Design and synthesis of new quinazolinone derivatives: investigation of antimicrobial and biofilm inhibition effects.

New quinazolin-4-ones 9-32 were synthesized in an attempt to overcome the life-threatening antibiotic resistance phenomenon. The antimicrobial screening revealed that compounds 9, 15, 16, 18, 19, 20 and 29 are the most broad spectrum antimicrobial agents in this study with safe profile on human cell lines. Additionally, compounds 19 and 20 inhibited biofilm formation in Pseudomonas aeruginosa, which is regulated by quorum sensing system, at sub-minimum inhibitory concentrations (sub-MICs) with IC50 values 3.55 and 6.86 µM, respectively. By assessing other pseudomonal virulence factors suppression, it was found that compound 20 decreased cell surface hydrophobicity compromising bacterial cells adhesion, while both compounds 19 and 20 curtailed the exopolysaccharide production which constitutes the major component of the matrix binding biofilm components together. Also, at sub-MICs Pseudomonas cells twitching motility was impeded by compounds 19 and 20, a trait which augments the cells pathogenicity and invasion potential. Molecular docking study was performed to further evaluate the binding mode of candidates 19 and 20 as inhibitors of P. aeruginosa quorum sensing transcriptional regulator PqsR. The achieved results demonstrate that both compounds bear promising potential for discovering new anti-biofilm and quorum quenching agents against Pseudomonas aeruginosa without triggering resistance mechanisms as the normal bacterial life cycle is not disturbed.

Aloe vera gel relieves cadmium triggered hepatic injury via antioxidative, anti-inflammatory, and anti-apoptotic routes.

Aloe vera (AV) gel extracted from fresh AV leaves was chosen in this study to evaluate its antioxidant, anti-inflammatory, and antiapoptotic activities against cadmium (Cd) -induced liver injury. Forty Wistar male adult rats were equally divided into four groups. Group I (standard control) ingested with 2.5 ml/kg b.w. of physiological saline. Group II (Cd-intoxicated) received 3 mg/kg b.w./day of CdCl2 dissolved in saline. Group III (AV) received 200 mg/kg b.w./day of AV gel dissolved in saline. Group IV (Cd+AV) ingested with 200 mg/kg b.w./day of AV gel solution along with 3 mg/kg b.w. CdCl2. All groups were ingested orally by gavage for 3 consecutive weeks. Paraoxonase-1 (PON-1) and HSP70 were measured in serum. The deposited Cd level, nitric oxide content, lipid peroxidation, collagen-1 (COL-1), and metalloproteinase-9 (MMP-9) levels were all determined in liver tissue homogenates. Gene expression of NF-κB and IL-6, Bax, and Bcl2, as well as immunohistochemistry analysis of activated caspase-3, was performed. Results showed that ingestion of AV gel greatly relieved all oxidative stress due to Cd exposure, modulated the NF-κB, IL-6, Bax, and Bcl2 expression levels, and improved the apoptotic state. In conclusion, AV gel confirmed its potential ameliorating effect against liver injury induced due to Cd exposure.

Novel thiazolidin-4-one benzenesulfonamide hybrids as PPARγ agonists: Design, synthesis and in vivo anti-diabetic evaluation.

In the current study, two series of novel thiazolidin-4-one benzenesulfonamide arylidene hybrids 9a-l and 10a-f were designed, synthesized and tested in vitro for their PPARÉ£ agonistic activity. The phenethyl thiazolidin-4-one sulphonamide 9l showed the highest PPARÉ£ activation % by 41.7%. Whereas, the 3-methoxy- and 4-methyl-4-benzyloxy thiazolidin-4-one sulphonamides 9i, and 9k revealed moderate PPARÉ£ activation % of 31.7, and 32.8%, respectively, in addition, the 3-methoxy-3-benzyloxy thiazolidin-4-one sulphonamide 10d showed PPARÉ£ activation % of 33.7% compared to pioglitazone. Compounds 9b, 9i, 9k, 9l, and 10d revealed higher selectivity to PPARÉ£ over the PPARδ, and PPARα isoforms. An immunohistochemical study was performed in HepG-2 cells to confirm the PPARÉ£ protein expression for the most active compounds. Compounds 9i, 9k, and 10d showed higher PPARÉ£ expression than that of pioglitazone. Pharmacological studies were also performed to determine the anti-diabetic activity in rats at a dose of 36 mg/kg, and it was revealed that compounds 9i and 10d improved insulin secretion as well as anti-diabetic effects. The 3-methoxy-4-benzyloxy thiazolidin-4-one sulphonamide 9i showed a better anti-diabetic activity than pioglitazone. Moreover, it showed a rise in blood insulin by 4-folds and C-peptide levels by 48.8%, as well as improved insulin sensitivity. Moreover, compound 9i improved diabetic complications as evidenced by decreasing liver serum enzymes, restoration of total protein and kidney functions. Besides, it combated oxidative stress status and exerted anti-hyperlipidemic effect. Compound 9i showed a superior activity by normalizing some parameters and amelioration of pancreatic, hepatic, and renal histopathological alterations caused by STZ-induction of diabetes. Molecular docking studies, molecular dynamic simulations, and protein ligand interaction analysis were also performed for the newly synthesized compounds to investigate their predicted binding pattern and energies in PPARÉ£ binding site.

