Improvement and enhancement of oligosaccharide production from Lactobacillus acidophilus using statistical experimental designs and its inhibitory effect on colon cancer.

Colorectal cancer (CRC) is the third cause of death by cancers worldwide and is one of the most common cancer types reported in both Egypt and the United States. The use of probiotics as a dietary therapy is increasing either as a prevention or as a treatment for many diseases, particularly, in the case of CRC. The increasing acceptance of lactic acid bacterial (LAB) oligosaccharides as bioactive agents has led to an increase in the demand for the large-scale production of LAB-oligosaccharides using fermentation technology. Therefore, in the current study, we are using the Plackett- Burman design (PBD) approach, where sixteen experimental trials were applied to optimize the production of the target oligosaccharide LA-EPS-20079 from Lactobacillus acidophilus. Glucose, yeast extract and sodium acetate trihydrate were the top three significant variables influencing LA-EPS production. The maximum concentration of LA-EPS-20079 achieved by L. acidophilus was 526.79 µg/ml. Furthermore, Box-Behnken design (BBD) as response surface methodology (RSM) was used to complete the optimization procedure. The optimal levels of the chosen variables which were 30.0 g/l, glucose; 5 g/l, yeast extract and 10.0 g/l sodium acetate trihydrate with the predicted LA-EPS-20079 concentration of 794.82 µg/ml. Model validity reached 99.93% when the results were verified. Both optimized trials showed great cytotoxic effects against colon cancer line (CaCo-2) with inhibition percentages ranging from 64.6 to 81.9%. Moreover, downregulation in the expression level of BCL2 and Survivin genes was found with a fold change of 3.377 and 21.38, respectively. Finally, we concluded that the optimized LA-EPS-20079 has maintained its anticancer effect against the CaCo-2 cell line that was previously reported by our research group.

New apoptotic anti-triple-negative breast cancer theobromine derivative inhibiting EGFRWT and EGFRT790M: in silico and in vitro evaluation.

A new theobromine-derived EGFR inhibitor (2-(3,7-Dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)-N-(2,6-dimethylphenyl)acetamide) has been developed that has the essential structural characteristics to interact with EGFR's pocket. The designed compound is 2,6-di ortho methylphenyl)acetamide derivative of the well-known alkaloid, theobromine, (T-1-DOMPA). Firstly, deep DFT studies have been conducted to study the optimized chemical structure, molecular orbital and chemical reactivity analysis of T-1-DOMPA. Then, T-1-DOMPA's anticancer potentialities were estimated first through a structure-based computational approach. Utilizing molecular docking, molecular dynamics, MD, simulations over 100 ns, MM-PBSA and PLIP studies, T-1-DOMPA bonded to and inhibited the EGFR protein effectively. Subsequently, the ADMET profiles of T-1-DOMPA were computed before preparation, and its drug-likeness was anticipated. Therefore, T-1-DOMPA was prepared for the purposes of scrutinizing both the design and the results obtained in silico. The in vitro potential of T-1-DOMPA against triple-negative breast cancer cell lines, MDA- MB-231, was very promising with an IC50 value of1.8 µM, comparable to the reference drug (0.9 µM), and a much higher selectivity index of 2.6. Interestingly, T-1-DOMPA inhibited three other cancer cell lines (CaCO-2, HepG-2, and A549) with IC50 values of 1.98, 2.53, and 2.39 µM exhibiting selectivity index values of 2,4, 1.9, and 2, respectively. Additionally, T-1-DOMPA prevented effectively the MDA-MB-231cell line's healing and migration abilities. Also, T-1-DOMPA's abilities to induce apoptosis were confirmed by acridine orange/ethidium bromide (AO/EB) staining assay. Finally, T-1-DOMPA caused an up-regulation of the gene expression of the apoptotic gene, Caspase-3, in the treated MDA-MB-231cell.

Design and synthesis of thiazolidine-2,4-diones hybrids with 1,2-dihydroquinolones and 2-oxindoles as potential VEGFR-2 inhibitors: in-vitro anticancer evaluation and in-silico studies.

