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Sobhi M Gomha,1,2 Hyam A Abdelhady,2 Doaa ZH Hassain,2 Aboubakr H Abdelmonsef,3 Mohamed El-Naggar,4 Mahmoud M Elaasser,5 Huda K Mahmoud2 1Chemistry Department, Faculty of Science, Islamic University in Almadinah Almonawara, Almadinah Almonawara, 42351, Saudi Arabia; 2Chemistry Department, Faculty of Science, University of Cairo, Giza, Egypt; 3Chemistry Department, Faculty of Science, South Valley University, Qena, 83523, Egypt; 4Chemistry Department, Faculty of Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates; 5The Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo, 11371, EgyptCorrespondence: Sobhi M Gomha Email s.m.gomha@gmail.comAboubakr H Abdelmonsef Email aboubakr.ahmed@sci.svu.edu.egIntroduction: Hybrid drug design has developed as a prime method for the development of novel anticancer therapies that can theoretically solve much of the pharmacokinetic disadvantages of traditional anticancer drugs. Thus a number of studies have indicated that thiazole-thiophene hybrids and their bis derivatives have important anticancer activity. Mammalian Rab7b protein is a member of the Rab GTPase protein family that controls the trafficking from endosomes to the TGN. Alteration in the Rab7b expression is implicated in differentiation of malignant cells, causing cancer.Methods: 1-(4-Methyl-2-(2-(1-(thiophen-2-yl) ethylidene) hydrazinyl) thiazol-5-yl) ethanone was used as building block for synthesis of novel series of 5-(1-(2-(thiazol-2-yl) hydrazono) ethyl) thiazole derivatives. The bioactivities of the synthesized compounds were evaluated with respect to their antitumor activities against MCF-7 tumor cells using MTT assay. Computer-aided docking protocol was performed to study the possible molecular interactions between the newly synthetic thiazole compounds and the active binding site of the target protein Rab7b. Moreover, the in silico prediction of adsorption, distribution, metabolism, excretion (ADME) and toxicity (T) properties of synthesized compounds were carried out using admetSAR tool.Results: The results obtained showed that derivatives 9 and 11b have promising activity (IC50 = 14.6 ± 0.8 and 28.3 ± 1.5 μM, respectively) compared to Cisplatin (IC50 = 13.6 ± 0.9 μM). The molecular docking analysis reveals that the synthesized compounds are predicted to be fit into the binding site of the target Rab7b. In summary, the synthetic thiazole compounds 1– 17 could be used as potent inhibitors as anticancer drugs.Conclusion: Promising anticancer activity of compounds 9 and 11 compared with cisplatin reference drug suggests that these ligands may contribute as lead compounds in search of new anticancer agents to combat chemo-resistance.Keywords: thiazoles, hydrazones, hydrazonoyl halides, docking, Rab7b, MCF-7

HLA alleles are representative of ethnicities and may play important roles in predisposition to hematological disorders. We analyzed DNA samples for HLA-A, -B, -C, -DRB1, and -DQB1 loci, from 1550 patients and 4450 potential related donors by PCR-SSO (Polymerase chain reaction sequence-specific oligonucleotides) and estimated allele frequencies in donors and patients from 1550 families who underwent bone marrow transplantation (BMT) in Egypt. We also studied the association between HLA allele frequencies and incidence of acute myeloid leukemia, acute lymphoblastic leukemia, and severe aplastic anemia. The most frequently observed HLA class I alleles were HLA- A*01:01 (16.9%), A*02:01 (16.1%), B*41:01 (8.7%), B*49:01 (7.3%), C*06:02 (25.1%), and C*07:01 (25.1%), and the most frequently observed class II alleles were HLA-DRB1*11:01 (11.8%), DRB1*03:01 (11.6%), DQB1*03:01 (27.5%), and DQB1*05:01 (18.9%). The most frequently observed haplotypes were A*33:01~B*14:02 ~ DRB1*01:02 (2.35%) and A*01:01~B*52:01~DRB1*15:01 (2.11%). HLA-DRB1*07:01 was associated with higher AML odds (OR, 1.26; 95% CI, 1.02-1.55; p = 0.030). Only HLA-B38 antigen showed a trend towards increased odds of ALL (OR, 1.52; 95% CI, 1.00-2.30; p = 0.049) HLA-A*02:01, -B*14:02, and -DRB1*15:01 were associated with higher odds of SAA (A*02:01: OR, 1.35; 95% CI, 1.07-1.70; p = 0.010; B*14:02: OR, 1.43; 95% CI, 1.06-1.93; p = 0.020; DRB1*15:01: OR, 1.32; 95% CI, 1.07-1.64; p = 0.011). This study provides estimates of HLA allele and haplotype frequencies and their association with hematological disorders in an Egyptian population., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The reaction of sulfamethoxazolehydrazonoyl chloride with thiosemicarbazones, bis-thiosemicarbazones, or 4-amino-3-mercapto-1,2,4-triazole in dioxane in the presence of triethylamine as a basic catalyst at reflux resulted in the regioselective synthesis of thiazoles and bis-thiazoles linked to azo-sulfamethoxazole as novel hybrid molecules. The structures of the new compounds were confirmed using a range of spectra. Each compound's antibacterial properties were evaluated using the agar well-diffusion technique, and most of them demonstrated significant potency. In silico investigations revealed that the described compounds had strong interactions with the binding sites of MurE ligase, tyrosyl-tRNA synthetase, and dihydropteroate synthase, demonstrating inhibitory activity., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

A total of 150 adult quails, aged 8 wk, were divided into 5 groups to study the effect of sumac seed powder on reproductive and productive parameters, egg quality, digestive enzymes, and quail breeders' blood profiles. Dietary supplements containing sumac powder were formulated as follows: group 1 (G1) (control, only basal diet); group 2 (G2) (basal diet + 1 g sumac powder/kg diet); group 3 (G3) (basal diet + 2 g sumac powder/kg diet); group 4 (G4) (basal diet + 3 g sumac powder/kg diet); and group 5 (G5) (basal diet + 4 g sumac powder/kg diet). The feed conversion ratio was significantly higher at all levels of sumac powder (P < 0.05) compared to the control group (G1). Overall, during the study (8-16 wk), quail-fed 3 g sumac powder/kg diet (G4) showed no significant increase (P > 0.05) in the feed intake compared to the control group. Sumac powder supplementation significantly (P < 0.05) increased egg number, egg weight, egg mass, fertility, and hatchability. While supplementing with sumac powder did not impact other egg quality parameters, it did significantly (P < 0.05) increase yolk percentage, Haugh unit, and unit surface shell weight. Furthermore, when compared to the control group (G1), birds given 2, 3, or 4 g of sumac powder/kg diet showed a significant improvement (P < 0.05) in hematological parameters such as red blood cells, white blood cells, and hemoglobin, as well as a decrease in glucose levels. Feeding quail with a 3 g sumac powder/kg diet (G4) resulted in significantly (P < 0.05) higher globulin levels and improved albumin/globulin ratio compared to other treatments and control (G1). Sumac powder intake significantly (P < 0.05) reduced plasma lipid profile, liver enzymes (aspartate aminotransferase, and alanine aminotransferase), and kidney functions (creatinine, and urea). Furthermore, the supplementation of sumac powder resulted in a substantial increase (P < 0.05) in the levels of amylase, lipase, and protease. Sumac powder administration also significantly (P < 0.05) improves immunity by boosting IgM, IgG, IgA, and lysozyme levels in quail breeders' plasma. Supplementing with sumac powder, on the other hand, increased levels of reduced glutathione, total antioxidant capacity, catalase, and superoxide dismutase. The results of the current study indicated that the addition of 1, 2, 3, and 4 g of sumac powder to the diet of Japanese quail breeders led to improvements in egg quality, digestive enzymes, reproductive and productive performances, and most blood hematological and biochemical parameters., Competing Interests: DISCLOSURES The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The development of antibiotic-resistant microorganisms prompted the investigation of possible antibiotic substitutes. As a result, the purpose of the current study is to assess the effect of dietary Spirulina platensis extract as an antibiotic alternative on Japanese quail (Coturnix japonica) growth, antioxidant status, blood parameters, and cecal microorganisms. There was a total of 150 Japanese quails used in this study, divided equally among 5 experimental groups (10 birds per group with 3 replicates): group 1 (G1) received a basal diet without any S. platensis extract, group 2 (G2) received a basal diet supplemented with 1 mL S. platensis extract/kg, group 3 (G3) received a basal diet supplemented with 2 mL S. platensis extract/kg, group 4 (G4) received a basal diet supplemented with 3 mL S. platensis extract/kg, and group 5 (G5) received a basal diet supplemented with 4 mL S. platensis extract/kg from d 7 until d 35. The results showed that compared to the control birds in G1, Japanese quail supplemented with 4 mL of S. platensis extract/kg of diet (G5) had significantly better live body weight, body weight gain, feed intake, feed conversion ratio, digestive enzymes, blood parameters, liver and kidney functions, lipid profile, antioxidant profile, immunological parameters, and cecal microorganism's count. There were no significant changes in the percentage of carcasses, liver, and total giblets among all the 5 groups. Only gizzard percentage showed a significant increase in G2 compared to birds in G1. In addition, intestinal pH showed a significant drop in G2 and G5 compared to birds in G1. After cooking the quail meat, the juiciness and tenderness increased as S. platensis extract levels increased, whereas aroma and taste declined slightly as S. platensis extract levels increased. Furthermore, when a high concentration of S. platensis extract was used, the lightness of the meat reduced while its redness and yellowness increased. The disk diffusion assay showed that S. platensis extract had significant antibacterial activity against Staphylococcus aureus, Listeria monocytogenes, Campylobacter jejuni, and Salmonella typhi, with inhibition zones ranging from 16 to 42 mm. This activity may be attributable to the volatile chemicals in S. platensis extract, of which Geosmin and 2-methylisoborneol are the primary components. In the diet of Japanese quails, it is possible to draw the conclusion that the extract of S. platensis can be utilized as a feed additive and as an alternative to antibiotics., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Parenting a child with autism represents an extraordinary challenge for families, resulting in prominent levels of stress and burden that subsequently affect their expressed emotions. This study aimed to evaluate the effect of counseling intervention on stress and expressed emotions among family caregivers of children with autism. The research used a pre-post interventional design, to evaluate 40 family caregivers of children with autism. The interviewing questionnaire assessed socio-demographic data, expressed emotions, and parenting stress, revealing that 57.5% of the evaluated family caregivers had severe stress pre-counseling, compared to 25% post-counseling intervention. Additionally, 80% of them had elevated levels of expressed emotions pre-counseling, compared to 32.5% during the post-counseling intervention. Most family caregivers of children with autism experienced significant levels of expressed emotions, and over half of them had severe levels of stress. However, these levels decreased following the implementation of the counseling interventions. Furthermore, there were highly statistically significant correlations between the total levels of expressed emotions and total stress levels among family caregivers before and after the implementation of the counseling intervention., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s).)

