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Novel thalidomide analogs as anticancer immunomodulatory agents.

Due to the constant increase in the number of plant diseases and the lack of available treatments, there has been a growing interest in plant extracts over the past few decades. Numerous studies suggest that plant extract molecules possess valuable antimicrobial activities, particularly against fungi and bacteria. This suggests that these biomaterials could potentially serve as attractive therapeutic options for the treatment of phytopathogen infections. In the present study, we investigated and analyzed the methanolic extract of Eryngium campestre L. whole plant extract using HPLC. The analysis revealed the presence of several polyphenolic constituents, with benzoic acid, catechol, quercetin, vanillic acid, resveratrol, naringenin, and quinol being the most abundant. The amounts of these constituents were determined to be 2135.53, 626.728, 579.048, 356.489, 323.41, 153.038, and 128.77 mg/kg, respectively. Furthermore, we isolated and identified different plant fungal and bacterial isolates from symptomatic potato plants, which were accessioned as Rhizoctonia solani (OQ880458), Fusarium oxysporum (OQ820156) and Fusarium solani (OQ891085), Ralstonia solanacearum (OQ878653), Dickeya solani (OQ878655), and Pectobacterium carotovorum (OQ878656). The antifungal activity of the extract was assessed using fungal growth inhibitions (FGI) at concentrations of 100, 200, and 300 µg/mL. The results showed that at the lowest concentration tested (100 µg/mL), the extract exhibited the highest effectiveness against R. solani with an FGI of 78.52%, while it was least effective against F. solani with an FGI of 61.85%. At the highest concentration tested, the extract demonstrated the highest effectiveness against R. solani and F. oxysporum, with FGIs of 88.89% and 77.04%, respectively. Additionally, the extract displayed a concentration-dependent inhibitory effect on all three bacterial pathogens. At the highest concentration tested (3000 µg/mL), the extract was able to inhibit the growth of all three bacterial pathogens, although the inhibition zone diameter varied. Among the bacterial pathogens, D. solani exhibited the highest sensitivity to the extract, as it showed the largest inhibition zone diameter at most of the extract concentrations. These findings highlight the potential of the E. campestre extract as a source of natural antimicrobial agents for controlling various plant pathogens. Consequently, it offers a safer alternative to the currently employed protective methods for plant disease management.

As an extension to our previous work for the development of new thalidomide analogs, the current work offers new insights into the immunomodulatory and anticancer activities of quinazolinone based molecules carrying a glutarimide moiety. The findings confirmed some previous findings and revealed some new information. Among the newly synthesized compounds, compounds 7d and 12 showed considerable immunomodulatory properties in comparison to thalidomide. 7d and 12 significantly reduced TNF-α levels in HepG-2 cells from 162.5 pg/mL to 57.4 pg/mL and 49.2 pg/mL, respectively compared to 53.1 pg/mL reported for thalidomide. Moreover, they caused 69.33% and 77.74% reduction in NF-κB P65, respectively, compared to 60.26% reduction for thalidomide. Similarly, they reduced VEGF from 432.5 pg/mL to 161.3 pg/mL and 132.8 pg/mL, respectively, in comparison to 153.2 pg/mL reported for thalidomide. The two new derivatives, 7d and 12 also showed about 8-fold increases in caspase-8 levels in cells treated with them. These results were slightly better than those of thalidomide. The obtained results revealed that Compound 12 had better immunomodulatory properties than thalidomide, with stronger effects on TNF-α, NF-B P65, VEGF, and caspase-8. Accordingly, this work indicates that compound 12 has interesting biological properties that should be further evaluated and modified in order to develop clinically useful thalidomide analogs.

This study examined the effects of nucleotide supplementation on broiler chick growth performance, immunological response, carcass traits, meat quality, serum biochemical parameters, total antioxidant capacity, intestinal morphology, mortality rate, and economic efficiency measures of broiler chicks. A total of 180 one-day-old chicks (Ross 308) were distributed into 6 groups, each of which consisted of 30 chicks, and each group was divided into 3 replicates so that each replicate contained 10 chicks fed on six experimental diets as follows: basal diet without oil or nucleotide (T1), basal diet with 1% soybean oil and without nucleotide(T2), 50 grams nucleotide per 100-kilogram diet with different fat sources (no oil(T3), 1% soybean oil(T4), 1% linseed oil(T5) &1% fish oil(T6) respectively during the experimental period (5 weeks). Growth performance parameters were detected per stage period. Four chicks from each replicate were used at the termination of the experiment for analysis of the above mentioned measurements. Results revealed that supplementation of nucleotide in diets of broiler chicks improved feed conversion ratio, carcass traits, intestinal morphology, serum biochemical parameters, immunological response, bursa of Fabricius weight, and the best ratios were observed in groups fed nucleotide in combination with fish and linseed oil. Also, there was an increased economic efficiency in the SBO fed group(T2) then group fed nucleotides in mix with linseed oil (T5) and control (T1). In comparison to the control groups (T1 & T2), groups fed nucleotides and PUFA oil sources had significantly lower n-6: n-3 ratio in breast muscle, and mortality rate.

