Abstract Plant protein ingredients are increasingly included in mullet feeds and are expected to be contaminated with mycotoxins (AFB1). Thus, this study investigated the protective role of Saccharomyces cerevisiae against oxidative stress and hepato-renal malfunction induced by AFB1 contamination in mullets. Four diets were formulated, where the first was kept as the control diet, and the second was supplemented with S. cerevisiae at 5 × 106 cells/g. The third diet was supplied with AFB1 at 1 mg/kg, and the fourth was supplemented with S. cerevisiae and AFB1. Mullet fed the control or both AFB1 and S. cerevisiae (yeast/ AFB1) had similar FBW, WG, SGR, and FCR (P˃0.05). Mullet treated with S. cerevisiae without AFB1 contamination showed the highest FBW, WG, and SGR (P<0.05), while fish in the AFB1 group had lower FBW, WG, and SGR and higher FCR than fish in the control and yeast/ AFB1 groups (P<0.05). Using yeast with AFB1 prevented pathological hazards and improved intestinal structure. Further, yeast combined with AFB1 reduced the degenerative changes and enhanced the histological structure except for a mild inflammatory reaction around the bile duct. Fish in the control or yeast/ AFB1 group had higher HB, PCV, RBCs, and WBCs than fish in the AFB1 group (P<0.05). Fish fed the control, or the yeast/ AFB1 diets had similar total protein and albumin levels with higher values than fish contaminated with AFB1 (P<0.05). Fish fed the control and yeast/ AFB1 diets had similar ALT, AST, urea, and creatinine levels (P˃0.05) and were lower than fish contaminated with AFB1. Additionally, fish fed the control and yeast/ AFB1 diets had similar CAT, GPx, SOD, and MDA (P˃0.05) and were lower than fish contaminated with AFB1 (P<0.05). In conclusion, incorporating S. cerevisiae ameliorated the negative impacts of AFB1 toxicity on mullets’ growth, hepato-renal function, and antioxidative capacity.

The reaction between different arylhydrazones and ninhydrin (= indene-1,2-3-trione) in acetonitrile at room temperature is described to produce novel bioactive 1-(3-chlorophenyl)indeno[1,2-c]pyrazol-4(1H)-one analouges. In evaluations of the ability to inhibit the growth of different human cell lines and some pathogenic bacterial strains in vitro, compounds 3c and 3f showed significant potency compared with the reference drugs. Both derivatives interacted well with the active site of the BRAF protein, according to molecular docking studies.

Mycotoxicosis is a severe challenge in the aquafeed industry and is involved in low productivity and high economic loss. On this occasion, available dietary supplements, including probiotics, may relieve the impacts of mycotoxicosis on the performances of aquatic animals. In this study, four test diets were prepared to test the effects of Bacillus subtilis (BS), ochratoxin A (OTA), and their mixture (BS/OTA) on the performances of Mullet (Liza ramada). Fish of similar initial weight (11.38 ± 0.24 g) were divided into four groups stocked in triplicate hapas (0.5 ×0.5 ×1 m) at 15 fish per hapa. Fish fed the control diet (without BS or OTA), BS (2 × 106 CFU/g), OTA (1 mg/kg) or BS (2 × 106 CFU/g) and OTA (1 mg/kg) (BS/OTA). After eight weeks, the final weight (FBW) and specific growth rate (SGR) were markedly enhanced by dietary BS and reduced by OTA contamination, while the feed conversion ratio (FCR) was meaningfully reduced by dietary BS and increased by OTA. The hemoglobin (Hb), packed cell volume (PCV), red blood cells (RBCs), and white blood cells (WBCs) were markedly lowered by OTA toxicity. Fish fed BS, or BS/OTA diets showed no significant differences with the control in terms of Hb, PCV, RBCs, and WBCs (p ˃ 0.05). The BS-fed fish showed the same normal intestinal and liver structure with an improved appearance of intestinal villi. The OTA-exposed fish showed deterioration of intestinal mucosa and stunted growth of intestinal villi with severe liver vascular dilatation and congestion in addition to hepatocytes degeneration. The combination of BS with OTA alleviated the pathological effect of individual OTA on the intestinal villi, improved intestinal morphology, and restored the normal hepatic structures with mild periductal inflammatory reaction around the bile duct. The blood total protein and albumin levels were markedly increased by dietary BS and lowered by OTA. Fish fed BS/OTA diet had higher alanine aminotransferase (ALT), aspartate aminotransferase (AST), and urea than fish fed the control but lower than those contaminated with OTA. The catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were markedly increased by dietary BS and lowered by OTA toxicity. However, the malondialdehyde (MDA) level was decreased by dietary BS and increased by OTA toxicity. Interestingly, fish fed the control and BS/OTA diet had similar FBW, SGR, FCR, survival rates, Hb, PCV, RBCs, WBCs, creatinine, CAT, GPx, SOD, and MDA levels. In conclusion, dietary B. subtilis relieved the negative impacts of OTA contamination via protecting fish's intestine, liver, and kidney function.