A thiazolidine-2,4-dione nucleus was molecularly hybridised with the effective antitumor moieties; 2-oxo-1,2-dihydroquinoline and 2-oxoindoline to obtain new hybrids with potential activity against VEGFR-2. The cytotoxic effects of the synthesised derivatives against Caco-2, HepG-2, and MDA-MB-231 cell lines were investigated. Compound 12a was found to be the most potent candidate against the investigated cell lines with IC50 values of 2, 10, and 40 µM, respectively. Furthermore, the synthesised derivatives were tested in vitro for their VEGFR-2 inhibitory activity showing strong inhibition. Moreover, an in vitro viability study against Vero non-cancerous cell line was investigated and the results reflected a high safety profile of all tested compounds. Compound 12a was further investigated for its apoptotic behaviour by assessing the gene expression of four genes (Bcl2, Bcl-xl, TGF, and Survivin). Molecular dynamic simulations authenticated the high affinity, accurate binding, and perfect dynamics of compound 12a against VEGFR-2.

New quinoline and isatin derivatives as apoptotic VEGFR-2 inhibitors: design, synthesis, anti-proliferative activity, docking, ADMET, toxicity, and MD simulation studies.

New quinoline and isatin derivatives having the main characteristics of VEGFR-2 inhibitors was synthesised. The antiproliferative effects of these compounds were estimated against A549, Caco-2, HepG2, and MDA-MB-231. Compounds 13 and 14 showed comparable activities with doxorubicin against the Caco-2 cells. These compounds strongly inhibited VEGFR-2 kinase activity. The cytotoxic activities were evaluated against Vero cells. Compound 7 showed the highest value of safety and selectivity. Cell migration assay displayed the ability of compound 7 to prevent healing and migration abilities in the cancer cells. Furthermore, compound 7 induced apoptosis in Caco-2 through the expressive down-regulation of the apoptotic genes, Bcl2, Bcl-xl, and Survivin, and the upregulation of the TGF gene. Molecular docking against VEGFR-2 emerged the interactions of the synthesised compounds in a similar way to sorafenib. Additionally, seven molecular dynamics simulations studies were applied and confirmed the stability of compound 13 in the active pocket of VEGFR-2 over 100 ns.

Effect of orange polarized light on post burn pediatric scar: a single blind randomized clinical trial.

[Purpose] This study was carried out to investigate the effect of orange filtered polarized polychromatic light on post burn pediatric scar. [Participants and Methods] Thirty children with post burn scar in wrist and hands participated in this study. They were between 3 to 7 years old, having hypertrophic burn scar ≥2 months post healing, free from concomitant skin disease and keloids. They were randomly assigned into two groups. The control group (A) (n=15) received Scar Standard Management (SSM) protocol and the study group (B) (n=15) received SSM protocol along with 15 min/area polarized light with medical range filter followed by 15 min/area orange filtered polarized light. All children received the study protocol once a day, 3 times/week for one month. Scar assessment was done before and after the study protocol by using Vancouver Scar Scale (VSS). [Results] All participated children were analyzed. Comparison of post treatment results between groups revealed significant improvement of post burn scar for both groups with significant difference in favor to the study group. [Conclusion] Ultimately it was revealed that Orange filtered polarized light has a special and beneficial effect on decreasing post burn pediatric scar.

A Preliminary Assessment of Global CO2: Spatial Patterns, Temporal Trends, and Policy Implications.

This study offers a comprehensive analysis of the distribution, evolution, and driving factors of CO2 emissions from 1990 to 2016 at multiple spatial scales. Utilizing 26 indicators encompassing various facets of CO2 emissions, it is employed principal component analysis (PCA) and empirical orthogonal functions (EOFs) to identify the dominant characteristics of global CO2 emissions. This model retained three core components, accounting for 93% of the global CO2 variation, reflecting emission trajectories and associated economic metrics, such as Gross domestic product (GDP). The analysis differentiated the effects of these components based on countries' economic standings. Using a novel aggregated index, significant national contributors to global CO2 emissions are pinpointed. Notably, the leading contributors are found among developed nations (e.g., the United States, Canada, Japan), Gulf states (e.g., Saudi Arabia, Qatar), and emerging economies (e.g., China, Brazil, Mexico). Furthermore, these results highlight that shifts in global CO2 emissions over the past 30 years are predominantly influenced by factors like industrial emissions and GDP. Results also demonstrate a distinct relationship between a country's CO2 emissions and its physical and socioeconomic factors. Specifically, the nation's coastline length, population density in coastal regions, and the diversity of its climatic conditions significantly influence its carbon footprint.

