Hongjuan Li, Fengyu Liu, Shiguo Sun
In this work, a triple-stimuli (GSH, pH and light irradiation) responsive system were designed based on CeO2 nanoparticles (CeO2 NPs) coated doxorubicin (DOX) and photosensitizer hematoporphyrin (HP) dual-loaded mesoporous silica nanoparticles (MSN). Upon entering into cancer cells, both high concentration of intracellular GSH and low pH environment would reduce CeO2 NPs to cerium ions, accompanied with the degradation of CeO2 NPs and the conformational change of HP under light irradiation, the preloaded DOX are thus released from the nanocarrier, resulting in a contrast fluorescence enhancement...
December 12, 2016: Scientific Reports
Ramesh Chandra, Michel Engeln, T Chase Francis, Prasad Konkalmatt, Dipal Patel, Mary Kay Lobo
BACKGROUND: Molecules critically involved in cocaine behavioral plasticity are known to regulate and interact with peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α). In addition, the PGC-1α promoter has binding sites for early growth response 3 (Egr3), which plays a dynamic role in cocaine action in nucleus accumbens (NAc) medium spiny neuron (MSN) subtypes, those enriched in dopamine receptor D1 (D1-MSN) versus D2 (D2-MSN). However, the role of PGC-1α in NAc in cocaine action is unknown...
October 28, 2016: Biological Psychiatry
Jing Tu, Aimee L Boyle, Heiner Friedrich, Paul H H Bomans, Jeroen Bussmann, Nico A J M Sommerdijk, Wim Jiskoot, Alexander Kros
Mesoporous silica nanoparticles (MSNs) have been explored extensively as solid supports for proteins in biological and medical applications. Small (<200 nm) MSNs with ordered large pores (>5 nm), capable of encapsulating therapeutic small molecules suitable for delivery applications in vivo, are rare however. Here we present small, elongated, cuboidal, MSNs with average dimensions of 90 × 43 nm that possess disk-shaped cavities, stacked on top of each other, which run parallel to the short axis of the particle...
November 30, 2016: ACS Applied Materials & Interfaces
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