Induction of Biologically Active Flavonoids in Cell Cultures of Morus nigra and Testing their Hypoglycemic Efficacy

The antidiabetic activity of both leaves and MJ-treated cell cultures of Morus nigra was evaluated after their oral administration to streptozotocin-induced diabetic rats. The antidiabetic activity of extracts from leaves given to streptozotocin (STZ)-diabetic rats for 10 days increased with increasing doses of leaves extract up to 500 mg/kg/day. The administration of 500 mg/kg/day of leaves extract reduced the concentration of glucose from 370 ± 7.31 mg/dl (control) to 154 ± 6.27 mg/dl, and a significant increase in the insulin level from 11.3 ± 0.31 μU/ml (control) to 14.6 ± 0.43 μU/ml was recorded. Cell suspension cultures were established from the young leaves of Morus nigra cultivated on modified MS medium supplemented with 2.0 mg/l 1-naphthaleneacetic acid (NAA), 0.2 mg/l 6-(furfurylamino)purine (kinetin). The changes in cell weight and flavonoid content were monitored between day zero and 12. The linear increase in fresh weight was found to be parallel to flavonoids production. Cell cultures treated with 100 μM methyl jasmonate for 24 hours showed a noticeable increase in level of flavonoids and significant and more effective hypoglycemic activity than that for extract from leaves. The major flavonoids were isolated by TLC and HPLC and identified as rutin, quercetin, Morusin and cyclomorusin by co-chromatography and mass spectrometry in comparison to samples of authentic reference compounds

Uncovering the Critical Drivers of Blockchain sustainability in higher education using a deep learning-based hybrid SEM-ANN approach

The increasing popularity of Blockchain technology has led to its adoption in various sectors, including higher education. However, the sustainability of Blockchain in higher education is yet to be fully understood. Therefore, this research examines the determinants affecting Blockchain sustainability by developing a theoretical model that integrates the protection motivation theory (PMT) and expectation confirmation model (ECM). Based on 374 valid responses collected from university students, the proposed model is evaluated through a deep learning-based hybrid structural equation modeling (SEM) and artificial neural network (ANN) approach. The PLS-SEM results confirmed most of the hypotheses in the proposed model. The sensitivity analysis outcomes discovered that users’ satisfaction is the most important factor affecting Blockchain sustainability, with 100% normalized importance, followed by perceived usefulness (58.8%), perceived severity (12.1%), and response costs (9.2%). The findings o

Monitoring and Assessing the Coastal Ecosystem at Hurghada, Red Sea Coast, Egypt

In the framework of the investment plan, the government of Egypt introduced an accelerated development of Hurghada in collaboration with the private sector, as   early as 1980's.  The government intended to construct tourist resort communities, which required establishment of infrastructures. The  demand  of  such  facilities, in absence of enforced environmental roles led owners  to implement  processes  of  landfilling  and  dredging  for the purpose of smoothing, paving and widening the beach in order to construct swimming pools, marinas and other recreational facilities. Such activities came on the expense of the marine ecosystem and especially assault on the coral reef communities. For monitoring and assessing such oppressive activities;  MSS,  TM,  ETM+,  and SPOT XS 4 satellite images acquired  during  1972,  1984,  1992,  2004  and 2011. Shoreline change detection from 1972 to 2011 reveals landfilling of some 7.56Km2 and dredging of 2.67km2, with loss of 5.34km2 of the reef tracts. At the same period, the region has witnessed expansions in urban and road network by 16.47km2 and 8.738km2 respectively. The Egyptian government issued the essential laws for regulating and saving the coastal ecosystem, yet mostly violated. Activation of such laws, applying judicial officers, toughening penalties and establishment of coastal building front line (CBFL), and a reef protection line (RPL) are important tasks especially south of Hurghada to the Egyptian-Sudanese borders to preserve the remnants of such unique coastal ecosystem. Keywords: Satellite images, Hurghada, Red Sea, coastal ecosystem, shoreline changes, urban, road network, environment law

New Diaryl-1,2,4-triazolo[3,4- a ]pyrimidine Hybrids as Selective COX-2/sEH Dual Inhibitors with Potent Analgesic/Anti-inflammatory and Cardioprotective Properties

