Novel hit of DPP-4Is as promising antihyperglycemic agents with dual antioxidant/anti-inflammatory effects for type 2 diabetes with/without COVID-19.

DPP-4Is are well recognized therapy for type 2 diabetes. In spite of sharing a common mode of action, the chemical diversity among members of DPP-4Is raised the question whether structural differences may result in distinguished activities. DPP-4Is were recently explored as drug repurposing means for treatment of SARS-CoV-2 due to the urgent need for small molecule drugs for controlling infections. The use of DPP-4Is was not correlated with adverse COVID-19-related consequences among patients with type 2 diabetes. Inspired by these reasons and the importance of pyrimidinone ring as DPP-4I with both antioxidant and anti-inflammatory activities, we succeeded to prepare some novel pyrimidinone and thio-pyrimidinone derivatives, which were then screened for their antidiabetic activity and DPP-4 inhibition. In addition, their anti-inflammatory effect on LPS-stimulated RAW 264.7 cells were evaluated. Furthermore, their antioxidant activities were also tested.

Antioxidant Property of the Egyptian Propolis Extract Versus Aluminum Silicate Intoxication on a Rat's Lung: Histopathological Studies.

In this study, we evaluated the inflammatory responses induced by aluminum silicate (AS) cytotoxicity in rat lungs. The prophylactic effect of propolis extract was evaluated in 60 adult male albino rats. The rats were divided into six groups: (1) a normal, healthy control group; (2) a normal group fed with 200 mL of propolis extract/Kg; (3) a low-dose positive control group injected with 5 mg/kg of AS; (4) a treated group given propolis and a low dose of AS; (5) a high-dose positive control group injected with 20 mg/kg of AS; and (6) a treated group given propolis with a high-dose of AS. At the end of the two-month experiment, the rats' lungs were removed. For each pair of lungs, one portion was subjected to biochemical analysis and the other underwent hematoxylin and eosin (H&E) staining in order to study its histology. The rats that received AS doses displayed significant disorders in their antioxidant contents as well as in their enzymatic activities and their histopathological structures revealed severe damage to their lung tissues. Upon the rats being treated with propolis, the enzymatic and antioxidant contents improved and partial improvements in the lung structures appeared, including minimized congestion, a reduced hemorrhage of blood vessels and preserved bronchioles, alveolar ducts, and alveoli. The prophylactic effectiveness of propolis extract on the cytotoxicity of AS, owing to the antioxidant properties of propolis, were studied.

Tuning the viscoelasticity of nonionic wormlike micelles with ß-cyclodextrin derivatives: a highly discriminative process.

We report the influence of five ß-cyclodextrin (ß-CD) derivatives, namely: randomly methylated ß-cyclodextrin (MBCD), heptakis (2,6-di-O-methyl)-ß-cyclodextrin (DIMEB), heptakis (2,3,6-tri-O-methyl)-ß-cyclodextrin (TRIMEB), 2-hydroxyethyl-ß-cyclodextrin (HEBCD) and 2-hydroxypropyl-ß-cyclodextrin (HPBCD), on the self-assembly of mixtures of nonionic surfactants: polyoxyethylene cholesteryl ether (ChEO10) and monocaprylin (MCL). Mixtures of ChEO10/MCL in water form highly viscoelastic wormlike micelle solutions (WLM) over a range of concentrations; herein, the composition was fixed at 10 wt % ChEO10/3 wt % MCL. The addition of methylated ß-CDs (MBCD, DIMEB, TRIMEB) induced a substantial disruption of the solid-like viscoelastic behavior, as shown from a loss of the Maxwell behavior, a large reduction in G' and G″ in oscillatory frequency-sweep measurements, and a drop of the viscosity. The disruption increased with the degree of substitution, following: MBCD < DIMEB < TRIMEB. Cryo-TEM images confirmed a loss of the WLM networks, revealing short rods and disc-like aggregates, which were corroborated by small-angle neutron scattering (SANS) measurements. Critical aggregation concentrations (CAC), measured by fluorescence spectroscopy, increased in the presence of DIMEB for both ChEO10 and MCL, suggesting the existence of interactions between methylated ß-CDs and both surfactants involved in WLM formation. Instead, hydroxyl-ß-CDs had a very different effect on the WLM. HPBCD only slightly reduced the solid-like behavior, without suppressing it. Quite remarkably, the addition of HEBCD reinforced the solid-like characteristics and increased the viscosity 10-fold. Cryo-TEM images confirmed the subsistence of WLM in ChEO10/MCL/HEBCD solutions, while SANS data revealed a slight elongation and thickening of the worms, and an increase of associated water molecules. CAC data showed that HPBCD had little effect on either surfactant, while HEBCD strongly affected the CAC of MCL and only slightly affected the ChEO10. For both DIMEB and HEBCD, time-resolved SANS measurements showed that morphology changes underlying these macroscopic changes occur in less than 100 ms.