The use of disinfectants has drastically increased in response to the growing public awareness of risks of microbial infection. However, this practice has a negative impact on the environment as it results in dumping large volumes of antimicrobial and microbicidal compounds in aquatic and terrestrial ecosystems. Chloroxylenol (PCMX) is a phenolic compound that poses public health and environmental risks art high concentrations. Here, a novel disinfectant was proposed to increase the lethality of PCMX by adding copper (Cu) to it. However, it was necessary to demonstrate that this mixture is fungicidal and not merely fungistatic, and that the addition of Cu does, in fact, increase PCMX lethality. We evaluated the fungicidal efficacy of PCMX/Cu on Candida albicans. PCMX/Cu synergy was explored on biofilm formation, biochemistry, and morphology of C. albicans. Inhibition increased with PCMX increased concentration. The combination of Cu and PCMX disrupted fungal ultrastructure, biofilm formation, and biochemical characteristic.

Polyol esters materials, which have been developed from ethylene glycol, glycerol, pentaerythritol and sorbitol with rosin, were investigated for their formed films and coating properties. Films were dried and characterized for chemical and mechanical resistances. Their films were highly resistant to water, solvents (acetone, toluene and methanol), and acids (10% hydrochloric acid and 20% sulfuric acid) and poorly resistant to alkali (10% sodium hydroxide) as well as adhesion, tensile strength, elongation test, modulus of elasticity, pinhole test and scratching and flexibility tests. Incorporation of ethylene glycol, glycerol, pentaerythritol and sorbitol with rosin was done to achieve good mechanical characteristics and high chemical resistance to these films. The prepared compounds were tested for antibacterial activity against Trametes versicolor and Gloeophyllum trabeum.

AS of late a great deal of studies have been led to distinguish regular mixes for counteractive action of the advancement and repeat of malignant growths. The present investigation went for investigating the auxiliary metabolites substance of Pistacia atlantica Desf. (Anacardiaceae) leaves extracts and surveying their cytotoxic activity towards some malignant growth cell lines. In addition, the defensive impact of aqueous methanol and ethyl acetate extracts towards the CCl4 induced hepatotoxicity in rodents was explored. Novel components isolation was done utilizing customary chromatographic systems. The structures of the novel components were clarified dependent on the UV, NMR spectral data information alongside their mass-spectrometric investigations. The ethyl acetate extract of P. atlantica leaves contains a complicated mixture of phenolic acids and gallotannines, were elucidated for the first time from this plant, including polyphenolic acid; ellagic acid (1); 3,3'- dimethoxyellagicacid (2) and gallotannines, namely: 1,2,3,4,6-penta-Ogalloyl-beta-4C1-glucopyranose (3); 1,6-digalloylglucopyranose (4);1,3-digalloyl glucopyranose (5); 2,3-digalloyl-glucopyranose,nilocitin (6);2,3,6-trigalloylglucopyranose (7) and 2,3-di-O-galloyl-4,6-O-hexahydroxydiphenoyl-(alpha/beta)-4C1-glucopyranose, (8). The identification of isolated compounds by conventional methods, spectroscopic analysis, including 1D-NMR, 2D-NMR, ESIMS and HRESI mass as well. The search for novel, potentially biologically active extract becomes much more efficient after identification of all compounds in that mixture. In vitro cytotoxic activity of methanol and ethyl acetate extracts of Pistacia atlantica and resulted new compounds on four human cancer cell lines to be specific: Colorectal adenocarcinoma cell line (Caco-2 cell line), Prostate carcinoma cell line (PC3 cell line), hepatocellular carcinoma (HEPG2), Caucasian bosom adenocarcinoma (MCF-7). SRB assay was used to measure the potential cytotoxicity. The ethyl acetate extract showed a higher cytotoxicity to Caco-2 cell line with IC50 = 3.38 mu g/ml and PC3 cell line with IC50=14.3 mu g/ml. Furthermore, the methanol extract was least cytotoxic to normal cell lines. The strong cytotoxic potential was observed in pure compound pentagalloyl glucopyranose (3) to all three cancer cell lines (HEPG2, Caco-2, MCF-7), IC50 of HEPG2 value = 4.5 mu g/ml. the IC50 for Caco-2 was 11 mu g/ml. and MCF7, IC50=13.5 mu g/ml. as well, in comparison with pure compounds (4,7,8). The growth inhibition of 50% (IC50) for each extract was calculated from the optical density of treated and untreated cells. Moreover, methanol and ethyl acetate extracts of Pistacia atlantica resulted in an attractive candidates for ameliorating of hepatotoxicity induced by CCl4 in rats through scavenging free radicals, improved liver functions, and normalizing the liver histopathological architecture.

