SYNTHESIS, ANTICANCER ACTIVITY AND MOLECULAR DOCKING STUDY OF NOVEL 1, 3-DIHETEROCYCLES INDOLE DERIVATIVES

Objective: The present work aimed to synthesize some new 1, 3-diheterocyles indolyl derivatives and study their cytotoxic activity. In addition, explore the probability of the most promising antiproliferative compounds to inhibit TopoI enzyme theoretically via molecular docking study.Methods: Reaction of ethyl 2-(3-formyl-1H-indol-1-yl)acetate (1) with 2-cyanoacetic acid hydrazide, 3-amino-5-pyrazolone and 2'-acetyl-2-cyanoacetohydrazide in an equal molar ratio led to the formation of compounds 2, 6, 8 and 10, respectively, which in turn reacted with another molecule of 2-cyanoacetic acid hydrazide and/or 3-amino-5-pyrazolone (1:1 molar ratio) to give novel series of 1,3-dipyrazole indole derivatives 3, 7, 9 and 11, respectively. On the other hand, Knoevenagel condensation of 1 with malononitrile gave ethyl 2-(3-(2, 2-dicyanovinyl)-1H-indol-1-yl) acetate (11). Reaction of 11 with 2-cyanoacetic acid hydrazide, 3-amino-5-pyrazolone, hydrazine hydrate, urea, thiourea and/or guanidine yielded 1, 6-diaminopyridine 12, pyrano(2,3-c)pyrazole 14, pyrazole 16 and pyrimidine derivatives 18a-c, respectively. Reaction of the latter compounds with 3-amino-5-pyrazolone furnished a novel series of 1, 3-diheterocycle indole derivatives 13, 15, 17 and 19a-c, respectively. Ten new target compounds 3, 6, 8, 10, 13, 15, 17 and 19a-c were tested for in vitro antiproliferative activity against A-549, MCF7, HCT-116 and HEPG2 cancer cell lines. In addition, molecular docking study of the most promising antiproliferative compounds against human DNA Topoisomerase I (PDB ID: 1T8I) theoretically is discussed.Results: Compounds 3, 6, 8 and 17 showed potent in vitro antiproliferative activity. Docking scores of the latter compounds were observed better than co-crystalline ligand.Conclusion: Further work is recommended to confirm the inhibition of TopoI in a specific bioassay

Biliary fistula and late recurrence of liver hydatid cyst: Role of cysto-biliary communication: A prospective multicenter study

Background: Hydatid cyst disease (HCD) is common in certain locations. Surgery is associated with postoperative biliary fistula (POBF) and recurrence. The primary aim of this study was to identify whether occult cysto-biliary communication (CBC) can predict recurrent HCD. The secondary aim was to assess the role of cystic fluid bilirubin and alkaline phosphatase (ALP) levels in predicting POBF and recurrent HCD. Aim: To identify whether occult CBC can predict recurrent HCD. The secondary aim was to assess the role of cystic fluid bilirubin and ALP levels in predicting POBF and recurrent HCD. Methods: From September 2010 to September 2016, a prospective multicenter study was undertaken involving 244 patients with solitary primary superficial stage cystic echinococcosis 2 and cystic echinococcosis 3b HCD who underwent laparoscopic partial cystectomy with omentoplasty. Univariable logistic regression analysis assessed independent factors determining biliary complications and recurrence. Results: There was a highly statistically significant association (P ≤ 0.001) between cystic fluid biochemical indices and the development of biliary complications (of 16 patients with POBF, 15 patients had high cyst fluid bilirubin and ALP levels), where patients with high bilirubin-ALP levels were 3405 times more likely to have biliary complications. There was a highly statistically significant association (P ≤ 0.001) between biliary complications, biochemical indices, and the occurrence of recurrent HCD (of 30 patients with recurrent HCD, 15 patients had high cyst fluid bilirubin and ALP; all 16 patients who had POBF later developed recurrent HCD), where patients who developed biliary complications and high bilirubin-ALP were 244.6 and 214 times more likely to have recurrent hydatid cysts, respectively. Conclusion: Occult CBC can predict recurrent HCD. Elevated cyst fluid bilirubin and ALP levels predicted POBF and recurrent HCD

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Electronic noses for monitoring benzene occupational exposure in biological samples of Egyptian workers

Objectives: Benzene is commonly emitted in several industries, leading to widespread environmental and occupational exposure hazards. While less toxic solvents have been substituted for benzene, it is still a component of petroleum products and is a trace impurity in industrial products resulting in continued higher occupational exposures in industrial settings in developing countries. Materials and Methods: We investigated the potential use of an electronic nose (e-nose) to monitor the headspace volatiles in biological samples from benzene-exposed Egyptian workers and non-exposed controls. The study population comprised 150 non-smoking male workers exposed to benzene and an equal number of matching non-exposed controls. We determined biomarkers of benzene used to estimate exposure and risk including: benzene in exhaled air and blood; and its urinary metabolites such as phenol and muconic acid using gas chromatography technique and a portable e-nose. Results: The average benzene concentration measured in the ambient air of the workplace of all studied industrial settings in Alexandria, Egypt; was 97.56±88.12 μg/m3 (range: 4.69–260.86 μg/m3). Levels of phenol and muconic acid were signifi cantly (p < 0.001) higher in both blood and urine of benzene-exposed workers as compared to non-exposed controls. Conclusions: The e-nose technology has successfully classifi ed and distinguished benzene-exposed workers from non-exposed controls for all measured samples of blood, urine and the exhaled air with a very high degree of precision. Thus, it will be a very useful tool for the low-cost mass screening and early detection of health hazards associated with the exposure to benzene in the industry