Syzygium aromaticum L. (S. aromaticum) used universally as a spice beside as one of classical Indian and Chinese medicine. It contains a variety of biologically active substances, one of them is eugenol which the main component, accounting for 81.1% of the clove oil. It used in traditional medicine as an antibacterial, antineoplastic, antiseptic, and analgesic agent. Previous studies reported its role within photochemical reactions and its antioxidant, anti-inflammatory, antiviral, and insecticidal properties, for that, eugenol listed as a promising candidate for the chemical scaffold for pharmaceuticals. The aim of the current study is evaluating of methanolic (80%) clove extract at room temperature in the sunlight (RS) and at low temperatures in the dark (DC) for their antibacterial and anticancer activity applied on different two cancer cell line types breast carcinoma cell line (MCF-7) and hepato-carcinoma cell line type (HePG-2). The results evaluated that both (DC) and (RS) have antibacterial activity against five multidrug-resistant (MDR) isolates. Extract (DC) of clove has a larger zone of inhibition against S. aureus, S. epidermidis, P. aeruginosa, K. pneumonia, and E. coli, with diameter 13, 20, 20, 21, and 15 mm, respectively, with MICs and MBCs of 6.25 mg/mL and 12.5 mg/ml for all isolates except S. aureus showed MIC at 12.5 mg/ml. On the other hand, extract (RS) exhibit zone of inhibition with diameter 17, 10, 15, 18, 17 mm, respectively, with MICs and MBCs of 12.5 mg/mL and 25 mg/ml for all isolates except S. aureus showed MIC at 25 mg/ml. Also, both (DC) and (RS) have cytotoxic activity against two cell lines with significant DNA fragmentation as an indicator of cell apoptosis. The cytotoxic concentration of (DC) with IC50 values for MCF-7 started at 250 µg/ml and reached 46.7% but was 500 and 1000 µg/ml. toxicity reached 100%. Cytotoxicity of (RS) against mcf7 was found to be 48.25% at a concentration of 500 μg/ml, reaching 100% toxicity at the above concentrations 1000 µg/ml. For the HepG-2 cell line, the cytotoxic activity of (DC) was significant at 50.5% at a concentration of 250 µg/ml, whereas RS showed cytotoxic activity at 500 µg/ml with a value of 17.3%. These therapies for cancer and bacterial infections are all-natural and eco-friendly.

This work was carried out to investigate the effect of dietary supplementation of fish oil on growth performance, carcass quality, immunological and serum biochemical parameters, total antioxidant capacity, intestinal morphology, mortality ratio and economic efficiency measures of broiler chicks. A total of 150 (ross 308) one day old chicks was distributed into 5 groups each contains 3 replicates (10 chicks/ replicate) fed on Five experimental diets contains different level of oils (0 oil, 1(SBO & FO), 2 FO and 3% FO respectively), during the experimental period (5 weeks). four chicks from each replicate were used for analysis of the experimental chicks. The results revealed that supplementation of fish oil in diets of broiler chicks 1,2 and 3 % improve (P< 0.05) the body weight (Bw) and body weight gain (BWG) than control groups but the best value were observed in 1&3% fish oil group beside improvement of feed conversion ratio (FCR) in all groups fed fish oil than control groups. However, numerically increased feed consumption in 1% SBO fed group than other groups. Significant (P< 0.05) improvement of carcass characteristics and dressing percentage gradually with fish oil supplementation. The values of USFA and n-3 PUFA were significantly (P< 0.05) higher in the breast muscle of broilers fed with fish oil compared to the control groups. But, SFA significantly (P< 0.05) decreased with fish oil than control groups. No significant difference in n-6 PUFA value between SBO and FO groups. So, N- 6:N3 ratio in breast meat decreased gradually with FO addition. Also, triglycerides, cholesterol, LDL and VLDL concentrations were significantly (P< 0.05) reduced by fish oil treatments, but serum HDL-c, total protein (TP), and globulin (GL) concentrations were significantly (P< 0.05) increased by using diets containing fish oil. Also, provision of fish oil Significantly (P< 0.05) improves immune response in broilers chicken against Newcastle virus vaccine through increase antibody titer and TLC with decreased mortality rate. Significant (P< 0.05) improvement of intestinal morphology with fish oil supplement were detected. The highest economic efficiency was recorded in group fed 1% FO followed by 1% SBO, 2% FO, 3% FO,0% oil gradually. from the present study, it could be concluded that the supplementation of fish oil in chick's diets significantly improve the growth performance, body composition, immune response, serum biochemical parameters, intestinal morphology, decrease the mortality rate and economically efficient at rate 1% addition

Cancer is still a dangerous disease with a high mortality rate all over the world. In our attempt to develop potential anticancer candidates, new quinazoline and phthalazine based compounds were designed and synthesized. The new derivatives were built in line with the pharmacophoric features of thalidomide. The new derivatives as well as thalidomide were examined against three cancer cell lines, namely: hepatocellular carcinoma (HepG-2), breast cancer (MCF-7) and prostate cancer (PC3). Then the effects on the expression levels of caspase-8, VEGF, NF-κB P65, and TNF-α in HepG-2 cells were evaluated. The biological data revealed the high importance of phthalazine based compounds (24a-c), which were far better than thalidomide with regard to the antiproliferative activity. 24b showed IC

The present study aimed to investigate the effect of early access to feed and water post-hatch on broiler chicks' performance. One hundred and twenty chicks were transferred from the hatchery to the rearing house and randomly divided into two groups. The first group: chicks were immediately access to feed and water (F-time 0). The second group: was held without feed and water for 24 h (F-time 24). Then, feed and water were provided

Retinoblastoma (RB) is the most common primary intraocular malignant tumor in children. RB is mostly caused by biallelic mutations in RB1 and occurs in hereditary and non-hereditary forms according to the "two-hit" theory. RB1 mutations comprise point mutations, indels, large deletions, and duplications. Genetic testing is essential for the comprehensive treatment and management of patients with RB.The aim was to evaluate RB1 copy number variations (CNVs) using MLPA versus FISH assays in group of Egyptian patients with RB.16.67% showed an RB1 deletion, abnormal methylation status, or both.Our results suggested MLPA is a fast, reliable, and powerful method and should be used as a first-line screening tool for detecting RB1 CNVs in patients with RB. Moreover, MLPA is advantageous as it evaluates the methylation status/inactivation of RB1, not possible by FISH.

This work is one of our efforts to discover potent anticancer agents. We modified the most promising derivative of our previous work concerned with the development of VEGFR-2 inhibitor candidates. Thirteen new compounds based on benzoxazole moiety were synthesized and evaluated against three human cancer cell lines, namely, breast cancer (MCF-7), colorectal carcinoma (HCT116), and hepatocellular carcinoma (HepG2). The synthesized compounds were also evaluated against VEGFR-2 kinase activity. The biological testing fallouts showed that compound 8d was more potent than standard sorafenib. Such compound showed IC50 values of 3.43, 2.79, and 2.43 µM against the aforementioned cancer cell lines, respectively, compared to IC50 values of 4.21, 5.30, and 3.40 µM reported for sorafenib. Compound 8d also was found to exert exceptional VEGFR-2 inhibition activity with an IC50 value of 0.0554 μM compared to sorafenib (0.0782 μM). In addition, compound 8h revealed excellent cytotoxic effects with IC50 values of 3.53, 2.94, and 2.76 µM against experienced cell lines, respectively. Furthermore, compounds 8a and 8e were found to inhibit VEGFR-2 kinase activity with IC50 values of 0.0579 and 0.0741 μM, exceeding that of sorafenib. Compound 8d showed a significant apoptotic effect and arrested the HepG2 cells at the pre-G1 phase. In addition, it exerted a significant inhibition for TNF-α (90.54%) and of IL-6 (92.19%) compared to dexamethasone (93.15%). The molecular docking studies showed that the binding pattern of the new compounds to VEGFR-2 kinase was similar to that of sorafenib.