Design, Synthesis, and Molecular Docking of Novel Miscellaneous Chalcones as p38α Mitogen-Activated Protein Kinase Inhibitors.

New chalcones were synthesized and evaluated to serve as p38-α type of mitogen-activated protein kinase (MAPK) inhibitors. According to the National Cancer Institute, the findings indicated that at a 10 µM dosage, compounds 3a and 6 were the most active among all the compounds examined, with mean growth inhibition% of 94.83 and 58.49, respectively. In 5-dose testing, they showed anticancer activity in the micro-molar range with GI50 in the range of 1.41-46.1 and 2.07-31.3 µM, respectively. Besides, powerful activity, especially against the leukaemia cell lines and good selectivity to cancer cells compared to normal PCS-800-017 with a selectivity index=12.41 and 23.77, respectively. Compounds 3a and 6 inhibited p38α MAPK with IC50 values of 0.1462±0.0063 and 0.4356±0.0189 µM, correspondingly. 3a showed good inhibition for HL-60(TB) cells and induced cell cycle arrest in HL-60(TB) cells at the G2/M phase. Besides, it elevated the total apoptosis by 14.68-fold and increased the caspase-3 level by 3.52-fold compared with doxorubicin, which raised it by 4.30-fold, inducing apoptosis by acting as caspase-dependent inducers. These results suggest that 3a is a promising antiproliferative and p38α MAPK inhibitor, confirmed by molecular docking with high compatibility 3a with the p38α MAPK binding site.

Growth performance, nutrient digestion, rumen fermentation and blood biochemistry in response to partially replacing cottonseed cake with sesame meal in a lamb feedlot diet.

Recently, it is necessary to formulate high-quality, balanced and low-cost rations for ruminants from nontraditional sources. The present study conducted to investigate the impact of partially replacing corticated cottonseed (CS) cake with sesame meal (SM) in a lamb feedlot diet on growth performance, nutrient digestion, rumen fermentation and blood biochemistry. Fifteen growing lambs with an initial body weight of 27.4 ± 1.2 kg (6-7 months old) were randomly assigned into three equal groups (n = 5). Lambs in control group (CS) fed a basal diet, while 8% and 16% SM were used to replace an equal portion of corticated CS cake in the second (8SM) and third (16SM) groups respectively. Results showed that most parameters of growth performance and nutrient digestibility were significantly improved (p < 0.05) with the partial replacement of SM (8SM and/or 16SM). Regarding ruminal parameters, ruminal pH and total volatile fatty acids concentration increased (p < 0.05), while ammonia level and total protozoa count decreased with the partial replacement of SM. Moreover, blood parameters showed variant responses to SM partial replacement. Total protein increased, and glucose decreased significantly with 16SM, while cholesterol showed a significant decreasing with both SM replacement levels. SM may substitute CS cake in lamb diet without detrimental effects on performance, digestibility and ruminal fermentation.

Novel pyrazolo[3,4-d]pyrimidine derivatives: design, synthesis, anticancer evaluation, VEGFR-2 inhibition, and antiangiogenic activity.

