Publications

Abstract Quercetin is evidently unstable in Dulbecco's modified Eagle's medium (DMEM) at 37°C. However, the underlying mechanism of this instability is not clear yet. The stability and new degradation products of quercetin in DMEM at 37°C were investigated via in UPLC‐MS‐MS analysis. With increasing incubation time, quercetin formed various degradation products derived from its dimer and there were numerous isomers formed during this process. Ascorbic acid significantly improved the stability of quercetin by protecting quercetin from auto‐oxidation in this medium. Ascorbic acid also remarkably enhanced the stability of quercetin in DMEM in the presence of A549 cells and obviously increased the antiproliferative effect of quercetin toward A549 cells.

The genus Pyrus, which includes pear species, comprises approximately 22 species and 5,000 subspecies. Pears are commercially important due to their environmental adaptability and are widely distributed across North Africa, Europe, and Asia. Pyrus species are rich in phytochemicals known for their anticancer, antiviral, and antioxidant properties. This study investigates the chemical composition and biological activity of leaf, stem, and fruit extracts of Pyrus calleryana growing in Egypt, using UPLC-MS/MS and GNPS molecular networking, and assessing antioxidant and enzyme inhibitory activities. A total of 73 compounds were identified, the majority of which were phenolic compounds. These included benzoic and cinnamic acid derivatives, flavonoids, triterpenoids, fatty acids, phospholipids, glycolipids and sugars. The stem extract exhibited significant in vitro antioxidant and enzyme inhibitory activity. Antioxidant activity of stems extract was assessed (in comparison to other organs) in several antioxidant assays, e.g. DPPH (367.06 ± 4.65 mg TE/g), ABTS (392.8 ± 7.04 mg TE/g), FRAP (206.73 ± 5.12 mg TE/g), phosphomolybdenum (1.89 ± 0.05 mmol TE/g), and others. Furthermore, the P. calleryana leaf extract inhibited MDA-MB-231 cell viability in a concentration-dependent manner after 48 h. These results highlight the promising potential of Pyrus calleryana as a rich source of bioactive compounds with antioxidant, enzyme inhibitory, and cytotoxic activities, supporting its further exploration in pharmaceutical and nutraceutical applications.

Abstract Introduction The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a recent outbreak of Coronavirus Disease (COVID-19). In Cuba, the first case of COVID-19 was reported on March 11. Elderly with multiple comorbidities are particularly susceptible to adverse clinical outcomes in the course of SARS CoV-2 infection. During the outbreak, a local transmission event took place in a nursing home in Villa Clara province, Cuba, in which nineteen elderly residents were positive for SARS-CoV-2. Methods Based on the increased susceptibility to viral-induced cytokine release syndrome inducing respiratory and systemic complications in this population, the patients were included in an expanded access clinical trial to receive itolizumab, an anti-CD6 monoclonal antibody. Results All the patients had underlying medical conditions. The product was well tolerated. After the first dose, the course of the disease was favorable and 18 out of 19 (94.7%) patients were discharged clinically recovered with negative RT-PCR at 13 days (median). One dose of itolizumab, circulating IL-6 decreased in the first 24-48 hours in patients with high baseline values, whereas in patients with low levels, this concentration remained over low values. To preliminary assess the effect of itolizumab, a control group was selected among the Cuban COVID-19 patients, which did not receive immunomodulatory therapy. Control subjects were well-matched regarding age, comorbidities and severity of the disease. Every three moderately ill patients treated with itolizumab, one admission in intensive care unit (ICU) was prevented. Discussion/Conclusion Itolizumab was well tolerated. Its effect is associated with a reduction and controlling IL-6 serum levels. Moreover, treated patients had a favorable clinical outcome, considering their poor prognosis. This treatment is associated significantly with a decrease the risk to be admitted in ICU and reduced 10 times the risk of death. This study corroborates that the timely use of itolizumab, in combination with other antiviral and anticoagulant therapies, is associated with a reduction the COVID-19 disease worsening and mortality. The humanized antibody itolizumab emerges as a therapeutic alternative for patients with COVID-19 and suggests its possible use in patients with cytokine release syndrome from other pathologies.

Dihydromyricetin (DHM) dramatically improved the quality of life for Streptozotocin (STZ)‐induced diabetic rats and significantly increased the activity of antioxidant enzymes in the liver. Moreover, DHM successfully ameliorated diabetes‐induced liver damage by suppression of apoptosis in the liver, as indicated by the decreased levels of Bax and cleaved caspase‐3. In diabetic rats, the levels of tumor necrosis factor‐ α and interleukin‐1 β in the liver were significantly increased. However, the administration of DHM (100–400 mg/kg/day) for 6 weeks restored the cytokine levels to their normal values in a dose‐dependent manner in diabetic rats by the regulation of nuclear factor‐kappa B signaling pathway. In addition, DHM significantly induced 5′ AMP‐activated protein kinase (AMPK) phosphorylation and decreased MyD88, TLR4, p38, GSK‐3 β protein expression levels in the liver of diabetic rats. In conclusion, DHM could improve STZ‐induced liver impairment by preventing oxidative stress, apoptosis, and inflammation.

