Inhibition of macromolecular synthesis in cultured macrophages by Pseudomonas pseudomallei exotoxin

Pseudomonas pseudomallei exotoxin was found to be a potent inhibitor of protein and DNA synthesis in cultured macrophages. Inhibition of DNA synthesis occurred at toxin concentrations as low as 1-2 micrograms/ml and inhibition of 3H-thymidine uptake was almost complete at concentrations of 8 micrograms/ml or more. A close correlation between cell damage and inhibition by DNA synthesis was observed. For protein synthesis, inhibition was obtained at much lower doses (0.06-2.0 micrograms/ml) of the toxin. At similar toxin concentrations, DNA synthesis was marginally affected. Further, it was shown that protein synthesis inhibition occurred almost immediately after incubation, reaching its maximal inhibitory effect of 70% after 6 hr. DNA synthesis, however, was minimally affected by a similar toxin concentration even after 10 hr of incubation. The inhibition of macromolecular synthesis in macrophages by P. pseudomallei exotoxin may be relevant to its modulatory effect on the host defense mechanism.     

The dorsalis pedis myofascial flap

A modification of the dorsalis pedis artery island flap is presented. In this modification, the deep fascia of the dorsum of the foot with part or the whole of the extensor digitorum brevis muscle is used as a fascial or myofascial flap supplied by the dorsalis pedis artery and covered by a split-thickness skin graft. The purpose is to decrease the morbidity of the donor site, which is closed by direct sutures without skin grafting. Four cases are reported with minimal donor-site morbidity and full survival of the flaps. The mean follow-up period is 17 months.     

20-Hydroxyecdysone mediated activation of larval haemolymph protein uptake by fat body cells of Corcyra cephalonica (Insecta)

Evidence is presented here to show that 20-hydroxyecdysone is essential for the activation of the larval fat body for differential uptake of larval haemolymph proteins (LHPs). By using radiolabelled LHPs it is shown that the fat body cells of Corcyra cephalonica selectively incorporate LHPs during late-larval and prepupal development. Fluorographic analysis of the labelled fat body proteins from prepupal stage separated on sodium dodecyl-sulphate polyacrylamide gels suggests that the LHPs are sequestered without any degradation. Although, during the last larval instar the uptake of all the three LHPs (LHP 1, LHP 2 and LHP 3) by the fat body cells is very low, 20-hydroxyecdysone treatment of early, mid or late-last instars causes a significant increase in uptake of all the three LHPs. However, the response to hormone treatment was more pronounced in late-last instar when compared to early and mid-last instar.     

Factors affecting ureolytic activities ofPenicillium waksmanii isolated from sewage sludge

Twenty one fungal isolates belonging to 7 genera were screened for ureolytic activity. APenicillium waksmanii isolate was found to be the most potent and was selected for further study. No ammonia-nitrogen was detected inP. waksmanii cultures either urea-free or containing up to 1 g urea per L. The maximum extracellular urease production was recorded at a urea concentration of 15 g/L. It peaked after 6 d of incubation at 25°C when the initial pH of the glucose—peptone broth was adjusted to 6. On the other hand, the highest fungus biomass was detected at a concentration of 2 g urea per L after 4 d of incubation at 35°C when the pH of the medium was 8. The intracellular urease activity (measured in cell-free extract) was the highest at 12 mg urea per mL after 75-min incubation at 25°C at pH 8. Incubation temperature of 25°C favored both urease production and activity.     

The Potential Efficacy of Glycyrrhizic Acid and Its Nanostructure Against Brown Rot of Peach fruits