A novel series of 12 pyrazolo[3,4-d]pyrimidine derivatives were created and evaluated in vitro for their antiproliferative activity against the NCI 60 human tumor cell line panel. Compounds 12a-d displayed significant antitumor activity against MDA-MB-468 and T-47D (breast cancer cell lines), especially compound 12b, which exhibited the highest anticancer activity against MDA-MB-468 and T-47D cell lines with IC50 values of 3.343 ± 0.13 and 4.792 ± 0.21 µM, respectively compared to staurosporine with IC50 values of 6.358 ± 0.24 and 4.849 ± 0.22 µM. The most potent cytotoxic derivatives 12a-d were studied for their VEGFR-2 inhibitory activity to explore the mechanism of action of these substances. Compound 12b had potent activity against VEGFR-2 with an IC50 value of 0.063 ± 0.003 µM, compared to sunitinib with IC50 = 0.035 ± 0.012 µM. Moreover, there was an excellent reduction in HUVEC migratory potential that resulted in a significant disruption of wound healing patterns by 23% after 72 h of treatment with compound 12b. Cell cycle and apoptosis investigations showed that compound 12b could stop the cell cycle at the S phase and significantly increase total apoptosis in the MDA-MB-468 cell line by 18.98-fold compared to the control. Moreover, compound 12b increased the caspase-3 level in the MDA-MB-468 cell line by 7.32-fold as compared to the control.

Synthetic non-toxic anti-biofilm agents as a strategy in combating bacterial resistance.

The tremendous increase in the bacterial resistance to the available antibiotics is a serious problem for the treatment of various infections. Biofilm formation in bacteria significantly contributes to the bacterial survival in host cells, and is considered as an crucial factor, responsible for bacterial resistance. The response of the bacterial cells in the biofilm to antibiotics is completely different from that of the free floating planktonic cells of the same strain. The anti-biofilm agents that could inhibit the biofilm production without affecting the bacterial growth, apply less selective pressure over the bacterial strains than the traditional antibiotics; thus the development of bacterial resistance would be of low incidence. Many attempts have been performed to discover novel agents capable of interfering with the bacterial biofilm life cycle, and several compounds have shown promising activities in suppressing the biofilm production or in dispersing mature existing biofilms. This review describes the different chemical classes that have anti-biofilm effects against different Gram-positive and Gram-negative bacteria without affecting the bacterial growth.

Quercetin and L-Arginine Ameliorated the Deleterious Effects of Copper Oxide Nanoparticles on the Liver of Mice Through Anti-inflammatory and Anti-apoptotic Pathways.

The widespread use and applications of copper oxide nanoparticles (CuO NPs) in daily life make human exposure to these particles inevitable. This study was carried out to investigate the deteriorations in hepatic and serum biochemical parameters induced by CuO NPs in adult male mice and the potential ameliorative effect of L-arginine and quercetin, either alone or in combination. Seventy adult male mice were equally allocated into seven groups: untreated group, L-arginine, quercetin, CuO NPs, arginine + CuO NPs, quercetin + CuO NPs, and quercetin + arginine + CuO NPs. Treating mice with CuO NPs resulted in bioaccumulation of copper in the liver and consequent liver injury as typified by elevation of serum ALT activity, reduction in the synthetic ability of the liver indicated by a decrease in the hepatic arginase activity, and serum total protein content. This copper accumulation increased oxidative stress, lipid peroxidation, inflammation, and apoptosis as manifested by elevation in malondialdehyde, nitric oxide, tumor necrosis factor-α, the expression level of caspase-3 and bax quantified by qPCR, and the activity of caspase-3, in addition to the reduction of superoxide dismutase activity. It also resulted in severe DNA fragmentation as assessed by Comet assay and significant pathological changes in the liver architecture. The study proved the efficiency of quercetin and L-arginine in mitigating CuO NPs-induced sub-chronic liver toxicity due to their antioxidant, anti-inflammatory, and anti-apoptotic properties; ability to inhibit DNA damage; and the potential as good metal chelators. The results of histopathological analysis confirmed the biochemical and molecular studies.

Pyridazine derivatives as selective COX-2 inhibitors: A review on recent updates.

Selective cyclooxygenase (COX)-2 inhibitors have several advantages over nonselective COX inhibitors (nonsteroidal anti-inflammatory drugs [NSAIDs]), including the absence of adverse effects (renal and hepatic disorders) associated with the long-term use of standard NSAIDs, as well as an improved gastrointestinal profile. The pyridazine nucleus is regarded as a promising scaffold for the development of powerful COX-2 inhibitors, particularly when selectively functionalized. This article summarizes some methods for the synthesis of pyridazine derivatives. Furthermore, it covers all of the pyridazine derivatives that have appeared as selective COX-2 inhibitors, making it useful as a reference for the rational design of novel selective COX-2 inhibitors.