COX-2-selective drugs were withdrawn from the market just a few years after their development due to cardiovascular side effects. As a result, developing a selective COX-2 inhibitor as an anti-inflammatory agent with cardioprotective characteristics has become a prominent objective in medicinal chemistry. New 15 diaryl-1,2,4-triazolo[3,4-a]pyrimidine hybrids 8a–o were synthesized and investigated in vitro as dual COX-2/sEH inhibitors. Compounds 8b, 8m, and 8o have the highest potency and selectivity as COX-2 inhibitors (IC$_{50}$ = 15.20, 11.60, and 10.50 μM, respectively; selectivity index (COX-1/COX-2) = 13, 20, and 25, respectively), compared to celecoxib (COX-2; IC$_{50}$ = 42 μM; SI = 8). The 5-LOX inhibitory activity of compounds 8b, 8m, and 8o was further examined in vitro. Compounds 8m and 8o, the most effective COX-2 selective inhibitors, demonstrated stronger 5-LOX inhibitory action than the reference quercetin, with IC$_{50}$ values of 2.90 and 3.05 μM, respectively. Additionally, compounds 8b, 8m, and 8o were the most potent dual COX-2/sEH inhibitors, with IC$_{50}$ values against sEH of 3.20, 2.95, and 2.20 nM, respectively, and were equivalent to AUDA (IC$_{50}$ = 1.2 nM). In vivo investigations also demonstrated that these compounds were the most efficacious as analgesic/anti-inflammatory derivatives with a high cardioprotective profile against cardiac biomarkers and inflammatory cytokines. The docking data analysis inquiry helped better understand the binding mechanisms of the most active hybrids within the COX-2 active site and supported their COX-2 selectivity. Compounds 8b, 8m, and 8o exhibited a similar orientation to rofecoxib and celecoxib, with a larger proclivity to enter the selectivity side pocket than the reference compounds

Combination of Human Amniotic Fluid Derived-Mesenchymal Stem Cells and Nano-hydroxyapatite Scaffold Enhances Bone Regeneration

BACKGROUND: Human amniotic fluid-derived stem cells (hAF-MSCs) have a high proliferative capacity and osteogenic differentiation potential in vitro. The combination of hAF-MSCs with three-dimensional (3D) scaffold has a promising therapeutic potential in bone tissue engineering and regenerative medicine. Selection of an appropriate scaffold material has a crucial role in a cell supporting and osteoinductivity to induce new bone formation in vivo. AIM: This study aimed to investigate and evaluate the osteogenic potential of the 2nd-trimester hAF-MSCs in combination with the 3D scaffold, 30% Nano-hydroxyapatite chitosan, as a therapeutic application for bone healing in the induced tibia defect in the rabbit. SUBJECT AND METHODS: hAF-MSCs proliferation and culture expansion was done in vitro, and osteogenic differentiation characterisation was performed by Alizarin Red staining after 14 & 28 days. Expression of the surface markers of hAF-MSCs was assessed using Flow Cytometer with the following fluorescein-labelled antibodies: CD34-PE, CD73-APC, CD90-FITC, and HLA-DR-FITC. Ten rabbits were used as an animal model with an induced defect in the tibia to evaluate the therapeutic potential of osteogenic differentiation of hAF-MSCs seeded on 3D scaffold, 30% Nano-hydroxyapatite chitosan. The osteogenic differentiated hAF-MSCs/scaffold composite system applied and fitted in the defect region and non-seeded scaffold was used as control. The histopathological investigation was performed at 2, 3, & 4 weak post-transplantation and scanning electron microscope (SEM) was assessed at 2 & 4 weeks post-transplantation to evaluate the bone healing potential in the rabbit tibia defect. RESULTS: Culture and expansion of 2nd-trimester hAF-MSCs presented high proliferative and osteogenic potential in vitro. Histopathological examination for the transplanted hAF-MSCs seeded on the 3D scaffold, 30% Nano-hydroxyapatite chitosan, demonstrated new bone formation in the defect site at 2 & 3 weeks post-transplantation as compared to the control (non-seeded scaffold). Interestingly, the scaffold accelerated the osteogenic differentiation of AF-MSCs and showed complete bone healing of the defect site as compared to the control (non-seeded scaffold) at 4 weeks post-transplantation. Furthermore, the SEM analysis confirmed these findings. CONCLUSION: The combination of the 2nd-trimester hAF-MSCs and 3D scaffold, 30% Nano-hydroxyapatite chitosan, have a therapeutic perspective for large bone defect and could be used effectively in bone tissue engineering and regenerative medicine