Production of peaches (Prunus persica (L.) Batsch) for both local market and export is increasing each year in Egypt. Brown rot disease, caused by Monilinia laxa and Monilinia fructigena, is considered one of the most important postharvest rots affecting peaches in Egypt and economic losses are increasing. Antifungal activity of glycyrrhizic acid nanoparticles (GA-NPs) and glycyrrhizic acid (GA) at 0.2 and 0.4 mmol/L was investigated as a control for both these brown rot pathogens on peach fruits in both in vitro and in vivo studies. In the in vitro studies, GA-NPs were the most effective as shown by the ability to decrease linear growth of both brown rot pathogens in potato dextrose agar (PDA) amended with 0.4 mmol/L GA-NPs. Micrographs of M. fructigena exposed to 0.4 mmol/LGA showed mycelial deformations, nodule formation, detachment of the cell wall, shrinkage and inhomogeneous cytoplasmic materials with large vacuoles. Mycelium of M. laxa exposed to 0.4 mmol/ LGA-NPs resulted in thinner and distorted hyphae, nodule formation, cell wall thinning, and swellings. The GANPs and GA treatments improved fruit quality by maintaining firmness and total soluble solids (TSS). GA-NPs were more effective in decreasing decay incidence than their bulk material. The 0.4 mmol/L GA-NPs completely inhibited the disease on naturally infected peach fruits for both seasons of 2018 and 2019. Furthermore, 0.4 mmol/L GA-NPs reduced the disease incidence in inoculated fruits by 95 (M. laxa) and 88% (M. fructigena) in 2018 season and 96 (M. laxa) and 85% (M. fructigena) in 2019 season. In conclusion, GA-NPs could enhance the resistance of peaches against brown rot caused by M. laxa and M. fructigena.     

Therapeutic Potential of Clove Essential Oil in Diabetes: Modulation of Pro-Inflammatory Mediators,Oxidative Stress and Metabolic Enzyme Activities

Type 1 diabetes is characterized by insulin deficiency due to the destruction of pancreatic β cells, leading to hyperglycemia, which in turn induces vascular complications. In the current study, we investigated the effect of intraperitoneal administration of clove essential oil (CEO: 20 mg/kg body weight) on certain oxidative stress and glucose metabolism enzymes, as well as the expression of proinflammatory mediators. Administration of CEO to diabetic rats showed a significant decline in blood glucose levels, total cholesterol, and xanthine oxidase, compared to the streptozotocin group. Furthermore, these treated rats elicited a notable attenuation in the levels of lipid peroxides, and thiols groups in both liver and brain tissues. The activities of antioxidant and metabolic enzymes were reverted to normality in diabetic upon CEO administration. In addition to its protective effects on red blood cell hemolysis, CEO is a potent α-amylase inhibitor with an IC₅₀=298.0±2.75 μg/mL. Also, treatment of diabetic rats with CEO significantly reduced the iNOS expression in the spleen. Our data showed that CEO has potential beneficial effects on diabetes, which can possibly prevent the pathogenesis of diabetic micro- and macrovascular complications.     

Synthesis,Biological Evaluation,and Molecular Modeling Studies of New 1,3,4-Thiadiazole Derivatives as Potent Antimicrobial Agents

In this work, the synthesis, characterization, and biological activities of a new series of 1,3,4-thiadiazole derivatives were investigated. The structures of final compounds were identified using ¹H-NMR, ¹³C-NMR, elemental analysis, and HRMS. All the new synthesized compounds were then screened for their antimicrobial activity against four types of pathogenic bacteria and one fungal strain, by application of the MIC assays, using Ampicilin, Gentamycin, Vancomycin, and Fluconazole as standards. Among the compounds, the MIC values of 4 and 8 μg/mL of the compounds 3f and 3g , respectively, are remarkable and indicate that these compounds are good candidates for antifungal activity. The docking experiments were used to identify the binding forms of produced ligands with sterol 14-demethylase to acquire insight into relevant proteins. The MD performed about 100 ns simulations to validate selected compounds’ theoretical studies. Finally, using density functional theory (DFT) to predict reactivity, the chemical characteristics and quantum factors of synthesized compounds were computed. These results were then correlated with the experimental data. Furthermore, computational estimation was performed to predict the ADME properties of the most active compound 3f .     