Design, synthesis, anticancer evaluation, and in silico studies of some thieno[2,3-d]pyrimidine derivatives as EGFR inhibitors.

New series of 20 thieno[2,3-d]pyrimidine derivatives have been synthesized. The National Cancer Institute evaluated all the newly synthesized compounds for their antiproliferative activity against a panel of 60 cancer cell lines. Compound 7b exhibited a remarkable antineoplastic activity at 10 µM dose and was therefore tested at five dose concentrations. The significant and broad-spectrum antineoplastic action of compound 7b was observed against 37 of the tested cancer cell lines with a dose that inhibits 50% of the growth compared to control values in the micromolar range of 1.95-9.6 µM. The dose which inhibits the growth completely in the cytostatic range of 3.99-100 µM was also observed. Compound 7b effectively inhibited epidermal growth factor receptor (EGFR) with 50% inhibition concentration value (IC50 ) = 0.096 ± 0.004 compared to erlotinib with IC50 = 0.037 ± 0.002. Moreover, compound 7b revealed a powerful downregulation effect on total EGFR concentration and its phosphorylation. In addition, compound 7b inhibited phosphatidylinositol 3-kinase, protein kinase B, and the mammalian target of rapamycin pathway phosphorylation. Furthermore, compound 7b raised total apoptosis by 21.93-fold in the ovarian cancer cell line (OVCAR-4) and caused an arrest in the cell cycle in the G1/S phase. It also raised the level of caspase-3 by 4.72-fold. Furthermore, to determine the binding manner of the most effective derivatives and validate their capacity to comply with the pharmacophoric properties necessary for EGFR inhibition, they were docked into the active site of the EGFR.

Design, synthesis, anticancer, and antibacterial evaluation of some quinazolinone-based derivatives as DHFR inhibitors.

Two series of quinazolinone derivatives were designed and synthesized as dihydrofolate reductase (DHFR) inhibitors. All compounds were evaluated for their antibacterial and antitumor activities. Antibacterial activity was evaluated against three strains of Gram-positive and Gram-negative bacteria. Compound 3d exhibited the highest inhibitory activity against Staphylococcus aureus DHFR (SaDHFR) with IC50 of 0.769 ± 0.04 µM compared to 0.255 ± 0.014 µM for trimethoprim. Compound 3e was also more potent than trimethoprim against Escherichia coli DHFR (EcDHFR) with IC50 of 0.158 ± 0.01 µM and 0.226 ± 0.014 µM, respectively. Compound 3e exhibited a promising antiproliferative effect against most of the tested cancer cells. It also showed potent activity against leukemia (CCRF-CEM, and RPMI-8226); lung NCI-H522, and CNS U251 with GI% of 65.2, 63.22, 73.28, and 97.22, respectively. The cytotoxic activity of compound 3e was almost half the activity of doxorubicin against CCRF-CEM cell line with IC50 of 1.569 ± 0.06 µM and 0.822 ± 0.03 µM, respectively. In addition, compound 3e inhibited human DHFR with IC50 value of 0.527 ± 0.028 µM in comparison to methotrexate (IC50 = 0.118 ± 0.006 µM). Compound 3e caused an arrest of the cell cycle mainly at the S phase and caused a rise in the overall apoptotic percentage from 2.03% to 48.51%. (23.89-fold). Treatment of CCRF-CEM cells with compound 3e produced a significant increase in the active caspase-3 level by 6.25-fold compared to untreated cells. Molecular modeling studies were performed to evaluate the binding pattern of the most active compounds in the bacterial and human DHFR.

Design and synthesis of novel hexahydrobenzo[4,5]thieno[2,3-d]pyrimidine derivatives as potential anticancer agents with antiangiogenic activity via VEGFR-2 inhibition, and down-regulation of PI3K/AKT/mTOR signaling pathway.