Background The widespread nature of coronavirus disease 2019 (COVID-19) has been unprecedented. We sought to analyze its global impact with a survey on colorectal cancer (CRC) care during the pandemic. Methods The impact of COVID-19 on preoperative assessment, elective surgery, and postoperative management of CRC patients was explored by a 35-item survey, which was distributed worldwide to members of surgical societies with an interest in CRC care. Respondents were divided into two comparator groups: 1) ‘delay’ group: CRC care affected by the pandemic; 2) ‘no delay’ group: unaltered CRC practice. Results A total of 1,051 respondents from 84 countries completed the survey. No substantial differences in demographics were found between the ‘delay’ (745, 70.9%) and ‘no delay’ (306, 29.1%) groups. Suspension of multidisciplinary team meetings, staff members quarantined or relocated to COVID-19 units, units fully dedicated to COVID-19 care, personal protective equipment not readily available were factors significantly associated to delays in endoscopy, radiology, surgery, histopathology and prolonged chemoradiation therapy-to-surgery intervals. In the ‘delay’ group, 48.9% of respondents reported a change in the initial surgical plan and 26.3% reported a shift from elective to urgent operations. Recovery of CRC care was associated with the status of the outbreak. Practicing in COVID-free units, no change in operative slots and staff members not relocated to COVID-19 units were statistically associated with unaltered CRC care in the ‘no delay’ group, while the geographical distribution was not. Conclusions Global changes in diagnostic and therapeutic CRC practices were evident. Changes were associated with differences in health-care delivery systems, hospital’s preparedness, resources availability, and local COVID-19 prevalence rather than geographical factors. Strategic planning is required to optimize CRC care., Global changes in both diagnostic and therapeutic practices in colorectal cancer care were evident in this survey conducted to analyze the impact of COVID-19 outbreak. The importance of this finding is that changes were associated with differences in health care delivery systems, hospital’s preparedness, resources availability, and local COVID-19 prevalence rather than geographical variations.

This trial was conducted to investigate the effects of multi-carbohydrase supplementation on the performance, carcase traits, intestinal histomorphology, caecal microbiota and nutrient digestibility of broiler chickens fed diets with varying energy levels. A total of 400-day-old male chicks were allocated into eight dietary treatments in a 4 × 2 factorial arrangement with 5 replicates per treatment. There were 4 dietary energy levels (the standard breed recommendation and reductions of 50, 100 and 150 kcal/kg from the standard) with or without multi-carbohydrase supplementation. Reducing the energy level by 50 kcal/kg did not significantly impact the measured parameters compared to the standard recommendation while it is reducing by 100 and 150 kcal/kg resulted in significant decreases in the body weight (BW) by levels up to 4.41% and a significant increase in the feed conversion ratio (FCR) by levels up to 4.67%. Enzyme supplementation significantly improved the BW and FCR by 3.24% and 2.95%, respectively. Dietary energy lowered by 100–150 kcal/kg resulted in a significant decrease in the dressing (up to 2.42%), breast yield (up to 2.82%), fat pads (up to 8.72%), liver (up to 6.30%) percentages and coliform count (up to 28.5%). The digestibility of dry matter, crude protein, ether extract and gross energy was increased due to enzyme supplementation by 4.15, 3.50, 3.35 and 3.72%, respectively. In conclusion, broiler performance and carcase traits can be negatively impacted if the energy density is reduced by 100–150 kcal/kg diet. Enzyme supplementation can improve the performance and nutrient digestibility regardless of the dietary energy level.HIGHLIGHTS The metabolisable energy level can be reduced by 50 kcal/kg diets compared to the breed recommendation. Decreasing the energy level by 100 or 150 kcal/kg diet compared to breed recommendations resulted in a negative impact on the performance. Multicarbohydrase blend supplementation resulted in significant improvements in the performance and nutrient digestibility.

Regarding the crucial role of deubiquitinase (DUB) enzymes in many viruses, in particular, Adenovirus, HSV-1, coxsackievirus, and SARS-CoV-2, DUB inhibition was reported as an effective new approach to find new effective antiviral agents. In the present study, a new wave of 4-(2-nitrophenoxy)benzamide derivatives was designed and synthesized to fulfill the basic pharmacophoric features of DUB inhibitors. The molecular docking of the designed compounds against deubiquitinase enzymes of the aforementioned viruses was carried out. Significant molecular docking results directed us to conduct in vitro antiviral screening against the aforementioned viruses. The biological data showed very strong to strong antiviral activities with IC50 values ranging from 10.22 to 44.68 μM against Adenovirus, HSV-1, and coxsackievirus. Compounds 8c, 8d, 10b, and 8a were found to be the most potent against Adenovirus, HSV-1, coxsackievirus, and SAR-CoV-2, respectively. Also, the CC50 values of the examined compounds ranged from 72.93 to 120.50 μM. Finally, the in silico ADMET and toxicity studies demonstrated that the tested members have a good profile of drug-like properties. Furthermore, we concluded the structure–activity relationship (SAR) of the newly designed and synthesized compounds regarding their in vitro results, which may help medicinal chemists in further optimization to obtain more potential antiviral candidates in the near future as well.