Background and Objectives: Post-transplant cyclophosphamide (PTCy) has shown promising results with low rates of severe graft-versus-host-disease (GVHD), either alone or combined with conventional immunosuppression (CIS). However, studies comparing PTCy with CIS as a GVHD prophylaxis are scarce. The study aimed to determine the rates of GVHD and survival outcomes for patients undergoing peripheral blood stem cell transplant (PBSCT) from HLA-matched related donors (MRD) receiving PTCy-based GVHD prophylaxis and compare these outcomes with those of patients receiving methotrexate (MTX) and cyclosporine-A (CsA) as a GVHD prophylaxis., Patients and Methods: Seventy-five patients with advanced hematologic malignancies who underwent MRD allogeneic hematopoietic cell transplantation (allo-HCT) were analyzed prospectively. These patients received PTCy and CSA as a GVHD prophylaxis (therapeutic group) and their outcomes were compared with those of 75 retrospectively collected patients who received methotrexate and CsA as a GVHD prophylaxis (historical group) from the same two transplant centers., Results: The median recipient age was significantly lower in the MTX/CsA group at 28 years compared to 34 years in the PTCy/CSA group. Peripheral blood was the only graft source used. All patients had a complete MRD, with two patients having a one-antigen mismatched related donor within the PTCy/CsA group. The 1-year cumulative incidence (CI) of chronic GVHD was 13.4% with PTCy/CsA and 38.6% with MTX/CsA (P = .001). Acute GVHD CI across all grades did not differ between the groups, with 10.7% for PTCy/CsA and 14.7% for MTX/CsA (P = .46). At two years, the overall survival (OS) (54.4% vs 67.2%, P = 0.282), disease-free survival (DFS) (54.1% vs 66.1%, P = 0.358), relapse rates (27.4% vs 20.1%, P = 0.245), and non-relapse mortality (NRM) (29.3% vs 25%, P = 0.904) did not differ between PTCy/CsA and MTX/CsA, respectively., Conclusion: PTCy-based GVHD prophylaxis in MRD transplant is feasible and leads to lower chronic GVHD rates without causing a significantly different risk of relapse or survival than MTX/CsA. More extensive studies are needed to confirm our results.

Viruses are still the most prevalent infectious pathogens on a worldwide scale, with many of them causing life-threatening illnesses in humans. Influenza viruses, because of their significant morbidity and mortality, continue to pose a major threat to human health. According to WHO statistics, seasonal influenza virus epidemics are predicted to cause over 2 million severe illness cases with high death rates yearly. The whole world has been suffering from the COVID-19 epidemic for two years and is still suffering so far, and the deaths from this virus have exceeded three million cases. Because the great majority of viral infections do not have a specific medication or vaccination, discovering novel medicines remains a vital task. This review covers reports in the patent literature from 1980 to the end of 2021 on the antiviral activities of pyrimidine moieties. The patent database, SciFinder, was used to locate patent applications. A large variety of pyrimidine molecules have been produced and tested for antiviral activity over the last decade. These molecules were reported to inhibit a wide range of viruses, including influenza virus, respiratory syncytial virus, rhinovirus, dengue virus, herpes virus, hepatitis B and C, and human immunodeficiency virus. The cytotoxicity of the developed pyrimidine derivatives was tested in almost all reported studies and the selectivity index was calculated to show the selectivity and safety of such molecules. From the remarkable activity of pyrimidine compounds as antivirals for several dangerous viruses, we expect that these derivatives will be used as potent drugs in the very near future., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This study assessed the restorative dietary effects of Moringa oleifera (MO) leaves extract against the negative impacts of sub-lethal fipronil (FIP) toxicity in Nile tilapia. To achieve this purpose, the growth, body composition, haemato-biochemical measurements, serum immunity, and antioxidant condition of Nile tilapia have been examined. Fish were arranged into 6 experimental groups in quadruplicates. Three groups were fed on diets supplemented with 0.0 (reference group), 1.0 (MO1), and 2.0 (MO2) g kg -1 of MO leaf extract. The other three groups were fed on the same MO levels and concomitantly subjected to a sub-lethal FIP concentration (4.2 µg L -1 for 3 h only per day) and defined as FIP, FIP + MO1, and FIP + MO2. The experiment lasted for 8 weeks. Results unveiled that growth parameters were significantly decreased alongside an increased feed conversion ratio in the FIP-intoxicated group. The moisture and crude protein (%) were decreased significantly together with a significant increase of the crude lipids (%) in the fish body of the FIP group. Sub-lethal FIP toxicity induced hypochromic anemia, leukopenia, hypoproteinemia, hypoalbuminemia, hypoglobulinemia, and hepato-renal failure (increased urea and creatinine concentrations, as well as ALT and AST enzymes). Exposure to sub-lethal FIP also induced (a) immunosuppression manifested by a decline in total IgM, complement C3, and lysozyme activities, (b) enzymatic antioxidant misbalance manifested by decreases in SOD and CAT activities, and (c) oxidative stress (declined T-AOC and elevated of MDA concentrations). On the other side, dietary supplementation with MO leaf extract in FIP + MO1 and FIP + MO2 groups noticeably modulated the aforementioned parameters. Therefore, we can conclude that dietary MO could reduce sub-lethal FIP toxicity in Nile tilapia with a possible recommendation for regular prophylaxis supplementation in Nile tilapia diets., (© 2022. The Author(s).)