New thieno[2,3-d]pyrimidine derivatives were designed and synthesized. The National Cancer Institute (NCI) evaluated the synthesized novel compounds against a panel of 60 tumor cell lines for their antiproliferative activity. Compounds 6b, 6f, and 6g showed potent anticancer activity at 10 µM dose, with mean GI of 20.86%, 76.41%, and 31.49%, respectively. Compound 6f was selected for five-dose concentrations evaluation. Compound 6f scored a submicromolar range of GI50 values against 10 cancer cell lines, indicating broad-spectrum and potent antiproliferative activity. Compound 6f TGI values were recorded in the cytostatic range of 4.02-95.1 µM. In comparison to sorafenib, the tested compounds 6b, 6f, and 6g inhibited VEGFR-2 with IC50 values of 0.290 ± 0.032, 0.066 ± 0.004, and 0.16 ± 0.006 µM, correspondingly. Compound 6f significantly reduced the total VEGFR-2 expression and its phosphorylation. Additionally, 6f reduced the phosphorylation of PI3K, Akt, and mTOR pathway proteins. Moreover, the migratory potential of HUVECs was significantly reduced, after 72 h of treatment with compound 6f, resulting in disrupted wound healing patterns which verified the angiogenesis suppression properties of compound 6f. Compound 6f increased the total apoptosis percentage by 21.27-fold compared to sorafenib, which caused a 24.11-fold increase in the total apoptosis percentage. This apoptotic activity was accompanied by a 7.81-fold increase in the level of apoptotic caspase-3. Furthermore, the cell cycle analysis revealed that the target derivative 6f reduced cellular proliferation and induced an arrest in HCT-15 colon cancer cell cycle at the S phase. Molecular modeling was used to determine the binding profile and affinity of derivative 6f toward the VEGFR-2 active site.

Modulation of Immunity, Antioxidant Status, Performance, Blood Hematology, and Intestinal Histomorphometry in Response to Dietary Inclusion of Origanum majorana in Domestic Pigeons' Diet.

This experiment was conducted to evaluate the effect of adding Origanum majorana (OM) powder to domestic pigeon diets on growth performance, feeding and drinking behaviour, blood hematology, blood biochemical parameters, blood inflammatory and oxidative markers, carcass characteristics, the weights of lymphoid organs, and and intestinal cecal, and bursa of Fabricius histology. A random distribution of fifty-four unsexed pigeon squabs (30 days old, average body weight; 321 g ± 7.5) into three groups was done. The first group was fed the grower basal diet without adding OM powder, while OM powder was added at levels of 0.5 and 1% to the basal diets of the second and third groups, respectively. The changes in growth performance parameters and feeding and drinking behavior under OM powder's effect were insignificant. However, the lymphoid organs (spleen and thymus) significantly increased in weight (p < 0.05) in the OM-fed groups. Moreover, blood examination showed positive responses to OM powder in terms of blood cell counts (RBCs andWBCs), and the values of hemoglobin, hematocrit, mean corpuscular volume, lymphocyte numbers, levels of globulin, and glutathione peroxidase enzyme were significantly increased. The numbers of heterophils, the ratio of heterophil to lymphocyte, malondialdehyde levels were reduced (p < 0.05). Histomorphometry examination revealed increases in intestinal villi height, cecal thickness, and bursal follicle area and number. These results indicated that adding OM powder to the pigeon diet may improve their immunity, increase their antioxidant status, and correct some hematological disorders.

Coumarin derivatives with potential anticancer and antibacterial activity: Design, synthesis, VEGFR-2 and DNA gyrase inhibition, and in silico studies.

A series of coumarin derivatives were designed, synthesized, and evaluated for their antiproliferative activity. Compound 3e exhibited significant antiproliferative activity and was further evaluated at five doses at the National Cancer Institute. It effectively inhibited vascular endothelial growth factor receptor-2 (VEGFR-2) with an IC50 value of 0.082 ± 0.004 µM compared with sorafenib. While compound 3e significantly downregulated total VEGFR-2 and its phosphorylation, it markedly reduced the HUVEC's migratory potential, resulting in a significant disruption in wound healing. Furthermore, compound 3e caused a 22.51-fold increment in total apoptotic level in leukemia cell line HL-60(TB) and a 6.91-fold increase in the caspase-3 level. Compound 3e also caused cell cycle arrest, mostly at the G1/S phase. Antibacterial activity was evaluated against Gram-positive and Gram-negative bacterial strains. Compound 3b was the most active derivative, with the same minimum inhibitory concentration and minimum bactericidal concentration value of 128 µg/mL against K. pneumonia and high stability in mammalian plasma. Moreover, compounds 3b and 3f inhibited Gram-negative DNA gyrase with IC50 = 0.73 ± 0.05 and 1.13 ± 0.07 µM, respectively, compared to novobiocin with an IC50 value of 0.17 ± 0.02 µM. The binding affinity and pattern of derivative 3e toward the VEGFR-2 active site and compounds 3a-c and 3f in the DNA gyrase active site were evaluated using molecular modeling. Overall, ADME studies of the synthesized coumarin derivatives displayed promising pharmacokinetic properties.