Discovery of new quinoline and isatine derivatives as potential VEGFR-2 inhibitors: design, synthesis, antiproliferative, docking and MD simulation studies.

A new set of quinoline and isatine derivatives were synthesized as antiangiogenic VEGFR-2 inhibitors. On a biological level, the in vitro ability of the obtained candidates to inhibit VEGFR-2 was found to be strong with IC50 values in the range of 76.64-175.50 nM. To investigate the cytotoxicity and safety, all compounds were tested against a panel of four cancer cell lines (A549, Caco2, HepG2 and MDA) as well as two normal cell lines (Vero and WI-38). Interestingly, compound 12 exhibited noticeable cytotoxicity against A549, Caco2 and MDA with IC50 values of 5.40, 0.58 and 0.94 µM, respectively. These results were better and comparable to that of doxorubicin (0.70, 0.82 and 0.90 µM, respectively) with more than three folds higher selectivity index against the Caco2 cell lines. Compound 9 prevented the healing of the cancer cells at a low concentration. Also, the compound's potential to induce programmed cell death in Caco-2 was proved through the significant down regulating of the expression of Bcl2, Bcl-xl and Survivin in addition to the slight upregulation of the TGF-ß gene. The cell cycle analysis indicated that compound 9 arrested the Caco-2 cells in the G2/M phase. Interestingly, the molecular docking studies against VEGFR-2 revealed the correct binding of the targeted compounds similar to sorafenib. Furthermore, MD experiments validated the binding of compound 12 with VEGFR-2 over 100 ns, as well as MM-PBSA analysis that confirmed the precise binding with optimum energy. Finally, ADMET analysis showed the general drug-likeness and confirmed the safety of the tested compounds.Communicated by Ramaswamy H. Sarma.

Assessment of air pollution at Greater Cairo in relation to the spatial variability of surface urban heat island.

Greater Cairo, Egypt, which lies in the apex of the Nile Delta, is one of the most populated regions in the world. Air pollution is a profound environmental issue prevailing in the urban/rural landscapes of this crowded megacity. The objectives of the present study were to utilize remotely sensed data in order to address the seasonal variations of the nocturnal surface urban heat island intensity (SUHII) as extracted from the American Moderate Resolution Imaging Spectroradiometer (MODIS) satellite and the related seasonal distribution of selected air pollutants, including nitrogen dioxide (NO2), sulphur dioxide (SO2), and carbon monoxide (CO) as extracted from the European TROPOspheric Monitoring Instrument (TROPOMI) for the period from 2018 to 2021. It is observed that there is clear nocturnal urban heat island over Greater Cairo, particularly at the administrative districts dominated by urban land use with high density of population and at the industrial and power generation locations. The highest SUHII is observed during winter. On the other hand, the selected pollutants also represent an urban pollution island (UPI) capping the regions of high SUHII. At the seasonal level, the highest NO2 correlation with the SUHII occurs during spring (R2 = 0.59), while the CO correlates maximum during winter (R2 = 0.51). Nonetheless, the seasonal SO2 distribution is poorly related to the SUHII as this specific pollutant is significantly associated with the industrial land use. Climatic and topographic factors could intensify the distribution of air pollution in the study area. Results of this study demonstrate the significance of geospatial technology tools in the subtle analysis and addressing regional air pollution. The outputs are also of a paramount implication on the management of urban environment and the adaptation of urban air quality.

Ecotoxicological assessment of toxic elements contamination in mangrove ecosystem along the Red Sea coast, Egypt.

