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Abstract Alzheimer's, Parkinson’s, and Huntington’s are the most common neurodegenerative diseases that are incurable and affect the elderly population. Discovery of effective treatments for these diseases is often difficult, expensive, and serendipitous. Previous comparative studies on different model organisms have revealed that most animals share similar cellular and molecular characteristics. The meta-SNP tool includes four different integrated tools (SIFT, PANTHER, SNAP, and PhD-SNP) was used to identify non synonymous single nucleotide polymorphism (nsSNPs). Prediction of nsSNPs was conducted on three representative proteins for Alzheimer's, Parkinson’s, and Huntington’s diseases; APPl in Drosophila melanogaster, LRRK1 in Aedes aegypti, and VCPl in Tribolium castaneum. With the possibility of using insect models to investigate neurodegenerative diseases. We conclude from the protein comparative analysis between different insect models and nsSNP analyses that D. melanogaster is the best model for Alzheimer’s representing five nsSNPs of the 21 suggested mutations in the APPl protein. Aedes aegypti is the best model for Parkinson’s representing three nsSNPs in the LRRK1 protein. Tribolium castaneum is the best model for Huntington’s disease representing 13 SNPs of 37 suggested mutations in the VCPl protein. This study aimed to improve human neural health by identifying the best insect to model Alzheimer's, Parkinson’s, and Huntington’s.

Abstract Diabetes mellitus (DM) represents a major health problem in Egypt and worldwide, with increasing numbers of patients with prediabetes every year. Numerous factors, such as obesity, hyperlipidemia, and hypertension, which have recently become serious concerns, affect the complex pathophysiology of diabetes. These metabolic syndrome diseases are highly linked to genetic variability that drives certain populations, such as Egypt, to be more susceptible to developing DM. Here we conduct a comprehensive analysis to pinpoint the similarities and uniqueness among the Egyptian genome reference and the 1000-genome subpopulations (Europeans, Ad-Mixed Americans, South Asians, East Asians, and Africans), aiming at defining the potential genetic risk of metabolic syndromes. Selected approaches incorporated the analysis of the allele frequency of the different populations’ variations, supported by genotypes’ principal component analysis. Results show that the Egyptian’s reference metabolic genes were clustered together with the Europeans’, Ad-Mixed Americans’, and South-Asians’. Additionally, 8563 variants were uniquely identified in the Egyptian cohort, from those, two were predicted to cause structural damage, namely, CDKAL1: 6_21065070 (A > T) and PPARG: 3_12351660 (C > T) utilizing the Missense3D database. The former is a protein coding gene associated with Type 2 DM while the latter is a key regulator of adipocyte differentiation and glucose homeostasis. Both variants were detected heterozygous in two different Egyptian individuals from overall 110 sample. This analysis sheds light on the unique genetic traits of the Egyptian population that play a role in the DM high prevalence in Egypt. The proposed analysis pipeline -available through GitHub- could be used to conduct similar analysis for other diseases across populations.

Abstract In the present work, single wall carbon nanotubes (SWCNT) were successively functionalized with phospholipid DSPE-PEG carboxylic acid, and then, with ethylenediamine (EDA), to obtain double functionalized single wall carbon nanotube (DFSWCNT). Then, DFSWCNT was applied as a carrier for delivering amphotericin B (Amb) and EGFP plasmid. FSWCNT’s concentration obtained via UV–visible analysis was 0.99 mg/mL. The TGA analysis results provided the lost weights of DSPE-PEG-COOH, EDA, Amb and SWCNT impurities. XPS results showed that carbon atoms’ percentage decreased during the functionalization processes from 97.2% (SWCNT) to 76.4% (FSWCNT) and 69.9% (DFSWNCT). Additionally, the oxygen atoms’ percentage increased from 2.3% (SWCNT) to 21% and 22.5% for FSWCNT and DFSWCNT, respectively. New bonds such as C–N and N–C=O appeared in the synthesized nanocarrier. The IG/ID ratio in Raman analysis decreased from 7.15 (SWCNT) to 4.08 (FSWCNT). The amount of Amb released to phosphate buffer saline medium was about 33% at pH = 5.5 and 75% at pH = 7.4 after 48 h. CCK8 results confirmed that the toxicity of functionalized SWCNT had decreased. In a 2:1 ratio of DFSWCNT/EGFP plasmid, the cell viability (87%) and live transfected cells (56%) were at their maximum values. The results indicate that carbon nanotubes have the potential to be applied as drug/gene delivery systems with outstanding properties such as high loading capacity and easy penetration to cell membrane.

Abstract Relapsing Remitting Multiple Sclerosis is a chronic Central nervous system autoimmune disease. There is no absolute treatment for MS and the available remedies are called disease modifying therapies (DMTs). Glatiramer acetate (GA) is one of the FDA approved DMTs. Currently, injection-site problems and unfavorable daily injection are the most common milestones in administration of GA. So that, the design of improved drug delivery systems with sustained release profile seem necessary and helpful in order to minimize GA adverse effects and improve patients’ compliance. In this study, we have manufactured a novel chitosan-PLGA (poly (lactic-co-glycolic acid)) hydrogel-microparticles containing GA by double emulsion method. Hydrogel-microparticles’ properties including size, morphology and GA loading were investigated. In-vitro drug release was studied during 30 days. In vivo efficacy of GA-hydrogel-microparticles was evaluated in experimental autoimmune encephalomyelitis (EAE) as an established animal model for MS. Pathological studies were performed through H&E (Hematoxylin and Eosin) staining of brain, spine, liver, skin and kidney tissues. Luxol fast blue staining of brain tissue was also done. The obtained results were applied for safety and efficacy evaluations. GA loading and Entrapment efficiency (EE %) of 60% and 95% were achieved, respectively. In- vitro release studies confirms a sustained release profile for GA-hydrogel-microparticles. Mean clinical scores and mean body weights obtained from EAE animal model for GA-hydrogel-microparticles were compared to the outcomes achieved from conventional Iranian brand-generic injection solution of GA (Copamer®, 20 mg/ml). EAE outcomes and pathological studies confirm similar therapeutic efficacy with longer dosing intervals possibility, improved safety through decreased adverse effects and elimination of site injection reactions for GA-hydrogel-microparticles. Further studies on pharmacokinetic and pharmacodynamics in human volunteers are still required to thoroughly examine different aspects of this newly developed GA- hydrogel-microparticles.

Abstract Microbial nitrogen transformation processes such as denitrification represent major sources of the potent greenhouse gas nitrous oxide (N2O). Soil biochar amendment has been shown to significantly decrease N2O emissions in various soils. However, the effect of biochar on the structure and function of microbial communities that actively perform nitrogen redox transformations has not been studied in detail yet. To analyse the community composition of actively denitrifying and N2O-reducing microbial communities, we collected RNA samples at different time points from a soil microcosm experiment conducted under denitrifying conditions and performed Illumina amplicon sequencing targeting nirK, typical nosZ and atypical nosZ mRNA transcripts. Within 10 days, biochar significantly increased the diversity of nirK and typical nosZ transcripts and resulted in taxonomic shifts among the typical nosZ-expressing microbial community. Furthermore, biochar addition led to a significant increase in transcript production among microbial species that are specialized on direct N2O reduction from the environment. Our results point towards a potential coupling of biochar-induced N2O emission reduction and an increase in microbial N2O reduction activity among specific groups of typical and atypical N2O reducers. However, experiments with other soils and biochars will be required to verify the transferability of these findings to other soil-biochar systems.