Many SNPs in the Prothrombin gene were known to be of clinical significance and associated with variety of clinical states. Molecular composition of F2 gene variants could help in studying genotypic phenotypic relationship. We used computational methods to analyze F2 gene variants and predict the disease associated variants either due structural variation or expression dysregulation.F2 gene contain 2938 SNPs in Homo sapiens, 202 missense, 5 nonsynonymous, 118 synonymous, 21 in the 3'UTR and 10 in the 5'UTR. There were two SNPs In the 3'UTR with three different alleles two of them disrupts the miRNA binding site while the third one creates new miRNA binding sites. Of the missense SNPs 17.3% (35/202) were damaging by both SIFT and Polyphen-2. The SNPs then analyzed by I-Mutant 100% (35/35) of them found to be change protein stability, of which 65.7% (23/35) were disease related variants according to PHD-SNP. Damaging SNPs were then presented to Project HOPE for further functional analysis and Structural modeling. Our work proposes twelve most deleterious SNPs to be associated with Prothrombin gene disease affecting human health, SNP ID (rs121918484, rs147456134, rs150569436, rs121918482, rs139552841, rs121918478, rs377462682, rs202003146, rs121918480, rs142495261, rs201577861, rs188001809).

Aim: To assess clinically, radiographically and laboratory the antimicrobial effect of propolis, miswak, green tea, sodium hypochlorite and chlorhexidine on necrotic teeth with apical peridontitis. Materials and Methods: A total of 50 patients with chronic apical periodontitis in a permanent mature single–rooted tooth with a necrotic pulp were included. Root canals were instrumented using Revo S NiTi files and different irrigants: Sodium hypochlorite 3% (NaOCl), 2% chlorhexidine (CHX), 20% ethanolic extract of Egyptian propolis, 20% ethanolic extract of Miswak and 20% ethanolic extract of Green tea. Root canals were sampled before (S1) and immediately after the chemomechanical preparation (S2). The samples (S1&S2) were transferred for culturing and incubation (both aerobically and anaerobically). The patients were re-evaluated both clinically and radiographically after 1, 3 and 6 months). Results: CHX group showed the highest mean % reduction in Log10 of anaerobic bacterial counts (95.5±8.0). CHX group showed non-statistically significant difference from NaOCl (86.2±16.7) and Propolis (84.4±9.7). Miswak group showed statistically significantly lower mean % reduction (75.6±19.1) than CHX group and NaOCl group, but non-statistically significant difference from Propolis group. Green tea group showed the lowest statistically significant mean % reduction in Log10 of anaerobic bacterial counts (50.10±10.35). Conclusion: Propolis, Salvadora Perisca and green tea alcoholic extracts at 20% concentration showed considerable antimicrobial effect against chronic apical periodontitis microbes generally and E. faecalis definitely.

Soluble Curcumin: A Promising Oral Supplement For Health ManagementPuneet Gandhi, Zeba Khan, Nivedita Chakraverty

Furocoumarins and their related compounds are a plentiful source for drugs that are candidates in relation to their safety and efficiency. The present investigation is concerned with the synthesis, chemical study and characterization of new furocoumarin derivatives with the objective of discovering novel and potent anticancer agents. This challenging goal prompted us to diversify the reactions in order to obtain end products with different functional groups. Friedel-Craft , s acetylation of I,II,III,IV,V and VI namely Xanthotoxin, 4-methoxy-5hydroxyl psoralen, 4,5-dimethoxy psoralen, 4,9-dimethoxy-5-hydroxy psoralen, 4,5,9-trimethoxy psoralen, and imperatorin yielded the acetyl compounds (VII, VIII, IX, X, XI,XII, XIII and XIV) respectively. Aldol condensation of (VII) with aromatic and/ or hetero aldehydes formed chalcones (XV) and (XVI). Bromination of xanthotoxin I in acetic acid yielded the bromo derivative (XVII), which reacted with alkaline dimethyl sulfate, aluminum chloride, acetic anhydride, hydrazine hydrate, malononitrile, ethyl cyanoacetate and sodium ethoxide to give (XVIII, XIX, XX, XXI, XXII, XXIII and XXIV) respectively. The bromo acrylic acid benzofuran (XXIV) reacted with malononitrile and or ethyl cyanoacetateto to give (XXII) and (XXIII) respectively. The Structures of the synthesized compounds were established on the basis of elemental analysis, IR, 1 H NMR, Mass and spectral data. The anticancer activity of some of the synthesized compounds was evaluated against liver cancer cell lines HEPG2 that induced a moderate growth inhibition in a dose-dependent manner World Journal of Pharmaceutical Research SJIF Impact Factor 5.990 Volume 4, Issue 7, 1794-1818. Research Article ISSN 2277– 7105