Bilosomes as a promising nanoplatform for oral delivery of an alkaloid nutraceutical:improved pharmacokinetic profile and snowballed hypoglycemic effect in diabetic rats

Diabetes mellitus is a life-threatening metabolic disease. At the moment, there is no effective treatment available to combat it. In this study, we aimed to develop berberine-loaded bilosomes (BER-BLS) to boost the oral bioavailability and therapeutic efficacy of berberine, a natural antidiabetic medication. The BER-BLS was fabricated using a thin-film hydration strategy and optimized using a central composite design (face-centered). The average vesicle size, entrapment efficiency, and surface charge of the optimized BER-BLS preparation were 196.5 nm, 89.7%, (−) 36.4 mV, respectively. In addition, it exhibited higher stability and better-sustained release of berberine than the berberine solution (BER-SOL). BER-BLS and BER-SOL were administered to streptozocin-induced diabetic rats. The optimized BER-BLS formulation had a significant hypoglycemic impact, with a maximum blood glucose decrease of 41%, whereas BER-SOL only reduced blood glucose by 19%. Furthermore, the pharmacological effect of oral BER-BLS and BER-SOL corresponded to 99.3% and 31.7%, respectively, when compared to subcutaneous insulin (1 IU). A pharmacokinetic analysis found a 6.4-fold rise in the relative bioavailability of berberine in BER-BLS when compared to BER-SOL at a dosage of 100 mg/kg body weight. Histopathological investigation revealed that BER-BLS is suitable for oral administration. Our data demonstrate that BLS is a potential nanocarrier for berberine administration, enhancing its oral bioavailability and antidiabetic activity

Genetic distance and heterogenecity between quasispecies is a critical predictor to IFN response in Egyptian patients with HCV genotype-4

BACKGROUND: HCV is one of the major health problems in Egypt, where it is highly prevalent. Genotype 4 is the most common genotype of HCV and its response to treatment is still a controversy. METHODS: HCV genotype 4 quasispecies diversity within the 5' untranslated region (5'UTR) was studied in a series of 22 native Egyptian patients with chronic hepatitis C virus with no previous treatment who satisfied all NIH criteria for combined treatment of pegylated IFN and ribavirine and was correlated with the outcome of treatment. The study also included 7 control patients with no antiviral treatment. HCV sequencing was done using the TRUGENE HCV 5-NC genotyping kit. RESULTS: At the 48(th )week of treatment, 15 patients (68%) showed virological response. Whereas HCV-RNA was still detected in 7 patients (32%) in this period; of those, 6 experienced a partial virological response followed by viral breakthrough during treatment. Only one patient did not show any virological or chemical response. The four females included in this study were all responders. There was a significant correlation between the response rate and lower fibrosis (p = 0.026) as well as the total number of mutation spots (including all the insertions, deletions, transitions and transversions) (p = 0.007, p = 0.035). CONCLUSION: Patients who responded to interferon treatment had statistically significant less number in both transitions (p = 0.007) and the genetic distances between the quasispecies (p = 0.035). So, viral genetic complexity and variability may play a role in the response to IFN treatment. The consensus alignment of all three groups revealed no characteristic pattern among the three groups. However, the G to A transitions at 160 was observed among non responders who need further study to confirm this observation

Case Report: Guillain–Barré Syndrome Associated With COVID-19

Guillain–Barré syndrome (GBS) is a potentially fatal, immune-mediated disease of the peripheral nervous system that is usually triggered by infection. Only a small number of cases of GBS associated with COVID-19 infection have been published. We report here five patients with GBS admitted to the Neurology, Psychiatry, and Neurosurgery Hospital, Assiut University/Egypt from July 1 to November 20, 2020. Three of the five patients were positive for SARS-CoV-2 following polymerase chain reaction (PCR) of nasopharyngeal swabs on day of admission and another one had a high level of IgM and IgG; all had bilateral ground-glass opacities with consolidation on CT chest scan (GGO) and lymphopenia. All patients presented with two or more of the following: fever, cough, malaise, vomiting, and diarrhea with variable duration. However, there were some peculiarities in the clinical presentation. First, there were only 3 to 14 days between the onset of COVID-19 symptoms and the first symptoms of GBS, which developed into flaccid areflexic quadriplegia with glove and stocking hypoesthesia. The second peculiarity was that three of the cases had cranial nerve involvement, suggesting that there may be a high incidence of cranial involvement in SARS-CoV-2-associated GBS. Other peculiarities occurred. Case 2 presented with a cerebellar hemorrhage before symptoms of COVID-19 and had a cardiac attack with elevated cardiac enzymes following onset of GBS symptoms. Case 5 was also unusual in that the onset began with bilateral facial palsy, which preceded the sensory and motor manifestations of GBS (descending course). Neurophysiological studies showed evidence of sensorimotor demyelinating polyradiculoneuropathy, suggesting acute inflammatory polyneuropathy (AIDP) in all patients. Three patients received plasmapheresis. All of them had either full recovery or partial recovery. Possible pathophysiological links between GBS and COVID-19 are discussed