Safety and reported adverse effects of coronavirus disease-2019 (COVID-19) vaccines in patients with rheumatic diseases.

Background: Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Symptoms and severity of COVID19 are variable. Aim of the work: To evaluate the effectiveness and to identify side effects of the COVID-19 vaccines among Egyptian patients with autoimmune rheumatic diseases (RDs). Patients and methods: The study included 126 patients with various RDs and 200 control. Detailed medical history was recorded with special concern regarding COVID-19 vaccination, types, doses, side effects, post-vaccination infection and treatment. Results: In patients, BBIBP-CorV (Sinopharm) was the most frequent vaccine 42.3 % (n = 52); CoronaVac (Sinovac) 22 % (n = 27); ChAdOx1 (AstraZeneca) 17.9 % (n = 22); BNT162 (Pfizer BioNTech) 14.6 % (n = 18); Sputnik V 1.6 % (n = 2) and Ad26.COV2-S (Johnson & Johnson) 1.6 % (n = 2). Regarding the control, 34.4 % (n = 62) received AstraZeneca; 26.1 % (n = 47) Sinopharm; 16.7 % (n = 30) Pfizer; 11.7 % (n = 21) Sinovac; 6.7 % (n = 12) Sputnik; 3.3 % (n = 6) Johnson & Johnson and 1.2 % (n = 2) mRNA1273 (Moderna). COVID-19 infection decreased after vaccination from 32 (25.4 %) to 7 (5.6 %), and from 162 (81.0 %) to 85 (42.7 %) in RD patients and the control respectively. ICU admission decreased from (6.3 %) among RD patients and from (1.3 %) in control to 0 % after vaccination in both groups. In RD patients, body ache was the commonest reported vaccine adverse effect (44.4 %). Pain at the injection site was the commonest among control (77 %). ChAdOx1 (AstraZeneca) had the highest incidence of side effects, mRNA1273 (Moderna) showed the lowest. Conclusion: COVID-19 vaccine was effective in decreasing infection and disease severity in RDs patients and control, with similar, mild adverse effects.

An application of the ecological model to sexual harassment in informal areas of Cairo, Egypt.

Street-based sexual harassment is a prevalent but understudied form of gender-based violence that restricts women's access to public spaces. Drawing on adaptations of the ecological model that identify the root causes of gender-based violence in patriarchy, in this study, we explore the causes of street harassment in informal areas of Greater Cairo. Our analysis is based on qualitative interviews and focus groups with male and female youth aged 13-29 years, parents of youth and community leaders in two informal areas. We supplement the qualitative data with descriptive analysis of a representative, 2016 survey of youth in informal areas of Cairo that measured experiences with and attitudes toward harassment. Harassment was prevalent in the study areas, and respondents tended to place the blame for harassment at the individual level of the ecological model, particularly women's behavior. However, there were also community- and societal-level factors that contributed to the prevalence of harassment. Patriarchal norms and stigmatization of women who are harassed reinforced victim-blaming, such that most young women were afraid to report experiences of harassment due to social censure. In this context, educational or awareness raising interventions are unlikely to be effective in combating harassment, which is widely acknowledged to be a problem. Rather, interventions are needed along the different levels of the ecological model to target peer group and community norms that encourage harassment, address harassment in schools and strengthen reporting mechanisms.

Effect of Dietary Microalgae (Spirulina platensis) on Growth Performance, Ingestive Behavior, Hemato-Biochemical Parameters, and Economic Efficiency of Fayoumi Broilers.