Biodeterioration effects of three Aspergillus species on stucco supported on a wooden panel modeled from Sultan al-Ashraf Qaytbay Mausoleum, Egypt.

This study focuses on the magnificent decoration of a painted and gilded wooden panel with signs of fungal biodeterioration caused by Aspergillus species in the Mausoleum of Sultan al-Ashraf Qaytbay, Cairo, Egypt. Numerous spectroscopic analyses and investigation techniques, including Scanning Electron Microscope Equipped with Energy Dispersive X-ray analysis (SEM-EDX), Fourier Transform Infrared analysis (FTIR), and X-Ray Diffraction (XRD) have been used to study the materials that comprise this painted and gilded wooden panel composition. Aspergillus niger, A. flavus, and A. terreus were recognized as isolated fungi, and their accession numbers are OQ820164, OQ820163, and OQ820160, respectively. The findings showed that the wooden support is of pinewood (Pinus halepensis), the white priming layer on top of the wooden support was identified as gypsum, the blue paint layer has been proposed to be Azurite, Au (gold) was the primary composition of the gilding layer, while Pb (lead) was detected in some spots, suggesting the use an alloy of gold with lead, and finally, animal glue was the bonding medium. Based on these findings, mimic samples with identical substrates and structural components have been designed, and the biodeterioration signs by the growing of the three Aspergillus species-A. niger, A. flavus and A. terreus were evaluated via SEM and color change. However, A. niger was discovered with density growth on surfaces of pinewood, gypsum, and Azurite and with less growth on the gilding layer after 6-month incubation. This contrasts with A. terreus and A. flavus, which had greater density growth on Azurite and stucco than on pinewood and less growth on the gilding layer. The used analytical methods with detailed analyses revealed the novelty and significant future aspects of the conservation of the painted and gilded wooden panel. Particularly given that this location is used for prayer and is crowded with people five times a day, which increases the accumulation of fungi and negatively affects both the historic Mosque and the worshippers' health.

Comparative Study between First and Second Harmonics of a Nd:YAG Laser for Cleaning Manifestation Damages That Appeared in Pigments Used on Archaeological Cartonnage.

This study focused on identifying the effect of the laser wavelengths used in cleaning some manifestation damage appearing in pigments used on archaeological cartonnage preserved in the Egyptian Museum, Egypt. The manifestations of damage appear as mud, resin, color, dust and microbiological damage stains. Lasers were chosen as one of the modern applications that give good results when cleaning the pigment materials without making direct contact with the material. Accordingly, lasers with a wavelength of 532 and 1064 nm were tested to identify their effect on stains caused by pigments and to choose the best one for use in cases similar to those materials in the future. This study was conducted to identify the effect of the selected wavelengths and choose the best ones to apply to the archaeological model. The evaluations were conducted using several tests and analyses, such as digital microscopy, X-ray florescence, Fourier transform infrared spectroscopy, and Handy colorimetry to evaluate that effect of lasers with a wavelength of 532 and 1064 nm to remove stains. The experimental study demonstrated the good effect of the Nd:YAG laser with a wavelength of 1064 nm compared with that of the 532 nm laser. The results of using the Nd:YAG laser proved the good effect of removing all stains compared with the 532 nm laser, which caused big changes when used to clean the stains on the pigment's surfaces; it also did not help in removing or reducing some stains such as mud stains. According to these results, the good effect of the Nd:YAG laser (1064 nm) make it more suitable for cleaning than that of the Nd:YAG laser (532 nm), which is not recommended for use as it gave bad results when applied.

Clinical Consequences for Individuals Treated with Tocilizumab for Serious COVID-19 Infection.

