Brain‐derived neurotrophic factor (BDNF) is a well‐known neuroprotectant and a potent therapeutic candidate for neurodegenerative diseases. However, there are several clinical concerns about its therapeutic applications. In the current study, we designed and developed BDNF‐mimicking small peptides as an alternative to circumvent these problems. A phage‐displayed peptide library was screened using BDNF receptor (neurotrophic tyrosine kinase receptor type2 [NTRK2]) and evaluated by ELISA. The peptide sequences showed similarity to loop2 of BDNF, they were recognized as discontinuous epitopes though. Interestingly, in silico molecular docking showed strong interactions between the peptide three‐dimensional models and the surface residues of the NTRK2 protein at the IgC2 domain. A consensus peptide sequence was then synthesized to generate a mimetic construct (named as RNYK). The affinity binding and function of this construct was confirmed by testing against the native structure of NTRK2 in SH‐SY5Y cells in vitro using flow‐cytometry and MTT assays, respectively. RNYK at 5 ng/mL prevented neuronal degeneration of all‐ trans‐retinoic acid‐treated SH‐SY5Y with equal efficacy to or even better than BDNF at 50 ng/mL.
Glaucoma is a collective term used to define a group of neurodegenerative processes affecting the entire visual pathway best distinguished by progressive, irreversible destruction, and death of retinal ganglion cells (RGCs). The disease spectrum is estimated to affect more than 100 million people worldwide by the year of 2040 (Tham et al., 2014). The primary risk factor for progression and development of glaucoma is elevated intraocular pressure (IOP). IOP is regulated by the balance between aqueous humor secretion into
statement: Glaucoma-on-a-chip offers the advantages of allowing controlled experimental conditions, 15 preliminary targeting of a specific cell type or pathway involved in glaucoma and investigating putative 16 neuroprotective agents prior to assessment in animal models. 17 Abstract 18We developed a glaucoma-on-a-chip (GOC) model to evaluate the viability of retinal ganglion cells (RGCs) 19 against high pressure and neuroprotective treatments. A three-layered chip consisting of interconnecting 20 microchannels and culture wells was fabricated based on simulation of physical parameters. The bottom surface of 21 the wells was mechanically modified by air plasma and coated with different membranes to model an extracellular 22 microenvironment. SH-SY5Y used as model cells to determine the best supporting membrane which was revealed 23 to be PDL/laminin. RGCs were isolated from postnatal Wistar rats and purified by magnetic assisted cell sorting up 24 to 70%. The cultured RGCs were exposed to normal (15 mmHg) or elevated pressure (33 mmHg) for 6, 12, 24, 36 25 and 48 hours, with and without adding brain-derived-neurotrophic factor (BDNF) or a novel BDNF mimetic (named 26 RNYK). RGC survival rates were 85, 78, 70, 67 and 61% under normal pressure versus 40, 22, 18, 12 and 10% under 27 high pressure at 6, 12, 24, 36 and 48 hours, respectively (P<0.0001). BDNF and RNYK reduced the rate of RGC 28 death under both normal and elevated pressures, two-fold approximately (p<0.01-0.0001). 29 42 et al., 1995; Vecino and Sharma, 2011). Without sequential treatments, the duration of IOP elevation is 43 transient in these models. Precise control over IOP elevation is difficult and certain problems may occur; these include 44 intraocular inflammation, irreversible mydriasis, IOP variability, hyphema, reduced visibility of optic discs, corneal 45 opacity, and scleral burns (Johnson and Tomarev, 2010; Rudzinski and Saragovi, 2005). While in vivo animal models 46 are indispensable to determine what events occur in live organisms, these strategies typically involve poorly defined 47 377 Acevedo, A. D., Bowser, S. S., Gerritsen, M. E. and Bizios, R. (1993). Morphological and proliferative 378 responses of endothelial cells to hydrostatic pressure: role of fibroblast growth factor. Journal of Cellular Physiology. 379 157, 603-614. Shareef
An ongoing pandemic of coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). So far, there have been various approaches for SARS-CoV-2 detection, each having its pros and cons. The current gold-standard method for SARS-CoV-2 detection, which offers acceptable specificity and sensitivity, is the quantitative reverse transcription-PCR (qRT-PCR). However, this method requires considerable cost and time to transport samples to specialized laboratories and extract, amplify, and detect the viral genome. On the other hand, antigen and antibody testing approaches that bring rapidity and affordability into play have lower sensitivity and specificity during the early stages of COVID-19. Moreover, the immune response is variable depending on the individual. Methods based on clustered regularly interspaced short palindromic repeats (CRISPR) can be used as an alternative approach to controlling the spread of disease by a high-sensitive, specific, and low-cost molecular diagnostic system. CRISPR-based detection systems (CRISPR-Dx) target the desired sequences by specific CRISPR-RNA (crRNA)-pairing on a pre-amplified sample and a subsequent collateral cleavage. In the present article, we have reviewed different CRISPR-Dx methods and presented their benefits and drawbacks for point-of-care testing (POCT) of suspected SARS-CoV-2 infections at home or in small clinics.
A computational analysis of mixing of hydrogen and air has been performed considering scramjet (supersonic combustion ramjet) combustor. Hydrogen is injected at M=1 through the rear of a simple strut located at a distance of 37.54 mm from inlet of combustor. The shape of the strut is chosen in a way to produce strong streamwise vorticity and thus to enhance the hydrogen/air mixing. Strength and size of the vortices are defined by the strut geometry and may be modified. The induced vortices cause an increase in entropy and larger losses in total pressure.
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