A series of novel 2,7-dimethyl-1,8-naphthyridine derivatives substituted with Mannich bases 2a–d, N-β-glycosides 6a–e, 7a–e, Schiff’s bases 8a–c, pyrazolone 9, and S-alkylated derivatives 10a–c have been synthesized in good yields starting from 4-hydroxy-2,7-dimethyl-1,8-naphthyridine 1 through multi-step synthesis. The newly synthesized title compounds were evaluated for their HepG2 cell growth inhibition, the results revealed that all the tested compounds process inhibitory effects on the growth of HepG2 liver cancer cells. Compound 8b showed the highest inhibition activity against HepG2 cell line (IC50 equals 3.2 μg/mL) among all tested compounds. The results were compared to 5-Fluorouracil (5-FU) and doxorubicin as reference drugs, (IC50 5 and 3.56 μg/mL). Furthermore, molecular docking of compounds 3b, 6a, and 8b into the binding site of topoisomerase II was carried out. The results of the binding energy scores of these compounds were compared to the docking score of Vosaroxin, a known 1,8-naphthyridine derivative which is in clinical trials as potential anticancer drug. Compound 8b docking result revealed that it is the only tested compound that intercalate with DNA segment of the topoisomerase II, similar to Vosaroxin which was used as reference drug for docking comparison.

Appendicectomy for appendicitis is one of the commonest surgical procedures performed worldwide. The residual appendiceal stump left after an initial appendectomy risks the development of stump appendicitis. Stump appendicitis is a real recognized entity but not often considered when evaluating patients with right lower quadrant abdominal pain, especially those with past history of appendectomy. It remains a clinical challenge with the result that its diagnosis and effective treatment are often delayed with possible attendant morbidity or mortality. Stump appendicitis results from obstruction of the lumen of the remaining appendix stump, usually by a faecolith. This increases intraluminal pressure, impairing venous drainage and allowing subsequent bacterial infection. We present the case of a twenty-five (25)-year-old female who underwent laparoscopic appendicectomy and presented four and half (4(1/2)) months later with fever, right lower quadrant abdominal pain, and tenderness associated with repeated vomiting. Exploratory laparotomy was carried out after clinical and imaging studies which revealed big inflammatory mass with abscess at the right iliac fossa and recurrent appendicitis of the appendiceal stump. Surgical treatment is easy but recognition of this important entity but potentially dangerous condition should always be borne in mind in order to avoid delay in its diagnosis and treatment.

6-Amino-2-thiouracil ( 1 ) was condensed with benzenesulfonyl chloride and p -toluenesulfonyl chloride in presence of pyridine as an acid binder to give sulfonamides 2a , b , which could be methylated in basic medium to give methylmercapto derivatives 3a , b , which in turn reacted with bromine in glacial acetic acid to yield 5-bromo derivatives 4a , b . On the other hand, compounds 2a , b were cyclocondensed with monochloroacetyl chloride, p -tolualdehyde in glacial acetic acid/pyridine, and ethyl bromoacetate to give the corresponding thiazolopyrimidines 5a , b , 6a , b , and 7a , b , respectively; also compounds 2a , b were hydrazinolyzed to compounds 8a , b , which could be cyclized to triazolopyrimidines 9a , b in presence of formic acid. They could also be condensed with p -anisaldehyde to give hydrazones 10a , b . In another pathway, compounds 2a , b were reacted with monochloroacetic acid in basic medium to give acetic acid derivatives 11a , b . It can be deduced from the preliminary screening results that the cell lines most sensitive to the antiproliferative activity of tested compounds are human liver HEPG2 and colon cancer HT-29. All selected compounds exhibited moderate to strong growth inhibition activity against the HEPG2 cell line with 50 % inhibitory concentration (IC 50 ) ranging between 1 and 10 μg/ml. The most active compounds, which revealed antiproliferative activity also against human colon HT-29 and breast MCF-7 cell lines, were 3a , 3b , 4a , and 10a .

