Self-Assembled Lipoplexes of Short Interfering RNA (siRNA) Using Spermine-Based Fatty Acid Amide Guanidines: Effect on Gene Silencing Efficiency

Four guanidine derivatives of N4,N9-diacylated spermine have been designed, synthesized, and characterized. These guanidine-containing cationic lipids bound siRNA and formed nanoparticles. Two cationic lipids with C18 unsaturated chains, N1,N12-diamidino-N4,N9-dioleoylspermine and N1,N12-diamidino-N4-linoleoyl-N9-oleoylspermine, were more efficient in terms of GFP expression reduction compared to the other cationic lipids with shorter C12 (12:0) and very long C22 (22:1) chains. N1,N12-Diamidino-N4-linoleoyl-N9-oleoylspermine siRNA lipoplexes resulted in GFP reduction (26%) in the presence of serum, and cell viability (64%). These data are comparable to those obtained with TransIT TKO. Thus, cationic lipid guanidines based on N4,N9-diacylated spermines are good candidates for non-viral delivery of siRNA to HeLa cells using self-assembled lipoplexes

Identification of Novel Argonaute Proteins Using a Metagenomic Mining Approach

Gene editing is one of the most promising tools in science. It enables precise modifications of an organism\u27s genetic material. Metagenomics is considered a powerful tool that unlocks the broad genetic potential found in uncultured microbial communities. Exploring the genetic diversity of uncultured microbial communities helps identify novel functional proteins with unique properties and make the best use of these diverse microbial ecosystems. We developed and employed a metagenomic-based approach to mine more than 1000 metagenomes for prokaryotic argonaute proteins (pAgos), a potential gene editing machinery encoded in bacterial and archaeal genomes. Our workflow involved strict quality control, sequence assembly, taxonomic classification, profiling and analysis, and annotation. We then identified the presence of key domains such as PIWI and MID. Our methodology ensured effective screening and identification of these proteins across metagenomes from 25 different ecosystems. We analyzed 1,011 publicly available metagenomic datasets from which we identified 905 putative pAgos across these diverse environments by building a custom Hidden Markov Model (HMM) profile. Our analysis identified proteins with substantial diversity and considerable abundance in diverse microbial environments and included novel variants with unique functional characteristics. Our work highlights the power of metagenomics to discover novel functional proteins and presents promising applications for gene editing

A Free Exchange e-Marketplace for Digital Services

The digital era is witnessing a remarkable evolution of digital services. While the prospects are countless, the e-marketplaces of digital services are encountering inherent game-theoretic and computational challenges that restrict the rational choices of bidders. Our work examines the limited bidding scope and the inefficiencies of present exchange e-marketplaces. To meet challenges, a free exchange e-marketplace is proposed that follows the free market economy. The free exchange model includes a new bidding language and a double auction mechanism. The rule-based bidding language enables the flexible expression of preferences and strategic conduct. The bidding message holds the attribute-valuations and bidding rules of the selected services. The free exchange deliberates on attributes and logical bidding rules for automatic deduction and formation of elicited services and bids that result in a more rapid self-managed multiple exchange trades. The double auction uses forward and reverse generalized second price auctions for the symmetric matching of multiple digital services of identical attributes and different quality levels. The proposed double auction uses tractable heuristics that secure exchange profitability, improve truthful bidding and deliver stable social efficiency. While the strongest properties of symmetric exchanges are unfeasible game-theoretically, the free exchange converges rapidly to the social efficiency, Nash truthful stability, and weak budget balance by multiple quality-levels cross-matching, constant learning and informs at repetitive thick trades. The empirical findings validate the soundness and viability of the free exchange

A new model for early diagnosis of alzheimer's disease based on BAT-SVM classifier

Magnetic Resonance Images (MRI) of the Brain is a significant tool to diagnosis Alzheimer's disease due to its ability to measure regional changes in the brain that reflect disease progression to detect early stages of the disease. In this paper, we propose a new model that adopts Bat for parameter optimization problem of Support vector machine (SVM) to diagnose Alzheimer’s disease via MRI biomedical image. The proposed model uses MRI for biomedical image classification to diagnose three classes; normal controls (NC), mild cognitive impairment (MCI) and Alzheimer’s disease (AD). The proposed model based on segmentation for the most involved areas in the disease hippocampus, the features of MRI brain images are extracted to build feature vector of the brain, then extracting the most significant features in neuroimaging to reduce the high dimensional space of MRI images to lower dimensional subspace, and submitted to machine learning classification technique. Moreover, the model is applied on different datasets to validate the efficiency which show that the new Bat-SVM model can yield promising acceptable level of accuracy reached to 95.36 % using maximum number of bats equal to 50 and number of generation equal to 10

EFFECT OF OILS, SURFACTANTS AND COSURFACTANTS ON PHASE BEHAVIOR AND PHYSICOCHEMICAL PROPERTIES OF SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEM (SNEDDS) FOR IRBESARTAN AND OLMESARTAN