Sustained Functioning Impairments and Oxidative Stress with Neurobehavioral Dysfunction Associated with Oral Nicotine Exposure in the Brain of a Murine Model of Ehrlich Ascites Carcinoma: Modifying the Antioxidant Role of <i>Chlorella vulgaris</i>

Background: This study provides a model for studying the mechanism(s) responsible for the nervous tissue damage and misfunctioning that occurred due to oral nicotine exposure, considered a stress factor, during the presence of Ehrlich ascites carcinoma bearing in the mouse model (EAC). The mitigating role of Chlorella vulgaris (CV) against nicotine-induced brain damage was evaluated. Methods: Eighty Swiss female mice were classified into four groups, these were the control, the CV group, the nicotine group(100 µg/kg), and the combination group. Oxidant/antioxidant status, proinflammatory cytokines levels, DNA damage, quantitative microscopical lesions, and Caspase 3, Bcl-2 proteins were assessed in the current study. Levels of dopamine (DA) and gamma-aminobutyric acid (GABA) were also evaluated. Results: Nicotine was found to cause pronounced neurobehavioral alterations, increase the mortalities oxidative stress DNA damage, and augment the inflammatory response in brain tissue alongside the microstructural alteration. The administration of CV with nicotine in EAC-bearing mice rescued the detrimental effects of nicotine. Conclusions: CV aids in reducing the harmful effects of nicotine and returns the conditions caused by nicotine to near-control levels. Thus, we are in favor of giving it to cancer patients who are taking daily dosages of nicotine even by smoking cigarettes or being exposed to second-hand smoke

<i>Boswellia serrata</i> Resin Extract in Diets of Nile Tilapia, <i>Oreochromis niloticus</i>: Effects on the Growth, Health, Immune Response, and Disease Resistance to <i>Staphylococcus aureus</i>

The influences of Boswellia serrata resin extract (BSRE) as a feed additive on the growth performance, immune response, antioxidant status, and disease resistance of Nile tilapia, Oreochromis niloticus L. were assessed. One hundred-forty four fingerlings (initial weight: 21.82 ± 0.48 g) were randomly allotted into four groups with three replicates where they were fed on one of four treatments with four levels of Boswellia serrata resin extract 0, 5, 10, or 15 g kg−1, BSRE0, BSRE5, BSRE10, BSRE15, respectively for eight weeks. After the end of the feeding trial, the fish were challenged with Staphylococcus aureus, and mortalities were noted. The final body weight, total body weight gain, and the total feed intake were quadratically increased in BSRE5 treatment (p p p p p p S. aureus challenged fish. The histoarchitecture of the gills and kidney was normal in the BSRE5 treatment and moderately changed in BSRE10 and BSRE15 treatments. The splenic lymphoid elements were more prevalent, and the melano-macrophage centers (MMC) were mild to somewhat activated in BSRE supplemented treatments. Dietary BSRE supplementation improved the intestinal histomorphology. It can be concluded that BSRE addition can enhance the antioxidant activity, immune status, and disease resistance of O. niloticus to S. aureus infection. The level of 5 g kg−1 BSRE can improve fish growth without causing harmful effects on fish health. The highest levels of BSRE are not recommended as they badly affected the histoarchitecture of many vital organs

Application of Gurma Melon <i>(Citrullus lantus var. colocynthoides)</i> Pulp-Based Gel Fat Replacer in Mayonnaise

Gurma melon pulp-based gel (GMPG) was examined as a fat replacement in mayonnaise. GMPG was used to partially replace fat in quantities of 25, 50, and 70%, abbreviated as GMPG-25, GMPG-50, and GMPG-70, respectively. Mayonnaise’s physicochemical and sensory properties were studied. The data demonstrated that all low-fat mayonnaises had much lower energy value but significantly higher water content than their full-fat equivalents and that these differences developed as GMPG replacement levels increased. A microstructure analysis revealed compact the packing structures of big droplets in the whole fat sample and a baggy structure network of aggregated tiny droplets in the GMPG-25, GMPG-50, and GMPG-70 samples. There were no significant differences in pH or water activity after one day of storage between the full-fat and low-fat mayonnaises. Mayonnaises with GMPG-50 and GMPG-70 exhibited the same hardness as full-fat, whereas mayonnaises with GMPG-25 were harder than the other samples. Increased mayonnaise whiteness (L* increase and a* and b* reduction) was seen with reductions in fat. All samples had good sensory approval, with the 50% oil mayonnaise appearing to be the most appealing. It has been demonstrated that GMPG is an effective fat replacement agent