The present work deals with the development of a new slow release polymeric material, based on maize starch/cellulose acetate blend polymerized with acrylic acid monomer by free-radical mechanism. The polymerization was initiated by a redox system. The synthesized polymeric material may be used as a carrier for some active compounds such as anticancer drugs and has been characterized by Fourier transform spectroscopy. The active compounds are a new series of heterocyclic derivatives that had an anticancer effect and were prepared from pyrimidine and coumarin compounds, namely: 7-(2-methoxyphenyl)-5-thioxo-5,6-dihydro[1,2,4]triazolo[4,3-c] pyrimidine-8-carbonitrile (compound I), 8-(2-methoxyphenyl)-3,4-dioxo-6-thioxo-3,4,6,7-tetrahydro-2h-pyrimido[6,1-c]-[1,2,4]triazine-9-carbonitrile (compound II), and 4-substituted-1-(1-(7-methoxy-4-methyl-coumarin-8-yl) ethylidene) thiosemi-carbazide (compound III). They were incorporated into the prepared polymer matrix. The polymer-carried drug was tested for slow release drug delivery through testing it in aqueous media for different time periods and examining it as an anti-proliferative agent against human liver cancer cell line (HEPG2). The release rate of the drug was evaluated in aqueous media at different pHs as well as in dimethyl formamide which is the good solvent of such drugs. The release was measured spectrophotometrically. It was found that the release rate depends on the pH of the aqueous media. The release of the drug in the alkaline media was found to be high compared with other media. Also, the sustained release of the drug was extended to about 20 days. The activity of the released drug against human liver cancer cell line was tested. The results showed that compound (III) gave the highest growth inhibition activity followed by compound (II), while compound (I) indicated the lowest activity against the human liver (HEPG2) cancer cell line.

Starting from the reaction of ethyl cyanoacetate with thiourea and the appropriate aldehydes, a series of new thiopyrimidine derivatives were prepared. Antibacterial evaluation results revealed that compounds 12b, 4c and 11b gave the highest antibacterial activity against all tested bacterial strains. Also, some of the novel compounds were evaluated as cytotoxic agents against liver cancer (HEPG2) cell line. It was noticed that some of the derivatives induced significant growth inhibition with IC50 values (ranged from 6.35 to 9.38 μg/mL) in comparison to 5-Fluorouracil after treatment (IC50: 5 μg/mL).

Praziquantel, 2-(cyclohexylcarbonyl)-1,2,3,6,7,11b-hexahydro-4 H -pyrazino[2,1- a ]isoquinolin-4-one, was used as the parent starting material to synthesize a new series of praziquantel-3-arylidene derivatives 1a–c and praziquantel–Mannich bases 2a–d , hoping to obtain new antischistosomal compounds of more activity and lower adverse effects. The antischistosomal activity of the newly synthesized compounds was evaluated using in vitro Schistosoma mansoni worm killing tests. Both compounds 2c and 2d exhibited significant in vitro antischistosomal activity and may offer promising use as an antischistosomal drug either alone or in combination with praziquantel.

Starting from the reaction of ethyl cyanoacetate with thiourea and the appropriate aldehydes, a series of new pyrimidine derivatives were prepared. Ten selected pyrimidine derivatives were subjected to a screening system for the investigation of their antitumor potency against liver (HEPG2) cell line. The antitumor activity results indicated that most of the selected pyrimidine derivatives showed moderate growth inhibition activity against the tested cell line, but with varying intensities in comparison to the known anticancer drugs: 5-fluorouracil and doxorubicin. Some of the synthesized compounds were also tested for their antimicrobial activity against bacteria as well as fungal isolates.

2-Hydrazino-3-chloroquinoxaline 2 was prepared and reacted with active methylene compounds, potassium thiocyanate, carbon disulfide, phenylisothiocyanate, acetic acid, ethyl chloroformate, triethyl orthoformate, and Lawessen's reagent (LR) to give a new class of fused quinoxalines 4-16, respectively. Also, 2,3-dihydrazinoquinoxaline 3 was prepared and reacted with carbon disulfide, phenyl isothiocyanate, and triethyl orthoformate to give the corresponding di[1,2,4] triazolo-[4,3-a:3',4'-c]-quinoxalines 17-19, respectively. Reaction of 3 with LR gave the corresponding di[1,2,4,3]triazophospholo[4,5-a:5',4'-c] quinoxaline-1,6-dithione (20). It was found that all synthesized compounds exhibit antimicrobial activity and that compound 20 had a broad spectrum of activity.