Identifying biochemical aspects of the potentially toxic elements (PTEs) is of particular concern in mangrove ecosystems, Avicennia marina (Forssk.) Vierh., due to their importance as natural buffers in coastal areas. Nonetheless, the microbial community dynamics and potential scavenging responses of mangrove ecosystems to the phytotoxicity of PTEs remain questionable. This study assesses the ecological risk benchmarks of some PTEs, including aluminum (Al), boron (B), barium (Ba), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), mercury (Hg), manganese (Mn), nickel (Ni), lead (Pb), and zinc (Zn), and their microbial responses in the bottom sediments of mangrove ecosystems along Egypt's Red Sea coast. In particular, we assessed the role of microbial metabolites in biochemical cycling of nutrients and scavenging against phytotoxicity hazards. We quantified a spectrum of ecological risk assessment indices, which suggested elevated levels of PTEs in sediment, particularly Cr, Hg, and Pb. Canonical correspondence analysis and generalized linear mixed effects models indicate that the spatial biodiversity of microbial taxa is impacted significantly by the physicochemical characteristics of sediments and concentrations of PTEs. Results demonstrate that the microbial communities and their metabolites exert a significant influence on organic matter (OM) decomposition and the biochemical cycling of phytoavailable nutrients including nitrogen (N), phosphorus (P), and potassium (K). Spatially, nitrogenase activities were higher (411.5 µmoL h-1 mL-1) in the southern sites of the Red Sea coast relative to the northern locations (93.8 µmoL h-1 mL-1). In contrast, higher concentrations of phytohormones, including indole-3-acetic acid (IAA) (61.5 mg mL-1) and gibberellins (534.2 mg mL-1), were more evident in northern sites. Siderophores correlated positively with Fe concentration in sediments and averaged 307.4 mg mL-1. Overall, these findings provide insights into the biochemical signals of PTEs contamination in hostile environments, contributing to a better understanding of the future prospects of PTEs bioremediation in contaminated coastal environments.

Design, synthesis, anti-proliferative evaluation, docking, and MD simulations studies of new thiazolidine-2,4-diones targeting VEGFR-2 and apoptosis pathway.

We report herein, the design and synthesis of thiazolidine-2,4-diones derivatives as new inhibitors for VEGFR-2. The designed members were assessed for their in vitro anticancer activity against four cancer cell lines; A549, Caco-2, HepG-2 and MDA-MB-231. Compound 14a showed the most potent effects against Caco-2, and HepG-2 cell lines (IC50 = of 1.5 and 31.5 µM, respectively). Next, the in vitro VEGFR-2 inhibitory activity, safety profiles and selectivity indices were examined for all the synthesized members against the normal Vero cell line. Compound 14a (the safest member against Caco-2 cell line) was further investigated for its ability to inhibit Caco-2 cells migration and healing. Moreover, the apoptotic induction of compound 14a against Caco-2 cell line was investigated by assessing against four apoptotic genes (Bcl2, Bcl-xl, TGF, and Survivin). The results revealed that compound 14a can exert apoptosis through significant reduction of Bcl2, Survivin, and TGF gene expression levels. Finally, deep computational studies including molecular docking, ADMET, toxicity studies, and MD simulation were carried out. Also, the DFT calculations were performed and discussed, and the results confirmed the inhibitory reactivity of 14a against VEGFR-2. Compound 14a is expected to be used as a potential lead in the development of new VEGFR-2 inhibitors with increased potency.

Demographic and socioeconomic determinants of COVID-19 across Oman - A geospatial modelling approach.