Opuntia ficus-indica is gaining scientists’ and policy makers’ interest worldwide as drought tolerant crop adopted to marginal low fertile soils. Few studies were conducted to estimate its water management parameters under different soil-climate conditions. O.ficus-indica was planted in the experimental farm of City of Scientific Research and Technological Applications (SRTA-City, Alexandria, Egypt) under different irrigation scheduling applications. The study aimed to understand the effect of severe water deficit on crop development and water management related parameters. First irrigation scheduling (T1) applied irrigation with fixed amount of water (7.2 m3 ha-1 week-1). The second (T2), was applied when soil water content (SWC) became below 35% of field capacity (Ɵfc) in effective root zone. The third (T3), was conducted when SWC was below 30% of Ɵfc. The results revealed higher yield under T1 than T2 and T3. Water productivity was the lowest in T1 (0.62 kg m-3) and the highest in T3 (18.13 kg m-3). Actual crop evapotranspiration (ETa) was significantly higher in T3 (4.80 mm day-1), than T2 (4.56 mm day-1) and T1 (3.84 mm day-1). No significant difference was found in soil water content, canopy cover, crop coefficient among the applied irrigation scheduling. Average canopy cover was 13.63%, 11.08%, and 10.22% for T1, T2, and T3, respectively indicating early crop development stage. The corresponding crop coefficient (kc) was between 0.19 in T1 to 0.23 in T2 and 0.24 in T3. Further study is recommended to confirm obtained results and estimate ETa and kc under middle and end crop development stages.

The main goal of this study is to assess the technical viability of using cement dust as part of the fines percentage in the unbound granular base/subbase pavement layers’ and subgrade soil as a viable sustainable solution. This study investigates the effect of adding cement dust to five types of pavement road materials which are collected from different ongoing roadway construction projects (1) Reclaimed Asphalt Pavement (RAP), (2) crushed stone base aggregates, (3) blend of crushed stone base aggregates with RAP, (4) crushed stone subbase aggregates, and (5) sandy subgrade soil. The resilient modulus (Mr) is selected as the main characteristic for evaluating the investigated materials’ stiffness. The regression parameters (k1, k2, and k3) of the universal Mr prediction model are found by fitting the experimental results of Mr testing for two replicates per each material type. The results show that using 3–5% of cement dust improves the estimated Mr of the investigated base/subbase materials and subgrades at the anticipated field stresses by 8–21%., As a result the structural layer coefficients are enhanced by 11–17%. KENLAYER nonlinear damage analysis confirms that using 3–5% of cement dust improves the predicted rutting life by up to 12% and the fatigue life up to 27%. Based on a typical pavement structure, enhancing pavement base/subbase layers and subgrade soils with 3–5% of cement dust reduces asphalt layer thickness from 11.25 to 12.50% and increases base/subbase layer thickness from 8.75 to 12.50% to maintain the same predicted rutting and fatigue lives of the typical structure. This positively affects the total construction cost in addition to the ecological benefits.

Sugarcane represents the main cash crop in Upper Egypt. Area cultivated with sugarcane over 300,000 feds with average production 48 t/fed and total production may reach 16 million tons. The cost of labor has been increasing where the price is uncompetitive with the cost of mechanical harvesting with imported machines. Egypt needs to change its sugarcane harvesting methods from manual harvesting to mechanization to match the development occurred in similar countries. To mechanize sugarcane harvesting. Local cheap harvester should be manufactured considering our particular conditions. The study aimed to review and conclude some parameters the base cutter of a sugarcane harvester. The parameters, many include Physical and mechanical properties of sugar cane, cutting methods and types of knife edges, blade angles for cutting blades, cutting velocity (rotational speed) and forward velocity. Several researchers have been reviewing and reporting these parameters from variable point of views and variable objectives.

The current study designed to evaluate the effect of oligosaccharide supplemented diets on growth performance, histomorphometric changes, economic efficiency and genetic expression of some growth and immunity-relative genes. One hundred and twenty weaned male rabbits, six weeks of age of two breeds (NZW and APPRI) were randomly allocated into six equal groups; the first supplemented with 0.3% Mannan-oligosaccharide (MOS), the second supplemented with 0.05% Isomalto-oligosaccharide (IMO) and the third considered a control group. Each group contained ten equal replicates. The highest Final body weight and feed consumption were recorded in MOS and IMO groups compared with control. Fortified feed diet with IMO significantly increased duodenal villi area and length than MOS and control groups. At the same time, Spleen white bulb area and length were significantly higher in MOS and IMO than control. Supplementation of MOS and IMO significantly improved carcass traits, economic efficiency and induced certain modifications in some major key genes involved in the regulation of nutrients metabolism, immunity and growth in different tissues. In conclusion, dietary supplementation of MOS and IMO had a desirable positive impact on productive and economic efficiency in the rabbit.

Background: Accidents are common among children, although these accidents were not adequately managed by community. And lack of environmental safety worldwide child with retinoblastoma label to home accident. Aim: assessment of home accident among children with retinoblastoma. Design: descriptive analytic design. Setting: at cancer children hospital 57357and parent home. Sampling: A purposeful samples of 100 parents according to specific criteria Tools: three tools were used for data collection. First tool: was an interviewing Questionnaire, (a) Socio – demographic characteristics (b) Assessment of child health need and problem (c) Assessment of parent knowledge about retinoblastoma (d) Assessment parent knowledge and practice according to prevention of home accident. Second tool: Home environment observation check list for assessing the children home safety. Third tool: medical record analysis regarding diagnosis. Results: The most of parent had unsatisfactory 'knowledge about prevention of home accident among their children with retinoblastoma, the most of parent had inadequate practices related prevention of home accident among their children with retinoblastoma, unsafe home environmental measure around two third were unsafe home. Conclusion: the most of parent had unsatisfactory knowledge and inadequate practice to prevent home accident among their children with retinoblastoma, the most of parents had unsatisfactory knowledge about retinoblastoma. Also there is unsafely measure to provide safe home environment for their children. Recommendations: Implement health education regarding prevention of home accident among child with retinoblastoma, instruction of prevention of home accident, First aid training should be provided to parents as an essential need.