Abstract Lectin‐glycan interactions sustain fundamental biological processes involved in development and disease. Owing to their unique sugar‐binding properties, lectins have great potential in glycobiology and biomedicine. However, their relatively low affinities and broad specificities pose a significant challenge when used as analytical reagents. New approaches for expression and engineering of lectins are in demand to overcome current limitations. Herein, we report the application of bacterial display for the expression of human galectin‐3 and mannose‐binding lectin in Escherichia coli . The analysis of the cell surface expression and binding activity of the surface‐displayed lectins, including point and deletion mutants, in combination with molecular dynamics simulation, demonstrate the robustness and suitability of this approach. Furthermore, the display of functional mannose‐binding lectin in the bacterial surface proved the feasibility of this method for disulfide bond‐containing lectins. This work establishes for the first time bacterial display as an efficient means for the expression and engineering of human lectins, thereby increasing the available toolbox for glycobiology research.

Olives from Picual, Arbequina, Manzanilla de Sevilla, and Local cultivars together with their corresponding oils were analyzed in terms of odor activity values (OAVs) to establish the relationship between the aromatic profile of both olives and oils. The OAVs for the different compounds were classified in nine odorant series: grass, leaf, wood, bitter, sweet, pungent, olive fruit, apple, and banana. The total intensities for every aromatic series were calculated as the sum of the OAVs of each compound associated with this series. As a result, olives had characteristic profiles. Picual cultivar had not a clear sensory characterization from the volatile compounds. Arbequina cultivar was mainly characterized by apple and bitter odorant series; Manzanilla de Sevilla by apple, bitter, and grass odorant series; and Local variety by banana and olive fruit. However, in the oils obtained from those olives, these differences disappeared, and all oils showed the same profile with pungent, bitter, and wood odorant series most strongly contributing.

The effect of fungicides on fermentation is of paramount importance to control the quality and safety of wines. In this work, the quality (enological parameters, color, phenolic content, antioxidant activity, and fungicide residues) of wines from Monastrell grapes fortified with iprovalicarb, mepanipyrim, and tetraconazole fungicides was evaluated. Along the winemaking process, initial residues of mepanipyrim and tetraconazole were removed in more than 90% while the dissipation of iprovalicarb was around 73%. Significant statistical differences were found in the presence of iprovalicarb and mepanipyrim residues, especially at the highest concentration assayed. For both fungicides, increases in the volatile acidity (between 4 and 8.6 times), the lactic acid content (between 8.6 and 20.5 times), the percentage of polymeric anthocyanins (between 1.3 and 1.7 times), and also a slight increase of the total phenolic index and the total anthocyanin content determined by spectrophotometry were observed. On the contrary, the total monomeric anthocyanins content decreased about 16.3% and 28.6% in the presence of iprovalicarb and mepanipyrim, respectively. These results could be related to a higher development of acetic acid or lactic bacteria in the presence of these fungicides. The color of the final wines was also different in comparison with the control, with a higher yellow component, color intensity, tonality, and hue angle because of pH changes in the medium. Tetraconazole fermentations had a more similar trend to the control wine, probably due to the lower concentration of this fungicide in the grape must at the initial time. No effects on the antioxidant activity was observed for any of the target fungicides. A multivariate statistical analysis was done to view the interrelationships between different variables (color and anthocyanins profile). The obtained model allowed the wines to be separated according to the fungicide treatment applied.

Abstract Major objectives of this work were to: (1) substantiate the 24‐hour pattern in the occurrence of childhood febrile seizures (CFSs) by a novel time series meta‐analysis of past reported time‐of‐day data and (2) discuss its potential circadian rhythm‐dependencies. Comprehensive search of the published literature retrieved eight articles that met inclusion criteria. Three investigations were conducted in Iran, two in Japan, and one each in Finland, Italy, and South Korea, representing a total of 2461 mostly simple febrile seizures of children who were on average about 2 years of age. Population‐mean cosinor analysis validated ( p < .001) a 24‐hour pattern in the onset of CFSs, with an approximate four‐fold difference in the proportion of children expressing seizures at its peak at 18:04 h (95% confidence interval: 16:40–19:07 h) vs trough at 06:00 h, in the absence of meaningful time‐of‐day differences in mean body temeprarure. The CFS time‐of‐day pattern likely derives from the actions of multiple circadian rhythms, particularly the cytokines that comprise the pyrogenic inflammatory pathway and melatonin that influences the excitation level of central neurons and helps regulate body temperature. Past laboratory animal and patient investigations document that the vulnerability to a seizure by a provoking trigger of the same intensity is not the same but different in a predictable‐in‐time manner during the 24 h as a circadian susceptibility/resistance rhythm. Knowledge of the marked disparity in the time‐of‐day risk of CFSs can be translated into improved prevention, particularly during the late afternoon and early evening when highest, through proper timing of prophylactic interventions.