Local, bivariate relationships between coronavirus 2019 (COVID-19) infection rates and a set of demographic and socioeconomic variables were explored at the district level in Oman. To limit multicollinearity a principal component analysis was conducted, the results of which showed that three components together could explain 65% of the total variance that were therefore subjected to further study. Comparison of a generalized linear model (GLM) and geographically weighted regression (GWR) indicated an improvement in model performance using GWR (goodness of fit=93%) compared to GLM (goodness of fit=86%). The local coefficient of determination (R2) showed a significant influence of specific demographic and socioeconomic factors on COVID-19, including percentages of Omani and non-Omani population at various age levels; spatial interaction; population density; number of hospital beds; total number of households; purchasing power; and purchasing power per km2. No direct correlation between COVID- 19 rates and health facilities distribution or tobacco usage. This study suggests that Poisson regression using GWR and GLM can address unobserved spatial non-stationary relationships. Findings of this study can promote current understanding of the demographic and socioeconomic variables impacting the spatial patterns of COVID-19 in Oman, allowing local and national authorities to adopt more appropriate strategies to cope with this pandemic in the future and also to allocate more effective prevention resources.

The impact of COVID-19 lockdowns on surface urban heat island changes and air-quality improvements across 21 major cities in the Middle East.

This study investigates changes in air quality conditions during the restricted COVID-19 lockdown period in 2020 across 21 metropolitan areas in the Middle East and how these relate to surface urban heat island (SUHI) characteristics. Based on satellite observations of atmospheric gases from Sentinel-5, results indicate significant reductions in the levels of atmospheric pollutants, particularly nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO). Air quality improved significantly during the middle phases of the lockdown (April and May), especially in small metropolitan cities like Amman, Beirut, and Jeddah, while it was less significant in "mega" cities like Cairo, Tehran, and Istanbul. For example, the concentrations of NO2 in Amman, Beirut, and Jeddah decreased by -56.6%, -43.4%, and -32.3%, respectively, during April 2020, compared to April 2019. Rather, there was a small decrease in NO2 levels in megacities like Tehran (-0.9%) and Cairo (-3.1%). Notably, during the lockdown period, there was a decrease in the mean intensity of nighttime SUHI, while the mean intensity of daytime SUHI experienced either an increase or a slight decrease across these locations. Together with the Gulf metropolitans (e.g. Kuwait, Dubai, and Muscat), the megacities (e.g. Tehran, Ankara, and Istanbul) exhibited anomalous increases in the intensity of daytime SUHI, which may exceed 2 °C. Statistical relationships were established to explore the association between changes in the mean intensity and the hotspot area in each metropolitan location during the lockdown. The findings indicate that the mean intensity of SUHI and the spatial extension of hotspot areas within each metropolitan had a statistically significant negative relationship, with Pearson's r values generally exceeding - 0.55, especially for daytime SUHI. This negative dependency was evident for both daytime and nighttime SUHI during all months of the lockdown. Our findings demonstrate that the decrease in primary pollutant levels during the lockdown contributed to the decrease in the intensity of nighttime SUHIs in the Middle East, especially in April and May. Changes in the characteristics of SUHIs during the lockdown period should be interpreted in the context of long-term climate change, rather than just the consequence of restrictive measures. This is simply because short-term air quality improvements were insufficient to generate meaningful changes in the region's urban climate.

Dating historical droughts from religious ceremonies, the international pro pluvia rogation database.

Climate proxy data are required for improved understanding of climate variability and change in the pre-instrumental period. We present the first international initiative to compile and share information on pro pluvia rogation ceremonies, which is a well-studied proxy of agricultural drought. Currently, the database has more than 3500 dates of celebration of rogation ceremonies, providing information for 153 locations across 11 countries spanning the period from 1333 to 1949. This product provides data for better understanding of the pre-instrumental drought variability, validating natural proxies and model simulations, and multi-proxy rainfall reconstructions, amongst other climatic exercises. The database is freely available and can be easily accessed and visualized via http://inpro.unizar.es/ .

Purification, Characterization, Identification, and Anticancer Activity of a Circular Bacteriocin From Enterococcus thailandicus.