Background: Prognostication of AML patients depends on association of genetic and epigenetic abnormalities. We aimed to evaluate the frequency and prognostic significance of Additional Sex comb's Like1 (ASXL1), Isocitrate Dehydrogenase (IDH) and Casitas B- lineage Lymphoma (CBL) mutations in AML assessing their association with different cytogenetic risk category., Methods: We used High Resolution Melting (HRM) technology that detects small differences in PCR amplified sequences by direct melting using EvaGreen saturating dye to analyze epigenetic mutations in 70 denovo AML patients., Results: Median age of AML patients was 39.5 years (18-75). ASXL1, IDH and CBL mutations were detected in 14 (20%), 10 (14%) and 5 (7%) patients, respectively. Mean age of ASXL1 and IDH mutants vs. wild type was 35.9±14.6 years and 42.9±14.4 years (p=0.114) and 46.7±15.2 years vs. 40.6±14.5 years (p=0.290), respectively. AML cytogenetic risk groups included low (25/70, 36%), intermediate (33/70, 47%) and high-risk (12/70, 17%). Nine/14 (64%) ASXL1 and 8/10 (80%) IDH mutants were classified as intermediate risk and 9 ASXL1 positive (64%) were adolescent and young adults (AYA). Overall survival (OS) of mutant ASXL1 vs. wild type was 1.1 years (95% CI 0.83-1.4) vs. 1.9 years (95% CI 0.71-7.51), respectively (p=0.056). OS of mutant IDH vs. wild type was 1.25 years (95% CI 0.85-1.6) vs. 1.8 years (95% CI 1.2-6.7), respectively (p=0.020). In intermediate risk cytogenetic group, ASXL1 and IDH mutants had shorter OS than wild type; 1.1 years (95% CI 0.97-1.2) vs. 2.1 years (95% CI 0.14-10.8) (p=0.002) and 1.8 years (95% CI 0.69-3.15) vs. 2.3 years (95% CI 1.1-5.5) (p=0.05), respectively., Conclusion: ASXL1 and IDH mutations occur at a high incidence among young Egyptian AML patients with intermediate risk cytogenetics and confer a poorer outcome. Integration of mutations into risk profiling may predict outcome and impact therapeutic approach of young AML patient with uncertain prognosis.

Aims: The study aims to synthesize bioactive hybrid pharmacophores (thiazole ring and imidazo[2,1-b]thiazole system) by incorporating them into one biological assessment molecular system., Background: A literature survey revealed that various imidazo[2,1-b]thiazoles, thiazoles, and hydrazones have powerful antimycobacterial activity., Objective: This study demonstrates the effectiveness of molecular hybridization and the scope for imidazo[2,1-b]thiazole-hydrazone-thiazoles to develop as promising antimycobacterial agents., Methods: Several imidazo[2,1-b]thiazole-hydrazine-thiazoles 5a-g, 7a,b, 9a,b, 11a,b, 13, and 15a,b were generated using a molecular hybridization strategy and assessed against Mycobacterium tuberculosis (ATCC 25618) for their in vitro antituberculous activity., Results: Derivative 7b (MIC = 0.98 μg/mL) has shown the most promising antimycobacterial activity among the series tested. Brief structure-activity relationship studies found that the thiazole of chlorophenyl or pyridine, or coumarin had a significant relation with the antimycobacterial activity., Conclusion: The promising antimycobacterial activity of compound 7b compared with the reference drug suggests that this compound may contribute as a lead compound in the search for new potential antimycobacterial agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A 60-day experiment was performed to assess the efficacy of dietary Astragalus membranaceus polysaccharides (ASP) in attenuation of sub-lethal thallium (Tl) toxicity in Nile tilapia. Six experimental groups (in triplicates) were designed where a fish group was raised in clean water and fed basal diet and served as control (CONT), two groups were fed the basal diet supplemented with 0.15% and 0.30% ASP (ASPL and ASPH), Tl-intoxicated group exposed to 1/10 of 96-h LC50 (= 41.9 μg/L), and two other groups were fed 0.15% and 0.30% ASP and concomitantly exposed to 41.9 μg Tl/L (ASPL-Tl and ASPH-Tl). At the end of the experiment, fish behavioral responses, clinical signs, survivability, growth, whole-body composition, intestinal digestive enzymes, serum biochemical parameters, hepatic antioxidative biomarkers, and transcription of stress and apoptosis genes were assessed. Results showed that the whole-body composition, intestinal α-amylase and protease enzymes, serum AST and blood urea levels, and hepatic GSH were not significantly different among groups (P > 0.05). The Tl-intoxicated fish group was off food, had darkened skin, showed restlessness and hyperexcitability, and high mortalities. FBW, WG, SGR and FI were significantly decreased alongside increase FCR in the Tl-exposed group. Tl exposure caused significant increases (P < 0.05) in intestinal lipase enzyme and serum indices such as ALT, creatinine, total cholesterol, triglycerides, glucose, and cortisol levels. Moreover, a significant decreases in hepatic CAT and SOD enzyme activities and significant increases in hepatic MDA contents were also noticed (P < 0.05). Furthermore, Tl exposure induced significant upregulation of hepatic HSP70 and apoptosis-related genes (p53 and caspase 3). Interestingly, dietary supplementation with ASP in ASPL-Tl and ASPH-Tl groups modulated the parameters mentioned above but still not reached the CONT values. Altogether, this study suggests that ASP could be beneficial in the modulation of sub-lethal Tl toxicity effects in Nile tilapia. Additionally, we can conclude that using natural feed supplements such as ASP in aquafeed might be necessary for maintaining the overall health performances of Nile tilapia., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Differential expression of minor histocompatibility antigens between the recipient and donor determines their disparity and can be modified by immunoproteasomes that regulate their processing and presentation. We examined the impact of HA-1 and HA-8 disparity, and immunoproteasome LMP7 polymorphism in 130 pairs. In multivariate analysis, HA-1 disparity showed a statistically significant association with an increased incidence of acute graft-versus-host disease (aGVHD) II-IV (p = 0.043, HR: 3.71, 95%CI = 1.04-13.26), while LMP7-Q/Q showed a trend toward increased incidence of aGVHD compared to LMP7-Q/K and K/K genotypes (p = 0.087, HR: 2.36, 95%CI = 0.88-6.31). All HA-1 and HA-8 disparate patients who developed aGVHD had the LMP7-Q/Q genotype. No significant association could be detected between HA-1, HA-8, or LMP7 and chronic GVHD, relapse-free survival (RFS), overall survival (OS), or transplant-related mortality (TRM). In conclusion, we suggested an association between the HA-1 disparity and the risk of developing aGVHD with a possible modifying effect of LMP7., (Copyright © 2021 Elsevier Inc. All rights reserved.)