There seem to currently be no therapeutic medications found for the severe coronavirus infection in 2019 (COVID-19). In light of this, it has been hypothesized that the immunomodulatory treatment known as tocilizumab can lessen the inflammatory response that occurs in the respiratory system, speed up the process of clinical benefit, lower the risk of death, and avert the need for ventilators. This randomized controlled trial (RCT) studied patients with a proven infection of SARS-CoV-2 and hyperinflammatory reactions. The inclusion criteria included fever (body temperature > 38 °C), pulmonary infiltrates, or supplemental oxygen. The patients received either conventional treatment with one dose of either tocilizumab (8 mg per kilogram of body weight) or conventional treatment only. The subjects were randomized to receive either treatment with a 1:1 ratio. A time-to-event test was conducted to determine the time to intubation or death. There was an insignificant difference between the investigated groups regarding the time to death, time to mechanical ventilation, and percentage of deaths. The conventional group's median (IQR) hospital length of stay was 4 (3-6) days, whereas the tocilizumab therapy group was 7 (4.75-10) days. There was a substantial difference in the mechanical ventilation rates in both groups, which were 17 (34%) and 28 (56%), respectively. In hospitalized patients with severe illness and COVID-19, tocilizumab was ineffective in preventing intubation or death. Trials must be larger, however, in order to exclude the potential benefits or harms.

Parents' Perception, Acceptance, and Hesitancy to Vaccinate Their Children against COVID-19: Results from a National Study in the UAE.

Introduction: COVID-19 is considered the greatest health disaster affecting humans during the 21st century, which urged the need to develop an effective vaccine to acquire enough immunity against the virus. The main challenge faced during the development of such vaccines was the insufficiency of time, which raised the question about the vaccine safety and efficacy, especially among children. Parents' and caregivers' thoughts and acceptance of administering the vaccine to their children are still debatable topics and are yet to be explored in the UAE. Aims: The study aims to exploit parent acceptance, perception, and hesitancy toward the COVID-19 vaccine administration for their children and the link with their choice of distance learning instead of face-to-face education in the UAE. Methodology: This study utilized a cross-sectional descriptive design. A sample of 1049 parents across all emirates were conveniently approached and surveyed using Google forms from June to September 2021. The participants responded to a semi-structured questionnaire pertaining to socio-demographic, educational, and other questions related to COVID-19 and its link with their beliefs in whether the vaccination of their children will help with resuming face-to-face learning. Results: Approximately 74% of the parents confirmed that their children who are 16 years old and above have received the vaccine, and 71% were willing to give the vaccine to their children aged above 5 years. Parents with children receiving online education and those with children where the online modality of learning negatively affected their academic achievement are more prone to administer the COVID-19 vaccine to their children above five years old. The results show a significant association between vaccination of children and the parental desire for resuming physical attendance in schools (p value < 0.001). Multivariate analysis showed that the highest acceptance rate was from parents with children of low academic achievement due to online learning modality during the pandemic. Conclusion: In the UAE, parents of young children have shown a positive attitude towards COVID-19 vaccination in belief that vaccines will reduce the risk of infection and assist in resuming normal lifestyles, such as going back physically to schools. The results reflect the public awareness and the hypervigilance regarding the COVID-19 pandemic in the UAE.

Solubilization of oils or addition of monoglycerides drives the formation of wormlike micelles with an elliptical cross-section in cholesterol-based surfactants: a study by rheology, SANS, and cryo-TEM.

We report the formation of wormlike micelles (WLM) in poly(oxyethylene) cholesteryl ether (ChEO(10)) aqueous solutions by the addition of lipophilic monoglycerides at room temperature (monolaurin (ML), monocaprin (MC), and monocaprylin (MCL)) bearing 12-, 10-, and 8-carbon alkyl chains, respectively. A combination of rheology, small-angle neutron scattering (SANS), and cryo-TEM was used to study their viscoelastic properties and structure. With the successive addition of cosurfactant, a significant increase in viscosity and a clear solidlike behavior is obtained, suggesting the formation of a viscoelastic network of wormlike micelles. Only for MCL is typical Maxwellian behavior obtained. The onset of micellar growth, as detected by the occurrence of solidlike behavior and a significant increase in viscosity, is obtained for 0.30 (1 wt%), 0.34 (1 wt%), and 0.60 (1.5 wt%) cosurfactant/ChEO(10) molar ratios with ML, MC, and MCL, respectively. With ML and MC, extremely long relaxation times (exceeding 20 s) compared to those of MCL are obtained, and zero-shear viscosity values are more than 1 order of magnitude higher than with MCL. These results show that cosurfactants with longer alkyl chain lengths (ML and MC) induce the formation of longer wormlike micelles and do so at lower concentrations. SANS measurements on dilute solutions confirm that the viscoelastic behavior correlates with an increase in contour length and reveals an elliptical cross-section with an axial ratio of around 2. Cryo-TEM images provide visual evidence of the wormlike micelles and confirm the elliptical shape of the cross-section. The addition of small amounts of aliphatic oils (ethyl butyrate, EB, and ethyl caprylate, EC) and cyclic oils (peppermint, PP, and tea tree, TT, oils) to ChEO(10) solutions induces wormlike micelle formation at a lower cosurfactant concentration or even in its absence (for PP, TT, and EC) because of their probable localization in the palisade layer. The viscosity peak and height of the plateau modulus occur at increasing monoglyceride concentration following the order PP ≈ TT > EC > EB > no oil.