Propolis Enhances 5-Fluorouracil Mediated Antitumor Efficacy and Reduces Side Effects in Colorectal Cancer: An in Vitro and in Vivo Study

In this study, we investigated the combined treatment of 5-fluorouracil (5-FU) and Anatolian propolis extract (PE) on colorectal cancer (CRC)using in vitro and in vivo studies. We exposed luciferase-transfected (Lovo-Luc CRC) cells and healthy colon cells (CCD-18Co) to varying concentrations of 5-FU and PE to assess their genotoxic, apoptotic, and cytotoxic effects, as well as their intracellular reactive oxygen species (iROS) levels. We also developed a xenograft model in nude mice and evaluated the anti-tumor effects of PE and 5-FU using various methods. Our findings showed that the combination of PE and 5-FU had selectivity against cancer cells, particularly at higher doses, and enhanced the anti-tumor effectiveness of 5-FU against colon CRC. The results suggest that PE can reduce side effects and increase the effectiveness of 5-FU through iROS generation in a dose-dependent manner.     

Facile Synthesis of Hybrid Nanoflowers Using Glycine and Phenylalanine and Investigation of Their Catalytic Activity

In the context of the proposed work, two different amino acids (Glycine, Phenylalanine) have interacted with copper ions in a phosphate buffer (PBS) in place of enzymes. This interaction resulted in the nucleation of copper phosphate crystals and the formation of flower-shaped amino acid-copper hybrid nanostructures (AA-hNFs), which grew through self-assembly. While Cu (II) ions in the structure of AA-hNFs were used as Fenton's agent for the catalytic activity. SEM, energy dispersive X-ray spectroscopy, X-ray diffraction, and Fourier transform infrared spectroscopy measurements were used to define the AA-hNFs′ characterisation. The peroxidase-like activities of AA-hNFs were investigated by UV/VIS spectrophotometer. Metal nanoparticles have peroxidase-like activity. A class of enzymes known as peroxidases is able to catalyze the conversion of hydrogen peroxide into hydroxyl radicals. These radicals also take part in electron transfers with substrates, which results in color during oxidation. When cupric oxide nanoparticles are added to the peroxidase substrate while H₂O₂ is present, a blue color product with a maximum absorbance at=652 nm can result, demonstrating the catalytic activity of a peroxidase. The morphology and composition of AA-hNFs were carefully characterized and the synthesized parameters were optimized systematically. Results showed that the nanoparticles were dispersed with an average diameter of 7–9 μm and indicated a uniform flower shape. The results of the investigation are anticipated to significantly advance a number of technical and scientific sectors.     

Maturational changes in responses of tissue and airway resistance to histamine

Dreshaj, Ismail A., Musa A. Haxhiu, Charles F. Potter, FatonH. Agani, and Richard J. Martin. Maturational changes in responsesof tissue and airway resistance to histamine. J. Appl.Physiol. 81(4): 1785-1791, 1996.We determinedhow postnatal maturation affects the relative contributions of airwaysand lung parenchyma to pulmonary resistance(RL) and whether there are developmental differences in their respective responses to constrictive agents. We studied open-chest ventilated anesthetized piglets of threeages: 2-4 days, 2-3 wk, and 10 wk.RL was partitioned into tissue(Rti) and airway (Raw) resistance by means of alveolar capsules underbaseline conditions and after intravenous histamine. Postnatalmaturation was associated with a progressive decline inRL, Rti, and Raw and with anincrease in the contribution of Rti toRL from 38 ± 8% at 2-4days to 72 ± 2% at both 2-3 and 10 wk. Histamine causedRL to increase at all ages. Whenpartitioned into Rti and Raw, the percent increase in Rti significantlyexceeded that of Raw at both 2-4 days and 2-3 wk. Incontrast, the percent increase in Raw significantly exceeded that ofRti at 10 wk. Administration of atropine before histamine in pigletsaged 10 wk reduced the response of Rti and Raw to histamine.Histamine-induced responses ofRL were blocked by priorH₁-receptor blockade withpyrilamine (2 mg/kg). These results indicate that1) the contribution of Rti and Rawto RL changes during maturationand that 2) contractile responses toexogenous histamine are manifest predominantly in most distal airwaysand lung parenchyma during early postnatal life; with advancingmaturation there is greater contribution of airways to the increase inRL induced by histamine.