This study was conceptualized in order to assess the 96-h LC 50 of bifenthrin (BF) in O. niloticus and also to measure the biochemical, behavioral, and molecular responses of the fish suchronically exposed to a sub-lethal concentration of the insecticide. The role of Petroselinum crispum essential oil (PEO) supplementation in mitigating the resulted neurotoxic insult was also investigated. The acute toxicity study revealed that the 96-h LC 50 of BF is 6.81 μg/L, and varying degrees of behavioral changes were recorded in a dose-dependent manner. The subchronic study revealed reduction of dissolved oxygen and increased ammonia in aquaria of BF-exposed fish. Clinical signs revealed high degree of discomfort and aggressiveness together with reductions in survival rate and body weight gain. The levels of monoamines in brain, and GABA and amino acids in serum were reduced, together with decreased activities of Na + /K + -ATPase and acetylcholine esterases (AchE). The activities of antioxidant enzymes were also diminshed in the brain while oxdative damage and DNA breaks were elevated. Myeloperoxidase (MPO) activity in serum increased with overexpression of the pro-inflammatory cytokines in the brain tissue. BF also upregulated the expression of brain-stress related genes HSP70, Caspase-3 and P53. Supplemention of PEO to BF markedly abrogated the toxic impacts of the insecticide, specially at the high level. These findings demonstrate neuroprotective, antioxidant, genoprotective, anti-inflammatory and antiapoptic effects of PEO in BF-intoxicated fish. Based on these mechanistic insights of PEO, we recommend its use as an invaluable supplement in the fish feed., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Novel 2-indolinone thiazole hybrids were designed and synthesized as VEGFR-2 inhibitors based on sunitinib, an FDA-approved anticancer drug. The proposed structures of the prepared 2-indolinone thiazole hybrids were confirmed based on their spectral data and CHN analyses. The target compounds were screened in vitro for their anti-VEGFR-2 activity. All tested compounds exhibited a potent submicromolar inhibition of VEGFR-2 kinase with IC 50 values ranging from 0.067 to 0.422 μM, relative to sunitinib reference drug (IC 50  = 0.075 ± 0.002 μM). Compounds 5, 15a, 15b, 17, 19c displayed excellent VEGFR-2 inhibitory activity, comparable or nearly equipotent to sunitinib. Compound 13b stood out as the most potent against VEGFR-2 showing IC 50 value of 0.067 ± 0.002 μM, lower than that of sunitinib. In addition, the most potent derivatives were assessed for their anticancer activity against two renal cancer cell lines. Compound 13b (IC 50  = 3.9 ± 0.13 μM) was more potent than sunitinib (IC 50  = 4.93 ± 0.16 μM) against CAKI-1 cell line. Moreover, thiazole 15b displayed excellent anticancer activity against CAKI-1 cell line (IC 50  = 3.31 ± 0.11 μM), superior to that of sunitinib (IC 50  = 4.93 ± 0.16 μM). Thiazole 15b was also equipotent to sunitinib (IC 50  = 1.23 ± 0.04 μM) against A498 cell line. Besides, compound 15b revealed a safety profile much better than that of sunitinib against normal human renal cells. Furthermore, a docking study revealed a proper fitting of the most active compounds into the ATP binding site of VEGFR-2, rationalizing their potent anti-VEGFR-2 activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Three series of nanosized-formazan analogues were synthesized from the reaction of dithiazone with various types of α-haloketones (ester and acetyl substituted hydrazonoyl chlorides and phenacyl bromides) in sodium ethoxide solution. The structure and the crystal size of the new synthesized derivatives were assured based on the spectral analyses, XRD and SEM data. The antibacterial and antifungal activities were evaluated by agar diffusion technique. The results showed mild to moderate antibacterial activities and moderate to potent antifungal activities. Significant antifungal activities were observed for four derivatives 3a, 3d, 5a and 5g on the pathogenic fungal strains; Aspergillus flavus and Candida albicans with inhibition zone ranging from 16 to 20 mm. Molecular docking simulations of the synthesized compounds into leucyl-tRNA synthetase editing domain of Candida albicans suggested that most formazan analogues can fit deeply forming stable complexes in the active site. Furthermore, we utilized the docking approach to examine the potential of these compounds to inhibit SARS-CoV-2 3CLpro. The results were very promising verifying these formazan analogues as a hopeful antiviral agents., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Imidazo[2,1- b ]thiazole scaffolds were reported to possess various pharmaceutical activities., Results: The novel compound named methyl-2-(1-(3-methyl-6-( p -tolyl)imidazo[2,1- b ]thiazol-2-yl)ethylidene)hydrazine-1-carbodithioate 3 acted as a predecessor molecule for the synthesis of new thiadiazole derivatives incorporating imidazo[2,1- b ]thiazole moiety. The reaction of 3 with the appropriate hydrazonoyl halide derivatives 4a - j and 7 - 9 had produced the respective 1,3,4-thiadiazole derivatives 6a - j and 10 - 12 . The chemical composition of all the newly synthesized derivatives were confirmed by their microanalytical and spectral data (FT-IR, mass spectrometry, 1 H-NMR and 13 C-NMR). All the produced novel compounds were screened for their anti-proliferative efficacy on hepatic cancer cell lines (HepG 2 ). In addition, a computational molecular docking study was carried out to determine the ability of the synthesized thiadiazole molecules to interact with active site of the target Glypican-3 protein (GPC-3). Moreover, the physiochemical properties of the synthesized compounds were derived to determine the viability of the compounds as drug candidates for hepatic cancer., Conclusion: All the tested compounds had exhibited good anti-proliferative efficacy against hepatic cancer cell lines. In addition, the molecular docking results showed strong binding interactions of the synthesized compounds with the target GPC-3 protein with lower energy scores. Thus, such novel compounds may act as promising candidates as drugs against hepatocellular carcinoma.

Introduction: Studies addressing the utilization of post-transplant cyclophosphamide (CY) as graft-versus-host disease (GVHD) prophylaxis in allogeneic hemopoietic stem cell transplantation from matched sibling donors are limited and with controversial results. Chronic GVHD incidence necessitating systemic treatment is around 35% in peripheral blood stem cell transplantation (PBSCT) from human leukocyte antigen-matched sibling donors., Patients and Methods: In this study, high-dose CY was added to PBSCT aiming to reduce the incidence of GVHD to reach a lower figure compared with standard GVHD prophylaxis. Fifty-two patients with either benign or malignant hematologic disorders who underwent stem cell transplantation at Nasser Institute Hospital in Egypt from November 2017 to October 2018 were enrolled in this study. Fifty patients had fully human leukocyte antigen-matched siblings, whereas the remaining 2 patients had 1 locus class I mismatched donors. Pre-transplant conditioning regimen was fludarabine and busulfan (FLU/BU) in malignant cases (73.1%) and FLU/CY in benign hematologic disorders (26.9%) and 1 patient with hypocellular myelodysplastic syndrome. For GVHD prophylaxis, CY was given at a dose of 50 mg/kg/day on days 3 and 4 post-transplantation, and cyclosporine (CSA) starting day 5 in 96.1% of patients. For the 1-locus mismatched patients, both CSA and mycophenolate mofetil were administered starting day 5., Results: The 1-year incidence of acute GVHD (aGVHD) was 15.3% and for chronic GVHD (cGVHD) was 13.4%. Historical data of GVHD prophylaxis at our center using CSA and methotrexate showed an incidence of 37% for aGVHD and 33.9% for cGVHD., Conclusions: Post-transplant CY GVHD prophylaxis led to significantly less aGVHD (P = .03) and cGVHD (P = .04)., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The present trial was conducted to evaluate the beneficial role of some feed additives (potassium sorbate; Sor, hydrated sodium calcium almuniosilicate; Hsc and l-methionine; L-M) in attenuating the hepatic and renal toxicity of aflatoxin B1 (AFB1) in rabbits. A total number of 72 NZW growing rabbits (5 week-old) were divided into six experimental groups (four replicates with three rabbits each) as follows: control group, AFB1 group (supplemented with AFB1 0.3 mg/kg diet), AFB1 + Sor group (AFB1 0.3 mg/kg diet + Sor 2 g/kg diet), AFB1 + Hsc group (AFB1 0.3 mg/kg diet + Hsc 5 g/kg diet), AFB1 + L-M group (AFB1 0.3 mg/kg diet + L-M 8 g/kg diet) and AFB1 + Mix group (AFB1 0.3 mg/kg diet + 2 Sor + 5 Hsc + 8 L-M g/kg diet). Serum levels of total protein, albumin and globulin were significantly reduced by AF. AF increased the serum activity of aspartate aminotransferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP) enzymes. While, they were reduced in AF + Sor and AF + Mix groups compared with AF group. AF increased the level of cystatin C and Beta-2 microglobulin (BMG). All other supplements significantly reduced the level of cystatin C than AF; however, this reduction was more pronounced in AF-L-M group. AF + Sor, AF + L-M and AF + Mix equally reduced the BMG level than AF and AF + HSc, however, still higher than control. AF elevated the total cholesterol (TC) and LDL-cholesterol levels. A significant reduction in HDL cholesterol was seen in AF group. Additionally, AF induced pathological alterations in the liver and kidney of exposed rabbits on the other hands, the three additives separately or in mix attenuated the Af-induced alterations. In conclusion, the dietary supplementation of Sor, L-M, Hsc or their mixture was effective in ameliorating the negative effects of AFB1 on liver and kidney function and structure in rabbits with more better improvement obtained by Sor or L-M separately., (© 2020 Blackwell Verlag GmbH.)