Structural transitions in cholesterol-based wormlike micelles induced by encapsulating alkyl ester oils with varying architecture.

The effect of encapsulating oils on the phase behaviour and the microstructure of wormlike micelles formed by polyoxyethylene cholesteryl ether (ChEO(10)) and triethylene glycol monododecyl ether co-surfactant (C(12)EO(3)) was investigated using rheology, Cryo-TEM and small-angle neutron scattering measurements. Six alkyl ester oils bearing small, systematic variations in their molecular structure were encapsulated: ethyl butyrate (EB(24)), ethyl caproate (ECO(26)), ethyl caprylate (EC(28)), methyl enanthate (ME(17)), methyl caprylate (MC(18)) and butyl butyrate (BB(44)), where the subscripts refer to the length of the alkyl chain and fatty acid chain, respectively, on either sides of the ester link. The addition of alkyl ester oils to ChEO(10)/C(12)EO(3) solutions promotes the longitudinal growth of the surfactant aggregates into wormlike micelles possessing an elliptical cross-section, with r(minor) 31±2 Å and r(major) varying from 45 to 70 Å. At fixed alkyl chain length, oils with longer fatty acid chains were found to be more efficient in inducing wormlike micelle formation or their elongation, following the order: EC(28)>ECO(26)>EB(24). Instead, at fixed fatty acid chain length, increasing the alkyl chain has a negative effect on the longitudinal micellar growth (MC(18)>EC(28) and EB(24)>BB(44)). At high co-surfactant concentrations and in the presence of EB(24), an unusual phase of ring-like micelles was detected. Overall, the orientation of the oil molecules within the micelles enables them to act as co-surfactants with a small head-group, decreasing the average cross-section area and promoting longitudinal growth of the micelles into worms.

Plasma adrenomedullin level in Egyptian children and adolescents with type 1 diabetes mellitus: relationship to microvascular complications.

BACKGROUND: Adrenomedullin (AM) is known to be elevated in different clinical situations including diabetes mellitus (DM), but its potential role in the pathogenesis of vascular complications in diabetic children and adolescents is to be clarified. Hence, the study aimed at assessment of plasma adrenomedullin levels in children and adolescents with type 1 DM and correlation of these levels with metabolic control and diabetic microvascular complications (MVC). METHODS: The study was performed in the Diabetes Specialized Clinic, Children's Hospital of Ain Shams University in Cairo, Egypt. It included 55 diabetic children and adolescents (mean age 13.93 +/- 3.15 years) who were subdivided into 40 with no MVC and 15 with MVC. Thirty healthy subjects, age-and sex-matched, were included as control group (mean age 12.83 +/- 2.82 years). Patients and controls were assessed for glycosylated hemoglobin (HbA1c) and plasma adrenomedullin assay using ELISA technique. RESULTS: Mean plasma AM levels were significantly increased in patients with and without MVC compared to control group, (110.6 pg/mL, 60.25 pg/mL and 39.2 pg/mL respectively) (P < 0.01) with higher levels in those with MVC (P < 0.05). Plasma AM levels were positively correlated with both duration of diabetes (rho = 0.703, P < 0.001) and glycemic control (HbA1c) (rho = 0.453, P < 0.001). CONCLUSION: Higher plasma AM levels in diabetics particularly in those with MVC & its correlation with diabetes duration and metabolic control may reflect the role of AM in diabetic vasculopathy in the pediatric age group.