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91.
Bajestan SN Umehara F Shirahama Y Itoh K Sharghi-Namini S Jessen KR Mirsky R Osame M 《Journal of neurobiology》2006,66(3):243-255
Hedgehog proteins are important in the development of the nervous system. As Desert hedgehog (Dhh) is involved in the development of peripheral nerves and is expressed in adult nerves, it may play a role in the maintenance of adult nerves and degeneration and regeneration after injury. We firstly investigated the Dhh-receptors, which are expressed in mouse adult nerves. The Dhh receptor patched(ptc)2 was detected in adult sciatic nerves using RT-PCR, however, ptc1 was undetectable under the same experimental condition. Using RT-PCR in purified cultures of mouse Schwann cells and fibroblasts, we found ptc2 mRNA in Schwann cells, and at much lower levels, in fibroblasts. By immunohistochemistry, Ptc2 protein was seen on unmyelinated nerve fibers. Then we induced crush injury to the sciatic nerves of wild-type (WT) and dhh-null mice and the distal stumps of injured nerves were analyzed morphologically at different time points and expression of dhh and related receptors was also measured by RT-PCR in WT mice. In dhh-null mice, degeneration of myelinated fibers was more severe than in WT mice. Furthermore, in regenerated nerves of dhh-null mice, minifascicular formation was even more extensive than in dhh-null intact nerves. Both dhh and ptc2 mRNA levels were down-regulated during the degenerative phase postinjury in WT mice, while levels rose again during the phase of nerve regeneration. These results suggest that the Dhh-Ptc2 signaling pathway may be involved in the maintenance of adult nerves and may be one of the factors that directly or indirectly determines the response of peripheral nerves to injury. 相似文献
92.
Kai Schiemann Dirk Finsinger Frank Zenke Christiane Amendt Thorsten Knöchel David Bruge Hans-Peter Buchstaller Ulrich Emde Wolfgang Stähle Soheila Anzali 《Bioorganic & medicinal chemistry letters》2010,20(5):1491-1495
Here we describe the discovery and optimization of hexahydro-2H-pyrano[3,2-c]quinolines (HHPQs) as potent and selective inhibitors of the mitotic kinesin-5 originally found during a high-throughput screening (HTS) campaign sampling our in-house compound collection. The compounds optimized subsequently and characterized herein were potently inhibiting the ATPase activity of Kinesin-5 and also exhibited consistent cellular activity, in that cells arrested in mitosis and apoptosis induction could be observed. X-ray crystallographic data demonstrated that these inhibitors bind in an allosteric pocket of Kinesin-5 distant from the nucleotide and microtubule binding sites. The selected clinical candidate EMD 534085 caused strong growth inhibition in human tumor xenograft models using Colo 205 colon carcinoma cells at doses below 30 mg/kg administered twice weekly without showing severe toxicity as determined by loss of body weight. 相似文献
93.
Mehnoosh Ashja-Arvan Moein Dehbashi Asma Eslami Hossein Salehi Mahdiyeh Yoosefi Mazdak Ganjalikhani-Hakemi 《Journal of cellular physiology》2020,235(11):8736-8746
Adipose-derived stem cells (ADSCs) are a subset of mesenchymal stem cells that their therapeutic effects in various diseases make them an interesting tool in cell therapy. In the current study, we aimed to overexpress interferon-β (IFN-β) and leukemia inhibitory factor (LIF) cytokines in human ADSCs to evaluate the impact of this overexpression on human ADSCs properties. Here, we designed a construct containing IFN-β and LIF and then, transduced human adipose-derived stem cells (hADSCs) by this construct via a lentiviral vector (PCDH-513B). We assessed the ability of long-term expression of the transgene in transduced cells by western blot analysis and enzyme-linked immunosorbent assay techniques on Days 15, 45, and 75 after transduction. For the evaluation of stem cell properties, flow cytometry and differentiation assays were performed. Finally, the MTT assay was done to assess the proliferation of transduced cells compares to controls. Our results showed high-efficiency transduction with highest expression rates on Day 75 after transduction which were 70 pg/ml for IFN-β and 77.9 pg/ml for LIF in comparison with 25.60 pg/ml and 27.63 pg/ml, respectively, in untransduced cells (p = .0001). Also, transduced cells expressed a high level of ADSCs surface markers and successfully differentiated into adipocytes, chondrocytes, neural cells, and osteocytes besides the preservation rate of proliferation near untreated cells (p = .88). All in all, we successfully constructed an hADSC population stably overexpressed IFN-β and LIF cytokines. Considering the IFN-β and LIF anti-inflammatory and neuroprotective effects as well as immune-regulatory properties of hADSCs, the obtained cells of this study could be subjected for further evaluations in experimental autoimmune encephalomyelitis mice model. 相似文献
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95.