Plant-derived additives are used to maintain the health and growth performance of livestock. The use of red pepper oil (RPO) has recently attracted considerable scientific interest mainly due to its potential benefits for animals and humans. The present study was conducted to evaluate the effect of dietary supplementation with RPO on growth performance, carcass measurements, antioxidant status and immunity of growing quails between 1 and 5 weeks of age. A total of 240 growing quails (1-week old) were distributed into 5 equal groups consisting of 48 birds (4 replicates of 12 birds each). The first group was fed a basal diet without RPO (0 g/kg diet), and the second, third, fourth and fifth groups received diets containing RPO (0.4, 0.8, 1.2, 1.6 g/kg diet, respectively). The experiment lasted for 5 weeks. At age of 5 weeks, quails were slaughtered for carcass examinations, microbiological analysis of intestine and to determine blood constituents. Data were statistically analyzed by one-way ANOVA. Quails fed with 0.8 g RPO/kg diet showed 12.14%, 14.4% and 15% improvement in live BW, body weight gain and feed conversion ratio, respectively, compared with the control group. Quails that received diets with 1.2 g RPO consumed more feed than the others during the total period (1 to 5 weeks). Plasma globulin levels were significantly decreased (P = 0.0102), but albumin/globulin ratio was significantly increased (P = 0.0009) in birds fed diets containing RPO (0.4 and 1.2 g/kg) compared with those in the control group. Activity of liver enzymes in the plasma was nonsignificantly decreased in quails supplemented with 0.8 g RPO/kg diet compared with those in the control group. Activities of antioxidant enzymes (glutathione and catalase) in the group fed on diets supplemented with RPO (0.8 g/kg) were significantly higher than those in the control group. The inclusion of RPO (0.8 g/kg diet) in quail diets improved (P < 0.05) plasma lipid profile and also decreased pH of the caecal content (P = 0.0280) compared with those in the control group. The caecal bacterial population, Salmonella spp., coliform and Escherichia coli, were lowered (P < 0.05) in the groups treated with RPO (0.8, 1.2 and 1.6 g/kg) compared with those in the control group. In conclusion, dietary supplementation of RPO (0.8 g/kg) can enhance the performance and antioxidant indices and decrease intestinal pathogens and thus improve the health status of Japanese quail.

Hematopoietic stem cell transplantation (HSCT) is now an established treatment modality with definitive indications for many hematological disorders. However, HSCT requires tremendous resources, and it is increasingly challenging for transplantation experts to practice in the developing world and to reach a compromise between requirements and available resources. Based on 30 years of experience and 4256 transplants (60% allogeneic and 40% autologous), this article focuses on the challenges our HSCT program encountered since it started in 1989 and what opportunities we see to solve them. Since 1997, HSCT procedures increased dramatically with the opening of 15 HSCT units distributed all over Egypt., Competing Interests: Competing interests: The authors declare no conflict of Interest.

Acute graft-versus-host disease (aGVHD) is a severe inflammatory complication of haematopoeitic stem cell transplantation. The nuclear factor- Kappa Beta (NF-κB) signaling pathway regulates T cell activation. The NF-κB controls the expression of microRNA-146a (miR-146a) that in turn regulates NF-κB activation through a negative feedback loop. We aim to analyze the association between NF-κB1 encoding p50 (rs28362491, -94 in.ertion/deletion ATTG) and miR-146a (rs2910164, G > C) polymorphisms and risk of aGVHD. Genotyping was performed for 135 HLA-matched donors using polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP).The incidence of aGVHD grades II-IV was 24/135 (17.8 %). NF-κB1 genotype and cytomegalovirus infection were significantly associated with risk of aGVHD II-IV (p = 0.022, HR = 3.17, 95 % CI:1.18-8.51 and p = 0.048, HR = 2.56, 95 % CI:1.01-6.52, respectively). In multivariate analysis, NF-κB1homozygous deletion/deletion genotype was the only independent risk factor associated with aGVHD II-IV (p = 0.013, HR = 3.50, 95 % CI:1.30-9.44). No significant association could be observed between miR-146a polymorphism and aGVHD. Combined NF-κB1 and miR146a genotype analysis warrants investigation in a larger cohort. Our preliminary data do not support the association between miR146a and aGVHD, but suggest an association between NF-κB1 and risk of aGVHD that may pave the way for the development of a novel targeted therapy if proved in a larger cohort., Competing Interests: Declaration of Competing Interest No conflict of interest, (Copyright © 2019. Published by Elsevier GmbH.)

Objective: IDH mutations diversely affect the prognosis of cyogenetically normal acute myeloid leukemia (CN-AML) adult patients. The aim of this study is to assess the frequency of IDH mutations and to evaluate its role in AML prognosis., Methods: We have analyzed IDH1 and 2 mutations using High Resolution Melting curve analysis (HRM) in 70 denovo AML patients., Results: The median age of AML patients is 40 years (16-75). Incidence of IDH mutations is 10/70 (14.3%); 2 (2.9%) IDH1 mutant and 8 (11.4%) IDH2 mutant. Median PB blasts of mutant IDH patients was 67.5% (25-96) vs. 44% (0-98) for wild type (p=0.065). Eight/10 (80%) mutant IDH patients had B.M blasts ≥50% vs. 2/10 (20%) <50% (p<0.001) and were classified as intermediate risk cytogenetics (p=0.020) with wild FLT3-ITD (p=0.001). Ten/10 (100%) mutant IDH patients showed wild NPM1 (p=0.049). Median OS of mutant IDH in the intermediate risk cytogenetics was 1.8 years (0.7-3.1) vs. 3.1 years (1.1-5.5) for wild IDH (p=0.05)., Conclusion: IDH mutation is mainly associated with intermediate risk AML and when integrated in this specific subgroup displays a lower survival and can be considered an additional integrated molecular risk marker for AML prognosis., .

The development of hematopoietic stem cell transplantation (HSCT) programs can face significant challenges in most developing countries because such endeavors must compete with other government health care priorities, including the delivery of basic services. While this is may be a limiting factor, these countries should prioritize development of the needed expertise to offer state of the art treatments including transplantation, by providing financial, technological, legal, ethical and other needed support. This would prove beneficial in providing successful programs customized to the needs of their population, and potentially provide long-term cost-savings by circumventing the need for their citizens to seek care abroad. Costs of establishing HSCT program and the costs of the HSCT procedure itself can be substantial barriers in developing countries. Additionally, socioeconomic factors intrinsic to specific countries can influence access to HSCT, patient eligibility for HSCT and timely utilization of HSCT center capabilities. This report describes recommendations from the Worldwide Network for Blood and Marrow Transplantation (WBMT) for establishing HSCT programs with a specific focus on developing countries, and identifies challenges and opportunities for providing this specialized procedure in the resource constrained setting., Competing Interests: Declaration of Competing Interest None of the authors declare any relevant conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: One of the most successful reagents used in the synthesis of the reactive enaminone is DMF-DMA, but it is very expensive with harmful effects on the human health and reacts with special compounds to generate the enaminone such as active methylene centers., Aim: In this article, we synthesized a new ketenaminal by simple method with inexpensive reagents (through desulfurization in diphenylether)., Methods: Thus, a novel reactive ketenaminal (enaminone) was synthesized from the desulfurization of 2-((2-(4-chlorophenyl)-2-oxoethyl)thio)-5,7-bis(4-methoxyphenyl)pyrido[2,3-d]pyrimidin- 4(3H)-one with diphenylether. The starting keteneaminal was coupled with diazotized anilines via the known coupling conditions to give a new series of 2-(4-chlorophenyl)-1-(2-(arylhydrazono)-2- oxoethyl)-5,7-bis(4-methoxy-phenyl)pyrido[2,3-d]pyrimidin-4(1H)-ones., Results: The structures of the new compounds were elucidated based on their IR, 1H-NMR, 13CNMR, and Mass spectra. Moreover, the potency of these compounds as antimicrobial agents has been evaluated. The results showed that some of the products have high activity nearly equal to that of the used standard antibiotic. Additionally, the docking study was done to get the binding mode of the synthesized compounds with the binding site of the DHFR enzyme. The results of molecular docking of the synthesized arylhydrazono compounds are able to fit in DHFR binding site with binding energies ranging from -4.989 to -8.178 Kcal/mol., Conclusion: Our goal was achieved in this context by the synthesis of new ketenaminal from inexpensive reagents, which was utilized in the preparation of bioactive arylhydrazone derivatives., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The present experiment was conducted to evaluate the effect of dietary supplementation with some feed additives (potassium sorbate; Sor, hydrated sodium calcium almuniosilicate; Hsc and L-methionine; L-M) against aflatoxin B1 (AF) toxicity in rabbits. A total of 72 growing rabbits (5-week-old) were distributed into six equal groups (4 replicates with 3 rabbits each). The experimental groups are as follows: control group, AF group (supplemented with AF 0.3 mg/kg diet), AF + Sor group (AF 0.3 mg/kg diet + Sor 2 g/kg diet), AF + Hsc group (AF 0.3 mg/kg diet + Hsc 5 g/kg diet), AF + L-M group (AF 0.3 mg/kg diet + L-M 8 g/kg diet) and AF + Mix group (AF 0.3 mg/kg diet + 2 Sor + 5 Hsc + 8 L-M g/kg diet). Live body weight and weight gain at 13 weeks of age were significantly reduced by AF. Feed intake at 13 weeks of age was decreased in AF, AF + Hsc and AF + Mix compared to the control. AF, AF + Hsc and AF + Mix showed the lowest total antioxidant capacity compared to the control. The highest level of reactive oxygen species and 8-Hydroxy-2-desoxyguanosine was observed in AF group. Using of other supplements with AF increased immunoglobulinM than AF alone. In conclusion, dietary supplementation of Sor, L-M, Hsc or their mixture was effective in reducing the adverse effects of AF on performance, antioxidant and immune status of rabbits with more better improvement obtained by Sor or L-M separately., (© 2019 Blackwell Verlag GmbH.)