Based on quinazoline, quinoxaline, and nitrobenzene scaffolds and on pharmacophoric features of VEGFR-2 inhibitors, 17 novel compounds were designed and synthesised. VEGFR-2 IC50 values ranged from 60.00 to 123.85 nM for the new derivatives compared to 54.00 nM for sorafenib. Compounds 15a, 15b, and 15d showed IC50 from 17.39 to 47.10 µM against human cancer cell lines; hepatocellular carcinoma (HepG2), prostate cancer (PC3), and breast cancer (MCF-7). Meanwhile, the first in terms of VEGFR-2 inhibition was compound 15d which came second with regard to antitumor assay with IC50 = 24.10, 40.90, and 33.40 µM against aforementioned cell lines, respectively. Furthermore, Compound 15d increased apoptosis rate of HepG2 from 1.20 to 12.46% as it significantly increased levels of Caspase-3, BAX, and P53 from 49.6274, 40.62, and 42.84 to 561.427, 395.04, and 415.027 pg/mL, respectively. Moreover, 15d showed IC50 of 253 and 381 nM against HER2 and FGFR, respectively.

Based on quinazoline, quinoxaline, and nitrobenzene scaffolds and on pharmacophoric features of VEGFR-2 inhibitors, 17 novel compounds were designed and synthesised. VEGFR-2 IC50 values ranged from 60.00 to 123.85 nM for the new derivatives compared to 54.00 nM for sorafenib. Compounds 15a, 15b, and 15d showed IC50 from 17.39 to 47.10 µM against human cancer cell lines; hepatocellular carcinoma (HepG2), prostate cancer (PC3), and breast cancer (MCF-7). Meanwhile, the first in terms of VEGFR-2 inhibition was compound 15d which came second with regard to antitumor assay with IC50 = 24.10, 40.90, and 33.40 µM against aforementioned cell lines, respectively. Furthermore, Compound 15d increased apoptosis rate of HepG2 from 1.20 to 12.46% as it significantly increased levels of Caspase-3, BAX, and P53 from 49.6274, 40.62, and 42.84 to 561.427, 395.04, and 415.027 pg/mL, respectively. Moreover, 15d showed IC50 of 253 and 381 nM against HER2 and FGFR, respectively.

Based on quinazoline, quinoxaline, and nitrobenzene scaffolds and on pharmacophoric features of VEGFR-2 inhibitors, 17 novel compounds were designed and synthesised. VEGFR-2 IC50 values ranged from 60.00 to 123.85 nM for the new derivatives compared to 54.00 nM for sorafenib. Compounds 15a, 15b, and 15d showed IC50 from 17.39 to 47.10 µM against human cancer cell lines; hepatocellular carcinoma (HepG2), prostate cancer (PC3), and breast cancer (MCF-7). Meanwhile, the first in terms of VEGFR-2 inhibition was compound 15d which came second with regard to antitumor assay with IC50 = 24.10, 40.90, and 33.40 µM against aforementioned cell lines, respectively. Furthermore, Compound 15d increased apoptosis rate of HepG2 from 1.20 to 12.46% as it significantly increased levels of Caspase-3, BAX, and P53 from 49.6274, 40.62, and 42.84 to 561.427, 395.04, and 415.027 pg/mL, respectively. Moreover, 15d showed IC50 of 253 and 381 nM against HER2 and FGFR, respectively.

Taxol, a diterpenoid was initially isolated from the bark of Taxus brevifolia, approved by FDA in 1994 as a powerful drug for metastatic ovarian carcinoma, breast and lung cancer. However, due to limitations in the production of this drug based on this plant source, the productive potentiality of fungi of this compound opened a new avenue for its commercial production. In this study, among the twenty fungal isolates screened for Taxol production, Aspergillus terreus had the highest potentiality to produce Taxol (131.2 µg/ml). The productivity of Taxol by A. terreus has been maximized by nutritional optimization using inhibitors and growth regulators. The yield of Taxol by A. terreus was maximally obtained (0.663µg/ml) by growing the fungal isolate on potato dextrose broth medium, amended with addition of biotin at 150 µg/ml for 20 days. The chemical structure Taxol extracted of A. terreus has been verified by proton and carbon NMR, IR and UV analyses. The activity of A. terreus Taxol has been assessed towards multiple cell lines, displaying a strong anticancer activity. In conclusion, the productivity of Taxol by A. terreus has been greatly improved upon using biotin as chemical modulator, that open a new avenue for commercializing the Taxol yield by fungi.

The current study was directed toward developing a new series of fused heterocycles incorporating indazolylthiazole moiety. The newly synthesized compounds were characterized through elemental analysis and spectral data (IR, 1H-NMR, 13C-NMR, and Mass Spectrometry). The cytotoxic effect of the newly synthesized compounds was evaluated against normal human cells (HFB-4) and cancer cell lines (HepG-2 and Caco-2). Among the synthesized compounds, derivatives 4, and 6 revealed a significant selective antitumor activity, in a dose-dependent manner, against both HepG-2 and Caco-2 cell lines, with lower risk toward HFB-4 cells (normal cells). Derivative 8 revealed the maximum antitumor activity toward both tumor cell lines, with an SI value of about 26 and IC50 value of about 5.9 μg/mL. The effect of these derivatives (8, 4, and 6) upon the expression of 5 tumor regulating genes was studied through quantitative real-time PCR, where its interaction with these genes was simulated through the molecular docking study. Furthermore, the antimicrobial activity results revealed that compounds 2, 7, 8, and 9 have a potential antimicrobial activity, with maximum broad-spectrum activity through compound 3 against the three tested pathogens: Streptococcus mutans, Pseudomonas aeruginosa, and Candida albicans. The newly prepared compounds also revealed anti-biofilm formation activity with maximum activity against Streptococcus mutans, Pseudomonas aeruginosa, and Candida albicans, respectively.