Neutralizing activities of caprine antibodies towards conserved regions of the HCV envelope glycoprotein E2

Anti HCV vaccine is not currently available and the present antiviral therapies fail to cure approximately half of the treated HCV patients. This study was designed to assess the immunogenic properties of genetically conserved peptides derived from the C-terminal region of HVR-1 and test their neutralizing activities in a step towards developing therapeutic and/or prophylactic immunogens against HCV infection. Antibodies were generated by vaccination of goats with synthetic peptides derived from HCV E2. Viral neutralizing capacity of the generated anti E2 antibodies was tested using in vitro assays. Goats immunized with E2 synthetic peptides termed p412 [a.a 412-419], p430 [a.a 430-447] and p517 [a.a 517-531] generated high titers of antibody responses 2 to 4.5 fold higher than comparable titers of antibodies to the same epitopes in chronic HCV patients. In post infection experiments of native HCV into cultured Huh7.5 cells anti p412 and anti p 517 were proven to be neutralizing to HCV genotype 4a from patients' sera (87.5% and 75% respectively). On the contrary anti p430 exhibited weak viral neutralization capacity on the same samples (31.25%). Furthermore Ab mixes containing anti p430 exhibited reduced viral neutralization properties. From these experiments one could predict that neutralization by Abs towards different E2-epitopes varies considerably and success in the enrichment of neutralization epitope-specific antibodies may be accompanied by favorable results in combating HCV infection. Also, E2 conserved peptides p517 and p412 represent potential components of a candidate peptide vaccine against HCV infection

Solving vehicle routing problem by using improved K-nearest neighbor algorithm for best solution

Vehicle routing problem (VRP) is one of the many difficult issues that have no perfect solutions yet. Many researchers over the last few decades have established numerous researches and used many methods with different techniques to handle it. But, for all research, finding the lowest cost is very complex. However, they have managed to come up with approximate solutions that differ in efficiencies depending on the search space. Problem: In this study the problem is as follows: have a number of vehicles which are used for transporting applications to instance place. Each vehicle starts from a main location at different times every day. The vehicle picks up applications from start locations to the instance place in many different routes and return back to the start location in at specific times every day, starting from early morning until the end of official working hours, on the following conditions: (1) Every location will be visited once in each route, and (2) The capacity of each vehicle is enough for all applications included in each route. Objectives: Our paper attempt to find an optimal route result for VRP by using K-Nearest Neighbor Algorithm (KNNA). To achieve an optimal solution for VRP with the accompanying targets: (1) To reduce the distance and the time for all paths this leads to speedy the transportation of customers to their locations, (2) To implement the capacitated vehicle routing problem (CVRP) model for optimizing the solutions. Approach: The approach has been presented based on two phases: firstly, the algorithms have been adapted to solve the research problem, where its procedure is different than the common algorithm. The structure of the algorithm is designed so that the program does not require a large database to store the population, which speeds up the implementation of the program execution to obtain the solution; secondly, the algorithm has proven its success in solving the problem and finds a shortest route. For the purpose of testing the algorithm’s capability and reliability, it was applied to solve the same problem online validated and it achieved success in finding a shorter route. Finding: The findings outcome from this study have shown that: (1) A universal listed of dynamic KNNACVRP; (2) Identified and built up an assessment measure for KNNACVRP; (3) Highlight the strategies, based KNNA operations, for choosing the most ideal way (4) KNNA finds a shorter route for VRP paths. The extent of lessening the distance for each route is generally short, but the savings in the distance becomes more noteworthy while figuring the aggregate distances traveled by all transports day by day or month to month. This applies likewise to the time calculate that has been decreased marginally in view of the rate of reduction in the distances of the paths