The development of hematopoietic stem cell transplantation (HSCT) programs can face significant challenges in most developing countries because such endeavors must compete with other government health care priorities, including the delivery of basic services. Although this is may be a limiting factor, these countries should prioritize development of the needed expertise to offer state-of-the-art treatments, including transplantation, by providing financial, technological, legal, ethical, and other needed support. This would prove beneficial in providing successful programs customized to the needs of their population and potentially provide long-term cost savings by circumventing the need for their citizens to seek care abroad. The costs of establishing an HSCT program and the costs of the HSCT procedure itself can be substantial barriers in developing countries. In addition, socioeconomic factors intrinsic to specific countries can influence access to HSCT, patient eligibility for HSCT, and timely utilization of HSCT center capabilities. This report describes recommendations from the Worldwide Network for Blood and Marrow Transplantation for establishing HSCT programs, with a specific focus on developing countries, and identifies challenges and opportunities for providing this specialized procedure in resource-constrained settings., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

One persistent problem of allogeneic hematopoietic stem cell transplantation (HSCT) is acute graft versus host disease (GVHD). The role of cytokines in the pathogenesis of GVHD has been acknowledged. We aimed, in the current study, to investigate the possibility of prediction of acute GVHD through investigating the pattern of interleukin 12 (IL12) and interferon gamma (IFNγ) production of both patients' origin and donors' origin. A total of 45 patients, receiving allogeneic peripheral blood (PB) stem cells from an identical sibling, were included in the study. Patients' plasma was collected after conditioning, during aplastic phase (representing patients' origin) and after engraftment (representing donors' origin). In addition an aliquot from the graft was used as responders in mixed lymphocyte culture (MLC) for 3 days with patients' mitomycin-treated mononuclear cells as stimulators. Culture supernatant was used for detection of IL12 and IFNγ of donors' origin. Fourteen patients developed acute GVHD. In culture supernatant, IL12 was detectable in 7/14 cases with and in none of 31 cases without acute GVHD (p= <0.001). The corresponding figures for IFNγ were 10/14 and 3/31 with significantly higher IFNγ level in cases with than in cases without acute GVHD (p = 0.001). At engraftment the corresponding figures were 7/14 and 5/31 for IL12 and 11/14 and 7/31 for IFNγ with significantly higher cytokine levels in cases with acute GVHD (p = 0.008 and p = 0.001 respectively). At a cutoff of 0.89 pg/ml, IL12 in culture supernatant may predict acute GVHD with absolute specificity of 100% and a sensitivity of 50%. In conclusion, IL12 and IFNγ of donors' origin not of patients' origin may predict the occurrence of acute GVHD. The MLC model may allow prediction of acute GVHD upfront before conditioning of the patient or mobilization of the donor., (Copyright © 2019. Published by Elsevier GmbH.)

JAK2, CALR, MPL and triple-negative mutational status has a direct impact on symptom severity and disease burden assessed by MPN10 score in myeloproliferative neoplasms (MPNs). Among 93 patients; median MPN10 score was 48 (5-76) in JAK2 mutants versus 25 (4-80) in JAK2 negative (p < .001); 22.5 (4-65) in CALR mutants versus 35 (5-80) in CALR negative (p < .050) and 21 (10-48) in triple negative versus 40 (4-80) in JAK2/CALR/MPL mutants (p < .001). At three years, progression free and overall survival of JAK2-positive versus JAK2-negative patients were 62% versus 100% (p < .001); 85% versus 100% (p = .011) and were 100% versus 78% (p = .067); 100% versus 92% (p = .197) in CALR-positive versus CALR-negative patients and 100% versus 75% (p = .004); 100% versus 90% (p = .015) in triple negative versus mutant patients, respectively. MPN10 score in association with driver gene mutations can be used as a predictor of survival in MPN patients.

Background: Microwave assisted reactions offer a considerable advantages over conventional method reactions because the former results in substantial rate enhancement in a wide range of organic reactions., Objective: we interested herein to prepare new anti-inflammatory and analgesic agents analogues to Indomethacin in short reaction time by using microwaves irradiation., Method: Synthesis of new hydrazonoindolines having thiazole moiety under microwave irradiation were achieved via the reaction of hydrazonoyl chlorides or halogenated active methylene derivatives with thiosemicarbazone derivatives. Also, the utility of the versatile indoline-2,3-dione derivatives in the design of new multifunctional building blocks using condensation with hydrazine derivatives was demonstrated., Results: All products were formed in short reaction time and high yield. The information derived from the spectral data of the formed compounds was confirmed their structures. Also, the analgesic and antiinflammatory activities of the designed derivatives were screened and the results obtained indicated that six derivatives 4g, 9b, 4c, 10b, 4d and 11a revealed the highest anti-inflammatory and analgesic effects., Conclusion: we succeeded in this context to design and synthesis of new anti-inflammatory and analgesic agents analogues to Indomethacin in short reaction time and with high yield., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

The decline of cadmium pollution in fish farms is needed by any adequate method. The present study was designed to explore the effect of dietary cadmium contamination and its amelioration by using dietary clay, probiotic (Bactocell®), vitamin C, and vitamin E supplementation in Nile tilapia fish diet on growth rate, feed efficiency, blood components, and cadmium residues. Fish were separated into 15 groups, each group of fish was stocked into three aquaria and each contains 20 fishes. The fish of the first five groups were fed the basal diet, the second five groups were fed the basal diet contaminated with 25 mg cadmium/kg, and the third five groups were fed the same diet contaminated with 50 mg cadmium/kg. Within each dietary cadmium level, the first group was fed the diet without any supplementation, the second was fed the diet supplemented with natural clay (bentonite) at level 3%, the third group was fed the diet supplemented with 1 g Bactocell®/kg, the fourth group was fed the diet supplemented 50 mg vitamin E/kg, and the fifth group was fed the diet supplemented with 100 mg vitamin C/kg. Live body weight, daily body weight gain, and feed intake of Nile tilapia decreased significantly (P < 0.001) with increasing dietary cadmium level, while feed conversion was impaired. Fish group fed on diets contaminated with 50 mg cadmium/kg recorded the lowest live body weight and weight gain. Serum total protein and albumin concentration significantly (P < 0.001) decreased, while serum creatinine, AST, and ALT significantly (P < 0.001) increased with increasing cadmium level in fish diets. Blood hemoglobin and total erythrocyte (RBCs) significantly (P < 0.001 or 0.05) decreased with cadmium contamination in fish diets, while leukocytes were insignificantly affected. Body cadmium residues increased significantly (P < 0.001) by increasing cadmium level in fish diets. Live body weight, daily body weight gain, and feed intake of Nile tilapia increased significantly (P < 0.001) with feed additive supplementation in diets, also while feed conversion improved. Fish group fed on diets supplemented with probiotic Bactocell® or natural clay recorded higher body weight and gain rate than the other experimental groups. Serum total protein, blood hemoglobin, and total erythrocyte increased, while urea-N, creatinine, ALT, AST, and leukocytes decreased as affected with the feed additive supplementation. Feed additive supplementation in fish diets significantly (P < 0.001) decreased cadmium residues in fish bodies. Irrespective of dietary cadmium level, feed additive supplementation in fish diet improved the growth rate and decreased the concentrations of serum creatinine and ALT. The obtained results indicated that feed additive supplementation could modify the function of the kidney and liver in fish exposed to the cadmium toxicity.

