Biology subjects

Shalaby, M.

Publications and source records attributed to Shalaby, M..

4 recordsLinked to original sources

bioRxiv2026

ESCRT-I Inhibition Protects against NMDAR Hypofunction and Restores Synaptic Homeostasis in a Cellular Model of Schizophrenia

N-methyl-D-aspartate receptor (NMDAR) hypofunction is a central pathophysiological mechanism in schizophrenia, yet direct NMDAR potentiation has shown limited clinical benefit, potentially because it fails to address deficits in receptor trafficking and surface stability. The endosomal sorting complexes required for transport (ESCRT) machinery governs the lysosomal fate of internalised membrane proteins, but its role in synaptic receptor homeostasis during glutamatergic dysfunction remains unclear. Phencyclidine (PCP), a non-competitive NMDAR antagonist, is widely used to model NMDAR hypofunction and schizophrenia-like phenotypes. Here, we show that sub-chronic PCP exposure induced persistent NMDAR hypofunction, impaired GABAergic transmission, and collapsed of excitation/inhibition (E/I) balance in primary hippocampal neurons. Genetic inhibition of the ESCRT-I component TSG101 prevented these deficits, enabled functional recovery following PCP washout, and increased surface expression of functional NMDARs and GABAA receptors without altering receptor pharmacology or biophysical properties. At the network level, TSG101 knockdown restored inhibitory tone, normalised excitatory activity, and stabilised E/I balance. Moreover, TSG101 knockdown rescued PCP-induced reductions in PSD-95 and BDNF, restored ERK1/2 signalling, and re-established activity-dependent nuclear translocation of Fos-like (Fos-L), consistent with reactivation of transcriptional plasticity. These findings identify ESCRT-I as a regulator of synaptic stability, positioning endosomal sorting pathways as a potential therapeutic target for schizophrenia.

neuroscience↗

bioRxiv2023

Characterization of the RBM15 protein binding with XCI-escaping long noncoding RNAs

The RNA binding motif 15 protein (RBM15) plays a critical role in post-transcriptional regulation. Its role in facilitating N6-methyladenosine (m6A) modification, specifically through guiding the writer complex (WTAP METTL13 METTL14) to DRACH sequence motifs, has been demonstrated for several classes of RNA, including long noncoding RNAs (lncRNAs). The structural mechanism that underlies how RBM15 interacts with RNA has yet to be elucidated. In this study, we mined and bioinformatically assessed publicly available genome-wide RNA 2D structural probing and RBP cross-linking and immunoprecipitation data to investigate how RBM15 interacts with RNA, with a focus on lncRNA transcripts. RBM15, which possesses three RNA recognition motifs (RRMs), primarily interacts with stem-loop structured RNA motifs. Structural modeling reveals RRMs 2 and 3 are coaxially stacked in solution; these two RRMs are responsible for driving RBM15s interaction with RNA. We further demonstrate this experimentally with two RNA hairpins, revealing low micromolar binding affinities. Altogether, this work provides insight into the structural mechanism by which RBM15 interacts with RNAs to govern biological function.

biochemistry↗

bioRxiv2023

Nanoparticles of bioactive natural collagen for wound healing: Experimental approach

IntroductionBoth developing and developed nations have made the creation of innovative wound-healing nanomaterials based on natural extracts a top research goal. The objective of this research was to create a gel containing collagen nanoparticles and evaluate its therapeutic potential for skin lesions. MethodsCollagen nanoparticles from fish scales were produced for the first time using desolvation techniques. Using Fourier transform infrared spectroscopy (FTIR), the structure of the isolated collagen and its similarities to collagen type 1 were identified. The surface morphology of the isolated collagen and its reformulation into nanoparticles were examined using transmission and scanning electron microscopy. Human skin fibroblast cells were employed to examine the cytotoxicity of the nanomaterials, and an experimental model was used to evaluate the wound healing capability. ResultsCollagen nanoparticles formulation was confirmed using FTIR, SEM and TEM analysis. Cytotoxicity studies demomstrated that the manufactured nanoparticles have minor toxicity at high concentrations on human skin fibroblast. Histological investigation proved that the fabricated fish scale collagen nanoparticles promoted the healing process in comparison to the saline group. ConclusionThe fabricated product is a highly influential wound healing product that can be applicable for commercial use. The nanoscale size of collagen nanoparticles, make them interesting candidates for biological applications. Key Summary PointsO_LIThe goal of this research was to create natural, effective wound remedies that could lower health-care costs while also providing pain relief and, ultimately, effective scar repair. C_LIO_LICollagen nanoparticles can be synthesized from fish scale utilizing various nanotechnology-based approaches to stimulate skin cell proliferation and promote wound healing. C_LIO_LICollagen nanoparticles have a rough surface, have a negative potential, and can be used for drug delivery and wound healing. C_LIO_LIHistological and macroscopical analysis showed that the synthesized nanoparticles promoted faster wound healing. C_LI

synthetic biology↗

bioRxiv2019

The Arabian camel, Camelus dromedarius interferon epsilon: functional expression, in vitro refolding, purification and cytotoxicity on breast cancer cell lines MDA-MB-231 and MCF-7

The current study highlights for the first time cloning, overexpression, purification, and assessing the cytotxcity of the novel interferon epsilon (IFN{varepsilon}), from the Arabian camel Camelus dromedarius, against two human breast cancer cell lines MDA-MB-231 and MCF-7. Full-length cDNA encoding interferon epsilon (IFN{varepsilon}) was isolated and cloned from the liver of the Arabian camel, C. dromedarius using reverse transcription-polymerase chain reaction. The sequence analysis of the camel IFN{varepsilon} cDNA showed a 582-bp open reading frame encoding a protein of 193 amino acids with an estimated molecular weight of 22.953 kDa. A BLAST search analysis revealed that the C. dromedarius IFN{varepsilon} shared high sequence identity with the IFN genes of other species, such as Camelus ferus, Vicugna pacos, and Homo sapiens. Expression of the camel IFN{varepsilon} cDNA in Escherichia coli gave a fusion protein band of 22.73 kDa after induction with either isopropyl {beta}-D-1-thiogalactopyranoside or lactose for 5 h. Recombinant IFN{varepsilon} protein was overexpressed in the form of inclusion bodies that were easily solubilized and refolded using SDS and KCl. The solubilized inclusion bodies were purified to apparent homogeneity using nickel affinity chromatography. We examined the effect of IFN{varepsilon} on two breast cancer cell lines MDA-MB-231 and MCF-7. In both cell lines, IFN{varepsilon} inhibited cell survival in a dose dependent manner as observed by MTT assay, morphological changes and apoptosis assay. Caspase-3 expression level was found to be increased in MDA-MB-231 treated cells as compared to untreated cells.

molecular biology↗