Francesca Re Ilaria Cambianica Silvia Sesana Elisa Salvati Alfredo Cagnotto Mario Salmona Pierre-Olivier Couraud S. Moein Moghimi Massimo Masserini Giulio Sancini 《Journal of biotechnology》2011,156(4):341
Nanoliposomes containing phosphatidic acid or cardiolipin are able to target in vitro with very high affinity amyloid-β (Aβ), a peptide whose overproduction and progressive aggregation in the brain play a central role in the pathogenesis of Alzheimer's disease. However, the presence of the blood–brain barrier (BBB) severely limits the penetration of either drugs or drug vehicles (nanoparticles) to the brain. Therefore, there is a need to develop and design approaches specifically driving nanoparticles to brain in a better and effective way. The aim of the present investigation is the search of a strategy promoting the interaction of liposomes containing acidic phospholipids with brain capillary endothelial cells, as a first step toward their passage across the BBB. We describe the preparation and physical characterization of nano-sized liposomes decorated with peptides derived from apolipoprotein E and characterize their interaction with human immortalized brain capillary cells cultured in vitro (hCMEC/D3). For this purpose, we synthesized two ApoE-derived peptides (the fragment 141–150 or its tandem dimer) containing a cysteine residue at the C-terminus and decorated NL by exploiting the cysteine reaction with a maleimide-group on the nanoparticle surface. NL without ApoE functionalization did not show either relevant membrane accumulation or cellular uptake, as monitored by confocal microscopy using fluorescently labeled nanoliposomes or quantifying the cell-associated radioactivity of isotopically labeled nanoliposomes. The uptake of nanoliposomes by cell monolayers was enhanced by ApoE-peptide-functionalization, and was higher with the fragment 141–150 than with its tandem dimer. The best performance was displayed by nanoliposomes containing phosphatidic acid and decorated with the ApoE fragment 141–150. Moreover, we show that the functionalization of liposomes containing acidic phospholipids with the ApoE fragment 141–150 scarcely affects their reported ability to bind Aβ peptide in vitro. These are important and promising features for the possibility to use these nanoliposomes for the targeting of Aβ in the brain districts. 相似文献
96.
Khani Soghra Seyedjavadi Sima Sadat Hosseini Hamideh Mahmoodzadeh Goudarzi Mehdi Barzegari Mina Khatami Shohreh Ajdary Soheila Eslamifar Ali Amani Jafar Imani Fooladi Abbas Ali Razzaghi-Abyaneh Mehdi 《International journal of peptide research and therapeutics》2021,27(3):1967-1977
International Journal of Peptide Research and Therapeutics - DiSkh-AMP1, a novel dimeric antifungal peptide contained 65 amino acid residues was recombinant produced by a flexible linker to improve... 相似文献
97.
Plasmonics - Magnetooptical Faraday effect enables ultrafast photonic devices based on nonreciprocal polarization rotation; however, the intrinsic weakness of Faraday effect prevents... 相似文献
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99.
Ajdary S Ghamilouie MM Alimohammadian MH Riazi-Rad F Pakzad SR 《Microbes and infection / Institut Pasteur》2011,13(3):226-231
The clinical spectrum of cutaneous leishmaniasis (CL) is extremely variable. Studies in experimental leishmaniasis have revealed a role for TLR4 in control of infection. In the present study the associations between TLR4 mutations (Asp299Gly and Thr399Ile) with outcome of CL have been investigated. Genotyping for Asp299Gly and Thr399Ile was performed in patients with chronic (N?=?22) and acute (N?=?61) CL, asymptomatic (N?=?45) and healthy leishmanin skin test negative individuals (N?=?75). The results showed the frequency of the Asp299Gly genotype was increased in patients with chronic disease (OR 25.3, 95% CI 5.2-115.6, P?0.001) and patients with acute disease (OR 8.03, 95% CI 1.7-37.7, P?=?0.006) compared to LST negative subjects. Thr399Ileu genotype was significantly over represented among patients with chronic disease (27.3%, P?0.001), patients with acute disease (13.1%, P?=?0.016), and asymptomatic donors (15.6%, P?=?0.008) in comparison with LST negative normal group (1.3%). Both variants were found together more frequently in patients with chronic disease compared to the patients with acute disease (P?=?0.045), and asymptomatic donors (P?=?0.045). The results provide evidence that polymorphisms of TLR4 gene may lead to the increased susceptibility to and severity of infection by Leishmania major. The concomitant carriage of both mutations increases the susceptibility of individuals to CL. 相似文献
100.
The interaction of native calf thymus DNA with ethylenediaminetetraaceticacid (EDTA) in Tris-HCl buffer at pH?=?7.8 (at this pH EDTA forms a disodium salt) was investigated. EDTA is widely used in medicine, food technology, and the chemical industry. The DNA binding mode of EDTA was monitored by absorption spectrophotometry, circular dichrosim, viscometry, and gel electrophoresis. Ultraviolet spectra of DNA showed small hyperchromicity with increase in EDTA concentration. The circular dichrosim signals at 245 and 280?nm indicated structural changes in DNA structure, and no significant effect on DNA viscosity was observed in the presence of increasing amounts of EDTA. Results are indicative of an outside, nonintercalative binding mode of EDTA to DNA. Moreover, gel electrophoresis studies showed considerable oxidative cleavage of plasmid DNA by EDTA. Mechanistic aspects of the chemical nuclease reactions were investigated using the OH radical quencher dimethylsulfoxide. In the presence of selenium, DNA cleavage by EDTA was inhibited. 相似文献