Malignancy is the second most common cause of mortality in the reproductive period and it complicates up to one out of every 1000 pregnancies. When cancer is diagnosed during pregnancy, the management approach must take into consideration both the mother and her fetus. Hematologic cancers diagnosed in pregnancy are not common, resulting in paucity of randomized controlled trials. Diagnosis of such malignancies may be missed or delayed, as their symptoms are similar to those encountered during normal pregnancy. Also, many imaging studies may be hazardous during pregnancy. Management of these malignancies during pregnancy induces many treatment-related risks for mother and baby and should consider patient's preferences for pregnancy continuation. In this article, hematologic malignancies diagnosed in pregnant patients including acute leukemias, chronic myeloid leukemia, lymphomas, multiple myeloma and myeloproliferative neoplasms, will be reviewed, including diagnostic and management strategies and their impact on the pregnant patient and the developing fetus.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) from a geno-identical matched sibling (MSD) is one of the most successful therapies in patients with non-malignant hematological disorders. This study included 273 patients with severe aplastic anemia (SAA), 152 patients with B-Thalassemia major (BTM), 31 patients with Fanconi's anemia (FA), 20 patients with congenital immunodeficiency diseases (ID), and 13 patients with inherited metabolic disorders (IMD) allografted from a MSD. In SAA, the 8-year overall survival (OS) of the whole group patients was 74%. OS was significantly better in patients conditioned with fludarabine and cyclophosphamide (Flu/Cy) than in those who received cyclophosphamide and antithymocyte globulin (Cy/ATG) (p = 0.021). Acute graft-versus-host disease (aGVHD) grade II-IV occurred in 15% while chronic GVHD (cGVHD) occurred in 28%. In BTM, the 12-year disease-free survival (DFS) of the whole group of BTM patients was 72.4%. DFS was 74% for peripheral blood stem cell (PBSC) group compared to 64% in the BM stem cell group. The incidence of graft rejection was significantly lower in patients who received PBSC than in those who received BM (9% vs 25%) (p = 0.036). AGVHD grade II-IV and cGVHD occurred in 15% and 12% of the whole group of BTM patients respectively. In FA, the 5-year OS was 64.5%. Graft rejection occurred in 10% of patients. Grade II-IV aGVHD occurred in 16% while cGVHD occurred in 4%. In ID, the 5-year OS was 62%. Graft rejection occurred in two (10%) patients. Three patients (15%) developed grade II-IV aGVHD, 2 of them progressed to secondary cGVHD. In IMD, OS was 46% at 5 years. Graft rejection occurred in 8% of patients. AGVHD grade II-IV occurred in 15% while cGVHD occurred in 14%. In conclusion, Allo-HSCT provides a higher DFS rate over conventional therapies for patients with non-malignant hematological disorders with prolonged survival.

Unlabelled: Human leukocyte antigen-E (HLA)-E in a non-classical major histocompatibility complex (MHC) class I (Ib) molecule. HLA-E-peptide complex acts as a ligand for natural killer (NK) cells and CD8+ T lymphocytes playing a dual role in natural and acquired immune responses. The difference in expression levels between HLA-E alleles was suggested to have impact on transplantation outcome. The aim of the study is to evaluate the clinical effect of HLA-E alleles on transplantation in a group of Egyptian patients. HLA-E genotyping was analyzed in eighty-eight recipients of stem cell transplantation using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). HLA-E*01:03 allele showed a trend towards lower cumulative incidence of relapse at 2 years compared to homozygous HLA-E*01:01 genotype (8% versus 21.5%, p=0.09, HR: 0.30, 95% CI: 0.91-1.69). HLA-E was the only factor showing near significant association with relapse incidence. HLA-E polymorphism did not affect the cumulative incidence of acute GVHD grades II-IV at 100 days, the 2-year cumulative incidence of extensive chronic GVHD, transplant related mortality (TRM) or overall survival (OS)., Conclusion: the suggested association of HLA-E polymorphism with reduced risk of relapse needs verification in a larger cohort. However, its proposed role in GVL helps better understanding of alloreactivity of T cells and NK cells and their implication in immunotherapy post allogeneic hematopoietic stem cell transplantation., (Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Background: Minimal residual disease (MRD) studies in adult acute lymphoblastic leukemia (ALL) give highly significant prognostic information superior to other standard criteria as age, gender and total leucocytic count (TLC) in distinguishing patients at high and low risk of relapse., Objectives: We aimed to determine the value of MRD monitoring by flowcytometry (FCM) in predicting outcome in adult Precursor ALL patients., Patients and Methods: Bone marrow (BM) samples were analyzed by 4-color FCM collected at diagnosis and after induction therapy (MRD1) to correlate MRD positivity with disease free survival (DFS) and overall survival (OS)., Results: Study included 57 adult ALL patients (44 males and 13 females) with a median age of 22 years (18-49). DFS showed no significant difference with age, gender and initial TLC (p=0.838, 0.888 and 0.743, respectively). Cumulative DFS at 2 years was 34% for B-lineage ALL (n: 35) and 57% for T-lineage ALL (n: 18) (p = 0.057). Cumulative DFS at 2 years was 7% for MRD1 positive (high risk, HR) versus 57% for MRD1 negative patients (Low risk, LR) (p < 0.001). Cumulative DFS at 2 years was 29% for HR patients (n: 26) versus 55% for LR (n: 27) according to GMALL classification (p = 0.064). Cumulative OS did not differ according to age, gender and TLC (p = 0.526, 0.594 and 0.513, respectively). Cumulative OS at 2 years was 36% for B ALL (n: 39) versus 77% for TALL (n: 18) (p = 0.016) and was 49% for Philadelphia chromosome (Ph) negative patients versus 0% for Ph-positive patients (p < 0.001). Regarding MRD1, OS at 2 years was 18% for MRD1 HR (n: 17) versus 65% for MRD1 LR (n: 38) (p < 0.001). OS was 35% for high-risk patients (n: 30) and 62% for low-risk patients (n: 27) classified according to GMALL risk stratification (p = 0.017)., Conclusion: MRD by FCM is a strong independent predictor of outcome in terms of DFS and OS and is a powerful informative parameter in guiding individual treatment in ALL patients., (Copyright © 2013. Production and hosting by Elsevier B.V.)

New series of perimidine derivatives and fused perimidines were derived from the reaction of ketene aminals 1 and 2 with diazotized anilines or hydrazonoyl chlorides. In addition, 8,10-disubstituted-[1,2,4]triazolo[4,3-a]perimidines (20a-m) were prepared through the reaction of perimidine-2-thione (15) with hydrazonoyl chlorides. The structures of the newly synthesized compounds were established on the basis of spectral data and elemental analyses. Some products were investigated for their antitumor activities against the human breast cancer cell line MCF-7 and the liver carcinoma cell line HEPG-2, and the results of some derivatives showed promising activity., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Wilms' tumor (WT1) gene overexpression has been reported in the majority of acute myeloid leukemia (AML) patients at diagnosis and has been evaluated as prognostic and minimal residual disease (MRD) marker., Patients and Methods: WT1 overexpression was evaluated in 68 adult AML patients at diagnosis and at the end of induction using quantitative real-time polymerase chain reaction (PCR)., Results: No significant associations were encountered between WT1 overexpression at diagnosis and other prognostic factors. Complete remission (CR) was achieved in 74% of the patients with WT1 overexpression compared to 80% of patients with normal levels (P = 0.5). No significant associations were encountered between WT1 overexpression at diagnosis and disease-free survival (DFS) or overall survival (OS) (P = 0.6 and 0.3, respectively). At the end of induction, the median duration of DFS in patients achieving ≥ 2 log reduction was not reached compared to only 5 months (range: 2.1-7.9 months) in those attaining <2 log reduction (P = 0.2). The median duration of OS in patients achieving ≥ 2 log reduction was 13 months (range: 0-33.3 months) compared to 7.5 months (5.4-9.6 months) in those attaining <2 log reduction (P = 0.2). The survival at 1 year in patients achieving ≥ 2 log was double the group with <2 log reduction (67% compared to 33%)., Conclusion: Our results, although not reaching the level of significance, probably due to the small sample size, still suggest that the early assessment of WT1 transcript level at the end of induction in patients in CR may have a prognostic significance on clinical outcome and may thus be a useful marker for risk stratification especially in patients lacking disease-specific marker.