Objective: The main purpose of this study was to optimize the different conditions for the preparation of self-nanoemulsifying drug delivery system (SNEDDS) for both Irbesartan (IRB) and Olmesartan (OLM). Methods: Based on solubility study and emulsification efficiency, Preliminary investigations of various oils, surfactants and cosurfactants were carried out for selection of the proper SNEDDS ingredients. Pseudoternary phase diagrams were then plotted using series of concentrations to obtain optimum SNEDDS components that identify the efficient self-nanoemulsifying region. Sixteen unloaded SNEEDS formulae were prepared using Capryol 90, Cremophor RH 40 and Transcutol HP as oil, surfactant and cosurfactant respectively. The prepared SNEDDS were evaluated for self-nanoemulsification time, the effect of dilution (with different volumes at different pH values), optical clarity, viscosity, droplet size analysis as well as the polydispersity index (PDI). SNEDDS formulae were also evaluated for thermodynamic stability and zeta potential to confirm the stability of the prepared SNEDDS. Results: The results showed that the mean droplet size of all reconstituted SNEDDS was found to be in the nanometric range (<100 nm) and showed optimum PDI values. All formulae also showed rapid emulsification time, good optical clarity and found to be highly stable. Formulae with the smallest particle size, lowest emulsification time, best optical clarity and robust to dilution and pH change were selected to be loaded with IRB and OLM for further study. Conclusion: It was concluded that the prepared self-emulsified prototype was ready to incorporate many poorly soluble drugs in order to improve their solubility as well as bioavailability profile. Keywords: Irbesartan, Olmesartan, Self-nanoemulsifying drug delivery system (SNEDDS), Capryol 90, Cremophor RH 40 and Transcutol HP

Identification and detection of antibiotic susceptibility of the most common anerobes causing infection in surgical hospital, Faculty of Medicine Zagazig University, Egypt

Objectives: Anaerobic infections are considered to be the most difficult organisms to be identified in the microbiology laboratory. It requires strict conditions, proper sampling , long time and laboratory skills. In addition most of them are mixed infections having both aerobic and anaerobic organisms. Choice of the proper antibiotic for treating these anaerobes is live saving for the patient.Methods: Identification of anaerobic organisms using MALDI-TOF (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry) as a recent tool for identification together with API 20A (as a reference method). Antibiotic susceptibility test was done for the anaerobic isolates using Agar Dilution Method. With the the most commonly used antibiotic in our hospital which are Amoxacillin/Clavulonic acid, clindamycin, metronidazole and Imipenem.Results: Anaerobic infections constitutes 21.7% of total 249 specimen from different surgical departments. Bacteroids spp. (41%) were the most prevalent anaerobic organisms followed by peptostreptococcus (26.9%). MALDI TOF MS system and API achieved 100% agreement for identification of Porphoryomonas spp. and Fusobacterium, while near results were obtained for other isolates. Bacteroid spp. shows the highest rate of resistance to clindamycin (69%). Excellent results were obtained for Imipenem and metronidazole. Most of resistance to Amoxacillin/Clavulonic acid is related to Bacteroid spp. and Fusobacterium spp.Conclusion: MALDI TOF MS System is a useful tool for identification of. Anerobes are showing higher rates of resistance to commonly used antibiotics thus detection of resistant strains is vital for proper selection of antibiotics.Keywords: Anaerobes, MALDI TOF System, API 20, Agar Dilution Method, Zagazi

The Epidemiology of Circulating Rotavirus Associated with Diarrhea in Egyptian Kids and Calves: A Review

Acute gastroenteritis (AGE) induced by rotavirus has been a major disease burden in Egypt since 1981 when rotavirus was first reported in humans and calves. Genome segmentation facilitates the emergence of new virus serotypes, which allows reassortment during mixed infections, and is a characteristic feature of the family Reoviridae to which rotavirus belongs. The rotavirus genome involves 11 double-stranded RNA gene segments encoding 6 non-structural (NSP1–6) and 6 structural (VP1–4, VP6, VP7) proteins. Rotavirus A has a zoonotic potential associated with diarrhea. The primary strategy for prevention and control of bovine and human rotavirus infections is vaccination; however, routine rotavirus vaccination has not been implemented in the National Immunization Program. We evaluated studies published over the last 30 years that pertained to the epidemiology of circulating rotavirus genotypes among children, calves, and environmental samples in Egypt. The analysis revealed a rotavirus prevalence of 15%–100%, with diarrhea occurring throughout the year, but generally peaking during the cold months. G1 was the predominant genotype in children, followed by G2, G3, G4, G8, G9, and G12 throughout the study duration. Mixed infections were also detected. G6 was the predominant genotype in calves, followed by G10. There are still gaps in knowledge regarding molecular data of rotavirus infections in humans, animals, and environmental samples in Egypt, as well as the zoonotic potential of rotavirus disease. Therefore, it is critical to continue rotavirus surveillance in Egypt to further understand the epidemiology of rotavirus infections and the emerging new genotypes