Tungsten oxide WO3 nanoparticles (NPs) were prepared in a form of nanosheets with a homogeneous size and dimensions in one step through acid precipitation using a cation exchange column. The resulting WO3 nanosheets surface was decorated with one of the two amino acids (AAs) L-tryptophan (Trp) or L-cysteine (Cys) for their dye removal, antimicrobial, and antitumor activities. A noticeable improvement in the biological activity of WO3 NPs was detected upon amino acid modification compared to the original WO3. The prepared WO3-Trp and WO3-Cys exhibited strong dye removal activity toward methylene blue and safranin dyes with complete dye removal (100%) after 6 h. WO3-Cys NPs and WO3-Trp NPs revealed higher broad-spectrum antibacterial activity toward both G-ve and G+ve bacteria with strong antifungal activity toward Candida albicans. Anticancer results of the modified WO3-Cys and WO3-Trp NPs against various kinds of cancer cells including MCF-7, caco-2, and HepG-2 cells indicated that they have a potent effect in a dose-dependent manner with high selectivity to cancer cells and safety against normal cells. The expression levels of E2F2, Bcl-2 genes were found to be suppressed after treatment with both WO3-Cys and WO3-Trp NPs more than 5-FU-treated cells. While expression level of the p53 gene in all tested cells was evidently up-regulated after treatment by more than 5-8 folds as compared to untreated cells. The docking results confirmed the ability of both NPs to bind to P53 gene with relevant potency in binding to other tested gens and participation of cysteine SH-functional group in such interaction.

Palpebral capillary hemangioma is a benign tumor most often involving the skin of the eyelids. We report the case of a 15-year-old child with an isolated palpebral capillary hemangioma. Palpebral capillary hemangioma is a tumor that may require only surveillance with therapeutic abstention because in the majority of cases regression is spontaneous. Some authors recommend medical treatments such as systemic corticosteroids, beta-blockers and intra-tumoral corticosteroid injections.

Pregnancy is a risk factor for Valsalva retinopathy. We report a case of a 33 year old pregnant woman, who presented Valsalva retinopathy after an effort of defecation followed by constipation. The diagnosis should be made after eliminating other causes of hemorrhage. The evolution is usually spontaneously favorable.

Best disease is a hereditary-degenerative macular dystrophy. Described for the first time by Friedrich Best, It is due to the accumulation of lipofuscin in the macular pigment epithelium. We report a case of a 13 years old female with no medical history. Slit lamp examination revealed unremarkable findings in the anterior segment of both eyes. Posterior segment exam, at the macula, showed a well circumscribed yellow material similar to the egg yolk structure, in both eyes (Figure 1). Figure 1: Retinography with bilateral egg yolk-like image on macula. The Optical Coherence Tomography (OCT) macula revealed Pigmentary Epithelial Detachment (PED) and LE atrophic scar. The systemic examination had no remarkable findings. The patient was diagnosed Best Vitelliform macula.

Juvenile ankylosing spondylitis is a chronic arthropathy that predominantly affects boys after the age of 10 years. We report a clinical case of a 16 years old aged male, who presented in the emergency room with a painful red eye, severe photophobia, and tearing right eye. The slit lamp examination was showing unusual anterior uveitis with hypopyon. The visual acuity was 2/10 in the right eye. The slit lamp examination of the left eye was unremarkable. The clinical results were in favour of Juvenile ankylosing spondylitis (Figure 1).

Corneal perforation is a potentially devastating complication that can result from numerous conditions that precipitate corneal melting. We report a clinical of a 65 years old woman who has presented in the emergency room with a non traumatic corneal perforation, with expulsion of the lens. Complicated by the presence of a chronic antecedent of corneal ulcer (Figure 1).

Herpes zoster ophthalmic is a common condition in the elderly or in the immunocompromised people. We present the case of a 32-yearold female patient, without any particular history, who consulted the emergency room for a red right eye with major chemosis, palpebral edema, and decreased visual acuity. There was also a crusty rash in the V1 territory, suggesting herpes zoster. Visual acuity was 2/10 in the right eye and 10/10 left eye (Figure 1 and 2). Examination at the slit lamp revealed a non-hypertensive granulomatous anterior kerato-uveitis of the right eye. Given the severity of the lesion, an immunodepressive background was suspected, HIV serology came back positive.

ObjectivesMalaria infection is still known to be a worldwide public health problem, especially in tropical and sub-tropical African countries like Sudan. A pilot study conducted to describe the trend ofP. falciparumdrug resistance markers in 2017–2018 in comparison to CQ and AS/SP eras in Sudan. ThePfcrt,Pfmdr-1,Pfdhfr, andPfdhpsgenes were investigated. Data deposited by the worldwide antimalarial resistance network was consulted, and the molecular markers previously reported from Sudan were analyzed.ResultsDrug molecular markers analysis was successfully done on 20P. falciparumisolates. ThePfcrtK76 showed high frequency; 16 (80%). For thePfmdr-1,9 (45%) isolates were carrying the N86 allele, and 11 (55%) were 86Y allele. While the Y184F of thePfmdr-1showed a higher frequency of 184F compared to Y184; 16 (80%) and 4 (20%), respectively. In thePfdhfr, 51I allele showed higher frequency compared to N51; 18 (90%) and 2 (10%), respectively. For S108N, 18 (90%) were 108 N and 2 (10%) were S108. In thePfdhps, all isolates were carrying the mutant alleles; 437G and 540E. The frequency distribution of thePfcrt,Pfmdr-1,Pfdhfr,Pfdhpswas significantly different across the whole years in Sudan.

Background The aim of this study is to investigate whether the energy matrix values of the nonstarch polysaccharide- (NSP-) degrading enzymes, bioemulsifier (LYSOFORTE®), guanidinoacetic acid (CreAMINO®), or their combinations could be summed. The effects of these additives on the growth performance, carcass traits, and economic value of the broiler chicken diets were evaluated. A total of 525-one-day-old Ross chicks with an initial body weight of 42.96 ± 0.87 g were haphazardly allocated into seven groups with five replicates. The seven experimental treatments are as follows: (1) basal diet with no additives (breeder recommendation), which is the control group, (2) basal diet minus 100 kcal/kg supplemented with 0.02% NSP-degrading enzymes (NSP), (3) basal diet minus 50 kcal/kg supplemented with 0.025% emulsifier (LYSOFORTE®), (4) basal diet minus 50 kcal/kg supplemented with 0.06% guanidinoacetic acid (CreAMINO®), (5) basal diet minus 150 kcal/kg supplemented with a mixture of NSP and LYSOFORTE® (NSPL), (6) basal diet minus 100 kcal/kg supplemented with a mixture of NSP and CreAMINO® (NSPC), and (7) basal diet minus 200 kcal/kg supplemented with a mixture of NSP, LYSO, and CreAMINO® (NSPLC). The experiment lasted for 35 days. Results It was found that the final body weight, body weight gain, and relative growth rate were significantly higher in birds fed diets supplemented with NSPL, NSPC, CreAMINO, and LYSO with the reduced energy matrix value. The overall feed conversion ratio was significantly improved due to the supplementation of NSPC, CreAMINO, NSPL, and LYSO with the reduced energy matrix value compared to the control group. Moreover, no significant effect on the carcass criteria was observed by the different treatments. As a result of the dietary supplementation with NSPL, NSPC, CreAMINO®, and LYSO with the reduced energy matrix value, the net profit, total return, economic efficiency, and performance index were increased and the cost of feed per kg of body weight gain was decreased. Conclusion The energy matrix value of NSPL, NSPC, CreAMINO®, and LYSOFORTE could be established in the diets of broiler chickens to improve the growth performance and economic efficiency.