Hematopoietic stem cell transplantation (HSCT) activity was surveyed in the 9 countries in the World Health Organization Eastern Mediterranean region that reported transplantation activity. Between the years of 1984 and 2007, 7933 transplantations were performed. The number of HSCTs per year has continued to increase, with a plateau in allogeneic HSCT (allo-HSCT) between 2005 and 2007. Overall, a greater proportion of transplantations were allo-HSCT (n = 5761, 77%) compared with autologous HSCT (ASCT) (n = 2172, 23%). Of 5761 allo-HSCT, acute leukemia constituted the main indication (n = 2124, 37%). There was a significant proportion of allo-HSCT for bone marrow failures (n = 1001, 17%) and hemoglobinopathies (n = 885, 15%). The rate of unrelated donor transplantations remained low, with only 2 matched unrelated donor allo-HSCTs reported. One hundred umbilical cord blood transplantations were reported (0.017% of allo-HSCT). Peripheral blood stem cells were the main source of graft in allo-HSCT, and peripheral blood stem cells increasingly constitute the main source of hematopoietic stem cells overall. Reduced-intensity conditioning was utilized in 5.7% of allografts over the surveyed period. ASCT numbers continue to increase. There has been a shift in the indication for ASCT from acute leukemia to lymphoproliferative disorders (45%), followed by myeloma (26%). The survey reflects transplantation activity according to the unique health settings of this region. Notable differences in transplantation practices as reported to the European Group for Blood and Marrow Transplantation over recent years are highlighted., (Copyright © 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Several centers are now performing allogeneic hematopoietic stem cell transplantation (HSCT) in the World Health Organization Eastern Mediterranean Region (EMRO) but the availability is still limited due to high cost and the need for multi-disciplinary team and an advanced laboratory support. Special issues including compatible donor availability, potential for alternate donor programs, differences in pattern of disease, pre-HSCT general status particularly for patients with BM failure, high sero-positivity for CMV, Hepatitis B and C infection and specific observations about GVHD with its relation to genetically homogeneous community are discussed. A total of 17 HSCT programs (performing five or more HSCTs annually) exist in nine countries of the EM region. Only six programs are currently reporting to EBMT or IBMTR. A total of 7617 HSCTs including 5701 allogeneic HSCTs have been performed. Due to low HSCT team density (1.5583 teams/10 million inhabitants versus 14.4333 in Europe) and very low HSCT team distribution (0.2729 teams/10,000 sq km area versus <1 to 6 teams in Europe) only 70.8% of total population has access to such a program in EM region. GNI/capita had no clear association with low HSCT activity; however improvement in infrastructure and establishment of EM regional HSCT registry need prioritization., ((c) 2010 Elsevier Ltd. All rights reserved.)

Purpose: To assess the kinetics of molecular response to Imatinib Mesylate (IM) therapy in predicting progression free survival (PFS), sustained hematological, and cytogenetic responses in CPCML., Methods: Ninety five newly diagnosed CPCML Egyptian patients were treated with IM 400 mg daily dose. Cytogenetic analysis was performed at diagnosis and every 6 months. Molecular monitoring by RT-QPCR was performed at diagnosis and every 3 months during a median follow-up period (FUp) of 26 months. Mutation detection of ABL domain was performed by ASO-PCR., Results: Hematological response was 98% after three months of IM therapy. Out of 95 patients 59 showed 2 log reduction of BCR-ABL/ABL ratio after 6 months of whom 49 (83%) had complete cytogenetic response (CCyR) and 42 (71%) had major molecular response (MMR) at 12 months. BCR-ABL transcripts remained undetectable in 22 patients (39%) at 26 months. Among the remaining 34 patients not achieving 2 log reduction at 6 months only 5 (15%) had CCyR and MMR by 12 months. ABL domain mutations were detected in 11/15 (73%) resistant and suboptimal responding patients. Achieving 2 log reduction after 6 months of IM therapy significantly correlated with sustained cytogenetic and molecular responses (p<0.0001), with PFS at 2 years (p<0.03) and inversely with ABL gene mutations (p<0.001)., Discussion: These data demonstrated the predictive value of early molecular response to IM in CPCML regarding disease course and PFS. A 2 log reduction at 6 months of IM treatment could be a cut off level predicting resistance, CCyR, or suggesting IM dose modification.

Although several centers are now performing allogeneic hematopoietic SCT (HSCT) in the Eastern Mediterranean (EM) region, the availability is still limited. Special issues including compatible donor availability and potential for alternative donor programs are discussed. In comparison to Europe and North America, differences in patterns of diseases and pre-HSCT general status, particularly for patients with BM failure, are described. Other differences including high sero-positivity for CMV, hepatitis B and C infection, and specific observations about GVHD and its relation to genetically homogeneous communities are also discussed. We report that a total of 17 HSCT programs (performing five or more HSCTs annually) exist in 9 countries of the EM region. Only six programs are currently reporting to European Group for Blood and Marrow Transplantation or Center for International Blood and Marrow Transplantation Research. A total of 7617 HSCTs have been performed by these programs including 5701 allogeneic HSCTs. The area has low-HSCT team density (1.56 teams per 10 million inhabitants vs 14.43 in Europe) and very low-HSCT team distribution (0.27 teams per 10 000 sq km area vs <1-6 teams in Europe). Gross national income per capita had no clear association with low-HSCT activity. Much improvement in infrastructure and formation of an EM regional HSCT registry are needed.

Hematopoietic SCT is now an established treatment modality with definitive indications for many hematological disorders. However, this line of treatment requires tremendous resources, and it becomes increasingly difficult for transplanters practicing in the developing world to reconcile the difference between what is possible and what is available. On the basis of 18 years of experience and more than 1300 transplants, this article will focus on special issues, which we think are important for hematopoietic SCT practices in developing countries, taking the program in Egypt as an example that may be applicable to other countries in the developing world. The SCT program in Egypt started in 1989 on a narrow scale. In 1997, the transplant rate increased dramatically with the opening of the SCT unit at the Nasser Institute. Our team is registered in the Center for International Blood and Marrow Transplant Research. The total number of transplants performed till June 2007 is 1362; 80% of the cases are allogeneic and 20% autologous. There are seven other centers in Egypt performing mainly autologous transplants.

Our objective was to evaluate, probably for the first time, the impact of CD34 subsets on engraftment kinetics in allogeneic PBSC transplantation (PBSCT). PBSC graft components were analyzed in 62 cases for the absolute count/kg of total CD34+ and the following subsets: DR- and +, CD71+/-, CD38+/-, CD33+/- and CD61+/-. Time to ANC >0.5 and >1 x 10(9)/l and platelets >20 and >50 x 10(9)/l was reported. The median value for each parameter was used to discriminate rapid from slow engraftment. Four parameters showed significant predictive power of early neutrophil engraftment, namely CD34+ /DR- (P = 0.002), CD34+/38- (P = 0.02), CD34+/CD61- (P = 0.04) and total CD34+ cell dose (P = 0.04). Four parameters showed significant predictive power of early platelet engraftment, namely CD34+/CD61+ (P = 0.02), CD34+ /CD38- and total CD34+ cell dose (P = 0.04) and CD34+ /CD71- (P = 0.05). Comparing patients who received > to those who received < the threshold dose(s), only CD34+ /CD38- lost its significance for neutrophil engraftment; and only CD34+ /CD61+ retained its significance for platelet engraftment (P = 0.03); furthermore, the former group required significantly fewer platelet transfusions (P = 0.018). We concluded that in allogeneic PBSCT, the best predictor of early neutrophil engraftment is the absolute CD34+ /DR- and for early platelet engraftment is the absolute CD34+ /CD61+ cell dose.