New anticancer agents are continually needed because cancerous cells continue to evolve resistance to the currently available chemotherapeutic agents. The aim of the present study was to screen, purify and characterize a hepatotoxic bacteriocin from Enterococcus species. The production of bacteriocin from the Enterococcus isolates was achieved based on their antibacterial activity against indicator reference strains. Enterococcus isolates showed a broad spectrum of antibacterial activity by forming inhibition zones with diameters ranged between 12 and 29 mm. The most potent bacteriocin producing strain was molecularly identified as Enterococcus thailandicus. The crude extracted bacteriocin was purified by cation exchange and size exclusion chromatography that resulted in 83 fractions. Among them, 18 factions were considered as bacteriocins based on their positive antibacterial effects. The anticancer effects of the purified bacteriocins were tested against HepG2 cell line. The most promising enterocin (LNS18) showed the highest anticancer effects against HepG2 cells (with 75.24% cellular inhibition percentages), with IC50 value 15.643 µM and without any significant cytotoxic effects on normal fibroblast cells (BJ ATCC® CRL-2522™). The mode of anticancer action of enterocin LNS18 against HepG2 cells could be explained by its efficacy to induce cellular ROS, decrease HepG2 CD markers and arrest cells in G0 phase. Amino acid sequence of enterocin LNS18 was determined and the deduced peptide of the structural gene showed 86 amino acids that shared 94.7% identity with enterocin NKR-5-3B from E. faecium. Enterocin LNS18 consisted of 6 α-helices; 5 circular and one linear. Model-template alignment constructed between enterocin LNS18 and NKR-5-3B revealed 95.31% identity. The predicted 3D homology model of LNS18, after circularization and release of 22 amino acids, showed the formation of a bond between Leu23 and Trp86 amino acid residues at the site of circularization. Furthermore, areas of positive charges were due to the presence of 6 lysine residues resulting in a net positive charge of +4 on the bacteriocin surface. Based on the above mentioned results, our characterized bacteriocin is a promising agent to target liver cancer without any significant toxic effects on normal cell lines.

Spatiotemporal Assessment of COVID-19 Spread over Oman Using GIS Techniques.

Coronavirus disease (COVID-19), caused by acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a worldwide challenge effecting millions of people in more than 210 countries, including the Sultanate of Oman (Oman). Spatiotemporal analysis was adopted to explore the spatial patterns of the spread of COVID-19 during the period from 29th April to 30th June 2020. Our assessment was made using five geospatial techniques within a Geographical Information System (GIS) context, including a weighted mean centre (WMC), standard deviational ellipses, Moran's I autocorrelation coefficient, Getis-Ord General-G high/low clustering, and Getis-Ord G i ∗ statistic. The Moran's I-/G- statistics proved that COVID-19 cases in datasets (numbers of cases) were clustered throughout the study period. The Moran's I and Z scores were above the 2.25 threshold (a confidence level above 95%), ranging from 2274 cases on 29th April to 40,070 cases on 30th June 2020. The results of G i ∗ showed varying rates of infections, with a large spatial variability between the different wilayats (district). The epidemic situation in some wilayats, such as Mutrah, As-Seeb, and Bowsher in the Muscat Governorate, was more severe, with Z score higher than 5, and the current transmission still presents an increasing trend. This study indicated that the directional pattern of COVID-19 cases has moved from northeast to northwest and southwest, with the total impacted region increasing over time. Also, the results indicate that the rate of COVID-19 infections is higher in the most populated areas. The findings of this paper provide a solid basis for future study by investigating the most resolute hotspots in more detail and may help decision-makers identify targeted zones for alleviation plans. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s41748-020-00194-2.

A multidecadal assessment of climate indices over Europe.

Monitoring and management of several environmental and socioeconomic sectors require climate data that can be summarized using a set of standard and meaningful climate metrics. This study describes a newly developed gridded dataset for the whole of Europe, which employed a set of 125 climate indices spanning different periods based on data availability, but mainly 1950-2017 and 1979-2017. This dataset comprehensively summarizes climate variability in Europe for a wide range of climate variables and conditions, including air temperature, precipitation, biometeorology, aridity, continentality, drought, amongst others. Climate indices were computed at different temporal scales (i.e. monthly, seasonal and annual) and mapped at a grid interval of 0.25°. We intend to update these indices on an annual basis. This dataset is freely available to research and end-user communities.