NASA launched the Space Radar Laboratory (SRL) on the two space shuttle missions of “Endeavor” in April and October of 1995. The purpose of these missions was to assess the utility of Shuttle Imaging Radar (SIR-C/X-SAR) for applications in geology, hydrology, agriculture, forestry, desert studies, oceanography and subsurface mapping. The data coverage for the Kingdom of Saudi Arabia from the two missions was processed and analyzed for their ability to show surface and subsurface expressions of drainage channels, or wadis. The processing of the images included removal of speckle, merging of radar with optical Landsat imagery, and color compositing for optimum contrast. The evaluation was carried out at two sites in the Nafud Al-Mazhur and in the southern margin of the Rub’al Khali. Results indicate that radar imagery has the potential to detect old river beds (wadis) buried under a thin cover of sand. It is therefore anticipated that the radar data will be useful in enhancing the present understanding of the hydrogeology and paleo-climate of the Arabian Peninsula.

Objectives: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. The aim of this study is to determine the association of IL-17A -197G/A polymorphism with RA in Sudanese Patients. A descriptive cross-sectional study was conducted between March and December, 2018. Clinical and demographic data of the study participants were collected and analysed. All statistical tests were considered as statistically significant when p Results: The study population included 266 participants, 166 (63.1%) were females [mean age 41.4 ± 15.5 years] and 97 (36.9%) were males [mean age 36.2 ± 16.0 years]. Of the 266 participants, 31% (85/266) were RA cases and 69% (181/266) were healthy controls. Prevalence of IL-17A genotypes among the study population was 52.6% (140/266) were AG heterozygote genotype, 38.4% (102/266) were AA homozygote genotype, and 9.0% (24/266) were GG homozygote genotype. Correlation of IL-17A genotypes was negatively statistically significant based on participants clinical status, and family history of RA, Pearson’s correlation [r = -0.392, P value 0.001] and [r = -0.226, P value 0.001], respectively, while positively statistically significant with gender, Pearson’s correlation [r = 0.140, P value 0.023]. Based on the duration of RA, no statistically significant correlation was observed, Pearson’s correlation [ r = -0.138, P value 0.207].

Objectives: IL-17A G197A and IL-17F A7488G polymorphisms has been identified to be associated with the susceptibility to many diseases. This study aimed to investigate the frequency distribution of IL-17A G197A and IL-17F A7488G polymorphisms among healthy Sudanese population. A descriptive cross-sectional hospital-based molecular study conducted in different sites throughout Sudan. Two ml blood samples were collected from 717 healthy participants. Demographic data and the medical history of the participants were collected.Results: Of the 717 participants, 355 (49.5%) were males and 362 (50.5%) were females, their mean age was 30.2±17.2 and 32.2±16.5, respectively. For IL-17A, the most frequent genotype detected among males and females was IL-17A heterozygote allele (AG); 215 (60.6%) and 194 (53.6%), respectively. Whereas, for IL-17F, the most frequent allele among males and females was the homozygote allele (AA); 298 (83.9%) for males and 322 (89.0%) for females. HWE for genotype distributions of IL-17A was showing statistical insignificance for IL-17A among males and females, P value 0.614. While HWE for IL-17F reached the equilibrium level, P value 0.048. The most frequent age group was those aged between 21 to 40 years; 281 (39.2%). Arab constituted the major ethnicity of the study participants; 418 (58.3%), P value 0.034.

The authors have requested that this preprint be removed from Research Square.

BackgroundThis study was performed to investigate the effect of Alpha-galactosidase (AlphaGal) supplementation with two energy levels on the growth performance, amino acid ileal digestibility coefficient “AID%,” economic value, intestinal histology, and blood biochemical parameters of broiler chickens. Two-hundred 3-day-old broiler chicks (average body weight 74.34 g ±0.52 Ross 308) were randomly assigned to a 2 × 2 factorial arrangement consisting of two energy diets groups: in the first group, the birds were fed on a recommended energy diet (RED) while the second group was reduced 120 kcal/kg diet as a low energy diet (LED) and two levels of AlphaGal (0 or 50 mg/kg diet) for RED and LED for the 35-day feeding period.ResultsThe interaction effects between the energy level and the AlphaGal supplementations resulted in significant decrease (P ≤ 0.05) in the body weight, body weight gain, and the relative growth rate. The feed conversion ratio was signficantly increased in LED without supplementation of AlphaGal group during the entire experimental period, this negative effect on the growth performance was corrected by AlphaGal supplementation. The AID% value was increased significantly by AlphaGal supplementation. Blood triglyceride concentrations were significantly decreased (P = 0.02) in the LED group with or without AlphaGal supplementation, while the level of high-density lipoprotein (HDL) was significantly decreased (P = 0.01) in the LED or RED groups supplemented with 50 mg RED AlphaGal. Histologically, the number of intestinal glands and goblet cells increased in both RED and LED groups supplemented with AlphaGal and their secretions were mainly neutral mucopolysaccharides and less acidic mucopolysaccharides.ConclusionAlphaGal supplementation improved the growth performance of broiler chickens fed LED and the growth performance is similar to those fed RED, thereby consequently improving the economic value of these diets. AlphaGal supplementation improves intestinal histology and morphology as well.

Background Malaria infection is still known to be a worldwide public health problem, especially in tropical and sub-tropical African countries like Sudan. The fight against malaria is still taking place due to many factors. One of these factors is the presence of Plasmodium falciparum drug resistant parasites. This study is aiming at studying the P. falciparum drug resistance markers and analyzing the historical literature on these markers in Sudan. Methods A descriptive cross-sectional healthcare-centers based study conducted in Khartoum state between December 2017 and July 2018. Febrile patients diagnosed with P. falciparum malaria infection were recruited. Two ml blood samples were collected prior to start treatment. Genotyping of the specific point mutations in the P. falciparum genome was done using Sanger sequencing method for the Pfcrt, Pfmdr-1, Pfdhfr, and Pfdhps genes. Data deposited by the worldwide antimalarial resistance network was consulted and the molecular markers previously reported from Sudan were identified, collected, and analyzed to compare between past and present frequency of malaria drug resistance mutations. One-way ANOVA test was used to calculate the least significance of frequency distribution in the molecular markers collected from the previous reports from Sudan in comparison to this study. Pearson correlation was used to investigate the association between the different drug resistance markers. Results Drug molecular markers analysis was successfully done on the 20 P. falciparum isolates. the Pfcrt K76 showed the highest frequency; 16 (80%). Pfcrt 76T was 4 (20%). For the Pfmdr-1 marker, 9 (45%) isolates were carrying the N86 allele and 11 (55%) were 86Y allele. While the Y184F of the Pfmdr-1 showed higher frequency of 184F compared to Y184; 16 (80%) and 4 (20%), respectively. Concerning the double Pfmdr-1 haplotype, NY haplotype was 2 (10%), NF was 7 (35%), YF was 9 (45%), and YY was 2 (10%). In the Pfdhfr , 51I allele showed higher frequency compared to N51; 18 (90%) and 2 (10%), respectively. Whereas for C59R, C59 was 18 (90%), and 59R was 2 (10%). For S108N, 18 (90%) for 108N and 2 (10%) for S108. The triplet haplotype ICN of the Pfdhfr ; was the most frequent haplotype; 16 (80%). Concerning the Pfdhps , all the 20 (100%) isolates were carrying the mutant alleles; 437G and 540E. the Pfdhps haplotype present was the double GE haplotype only. No statistically significant correlation was found for the Pfcrt , Pfmdr-1 , Pfdhfr , and Pfdhps . Historical reports on P. falciparum multidrug resistant collected from 1989 to 2016 showed extreme fluctuation. High prevalence of Pfcrt 76T allele was observed in Khartoum throughout all years of previous studies, while in Gedaref Pfcrt 76T showing increased prevalence each year. All studied genes were showing increase prevalence of the mutant alleles and reduction of the wildtype alleles. In this study, the GE mutant haplotype was prevalent in all the studied samples. Frequency distribution of the Pfcrt K76T and Pfmdr-1 N86Y alleles, Pfmdr-1 ; N86Y and Y184F, Pfdhfr ; N51I and S108N, and Pfdhps ; A437G and K540E double haplotypes was significantly different across the whole years in Sudan. Conclusion This study describes the distribution of P. falciparum multidrug resistance markers throughout Sudan providing a solid baseline data of the status of these markers which could be very useful for the malaria control program not only for establishing surveillance system that monitor the change in and/or the emergence of malaria drug resistance but it will also offer a guidance for the evidence-base decision-making regarding the treatment protocol national and regional wise.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by alternating periods of activity and remission. Evaluation of the clinical activity of SLE is important for choosing the correct treat¬ment. Current blood biomarkers for assessing SLE activity are not highly sensitive or specific to changes in disease activity. Therefore, the search for clinically useful markers of its activity is ongoing. This study aimed to evaluate serum beta-2 microglobulin (β2-MG) level in SLE patients and its relation to different clinical manifestations, laboratory parameters and disease activity using systemic lupus disease activity index (SLEDAI). The study included 40 SLE patients, divided according to SLEDAI into two groups: 20 active SLE patients with SLEDAI ≥4 and 20 inactive SLE patients with SLEDAI4. Also, 20 ages and sex matched apparently healthy individuals formed a control group. Serum β2-MG levels (mg/L) were measured by MININEPHPLUS. Furthermore, laboratory investigations and fundus examinations were performed. The study revealed a significant increase in serum β2-MG level in SLE patient groups (mean 6.77 ± 1.83 and 2.59 ± 0.43 mg/L), compared with the controls (0.82 ± 0.20mg/L, P=0.000), and its level increased in the active SLE group (mean 6.77 ± 1.83 mg/L) than in the inactive group of patients (mean 2.59 ± 0.43 mg/L). Serum β2-MG levels were significantly higher in SLE patients with arthritis, cutaneous and/or mucosal manifestations, Lupus nephritis, and cardiac manifestations but not in patients suffering from hematological, neurological or ocular manifestations. In active SLE patients, serum β2-MG levels correlated positively with SLEDAI, and ESR and correlated negatively with C3 and C4 complement. In conclusion, determination of β2-MG concentration in SLE patients may be helpful in assessing the disease activity as its serum level was higher in SLE patients especially those with active lupus and correlated with certain clinical and laboratory parameters.

Additional file 2: Table S2. Subgroup analysis of IL-17F genotypes distribution across the different Sudanese ethnic groups. M±Std: Mean Difference ± Standard Error. 95% CI [L-U]: 95% Confidence Interval [ Lower bound -Upper bound].

Additional file 1: Table S1. Numbers and drug molecular markers genotypes of P. falciparum isolates from Sudan 1989 – 2018.

Additional file 1: Table S1. Subgroup analysis of IL-17A genotypes distribution across the different Sudanese ethnic groups.

Additional file 2: Table S1. Statistical significance of Pfcrt K76T frequency distribution across the different previous studies conducted in Sudan. Table S2. Statistical significance of Pfmdr-1 N86Y frequency distribution across the different previous studies conducted in Sudan. Table S3. Statistical significance of Pfdhfr N51I and S108N double haplotype frequency distribution across the different previous studies conducted in Sudan. Table S4. Statistical significance of Pfdhps A437G and K540E double haplotype frequency distribution across the different previous studies conducted in Sudan. Table S5. Statistical significance of Pfmdr-1 N86Y and Y184F double haplotype frequency distribution across the different previous studies conducted in Sudan.