This study was conducted to evaluate the effect of dietary supplementation with Spirulina platensis (SP) on the productive performance, carcass characteristics, behavior, blood serum metabolites, hematological indices, and economic efficiency of Fayoumi broiler chickens for a 56-day. In total, 120 one-day-old broiler chicks were randomly distributed among four dietary treatments with three replicates (n = 10/group) for 8 weeks. The dietary treatments were a control basal diet without SP and the same basal diets supplemented with 0.25, 0.5, or 1.0% SP. Birds fed 1% Spirulina-supplemented diets recorded significantly (p < 0.05) higher body weight, weight gain, and feed conversion ratio and less overall feed intake and feeding behavior than those in the control group. No significant changes (p > 0.05) were recorded in the dressing percentage or the relative weights of internal organs among the different experimental groups, except for the thymus. Diets containing 0.5 or 1.0% SP saw an increase (p < 0.05) in serum total protein and globulin and a reduction (p < 0.05) in serum cholesterol concentration. The lymphocyte percentage in birds fed SP diets was significantly (p < 0.05) higher than in birds fed the control diet. These results suggest that adding SP up to 1% to the broiler diets could positively affect some important blood biochemical parameters, enhance their immunity response, and improve their growth performance. However, from an economic point of view, supplementation with 0.25% of SP is recommended for Fayoumi broiler chickens.

Hepatoprotective effect of ferulic acid and/or low doses of γ-irradiation against cisplatin-induced liver injury in rats.

The therapeutic efficacy of cisplatin (CIS) is limited owing to its hepatotoxic side effects. The current study aimed to investigate the protective impact of ferulic acid (FA) and low-doses of γ-irradiation (LDR) against CIS-prompted hepatotoxicity in rats. Adult male Swiss albino rats were divided into eight groups: untreated group; FA, LDR, and CIS treated groups; and combinations of one or more of the above treatments. Post-treatment analyses included measuring redox markers like SOD and CAT activity, NO free radical content, and lipid peroxidation in liver tissue. Serum aminotransferase activities were also determined. Additionally, gene transcript levels of liver NF-Ò¡B-P65, caspase-1, COX-2, and IL-1ß were quantified. Moreover, immunohistochemistry for caspase-3 and histopathological examinations were estimated in liver tissue. Our findings revealed increased levels of oxidative stress along with a significant reduction in anti-oxidative responses and a significant increase in serum aminotransferase activities in the CIS-intoxicated group. A similar increase was also observed in COX-2 and IL-1ß transcript levels and caspase-3 enzyme activity, besides a decrease in transcript levels of NF-Ò¡B-p65 and caspase-1, indicating an overall inflammatory trend and an increase in the apoptotic shift. The co-administration of FA and/or treatment with LDR has ameliorated the hepatotoxic effect induced by CIS. The histopathological investigation of liver tissues confirmed this ameliorating action of these adjuvant therapies against CIS toxicity. In conclusion, it is plausible to suggest that the hepatoprotective effects of co-administration of FA and/or LDR against CIS-induced hepatotoxicity are attributed to the possession of anti-oxidative, anti-inflammatory, and anti-apoptotic capabilities.

Design and synthesis of novel quinazolinone-based derivatives as EGFR inhibitors with antitumor activity.

Nineteen new quinazolin-4(3H)-one derivatives 3a-g and 6a-l were designed and synthesised to inhibit EGFR. The antiproliferative activity of the synthesised compounds was tested in vitro against 60 different human cell lines. The most potent compound 6d displayed superior sub-micromolar antiproliferative activity towards NSC lung cancer cell line NCI-H460 with GI50 = 0.789 µM. It also showed potent cytostatic activity against 40 different cancer cell lines (TGI range: 2.59-9.55 µM). Compound 6d potently inhibited EGFR with IC50 = 0.069 ± 0.004 µM in comparison to erlotinib with IC50 value of 0.045 ± 0.003 µM. Compound 6d showed 16.74-fold increase in total apoptosis and caused cell cycle arrest at G1/S phase in breast cancer HS 578T cell line. Moreover, the most potent derivatives were docked into the EGFR active site to determine their binding mode and confirm their ability to satisfy the pharmacophoric features required for EGFR inhibition.

Haptoglobin polymorphism modulates cardiometabolic impacts of four consecutive weeks, dawn to sunset Ramadan intermittent fasting among subjects with overweight/obesity.

AIMS: Haptoglobin (Hp) is a multifaceted marker of inflammation, and mediates the interplay between obesity, inflammation, and cardiometabolic dysfunction. However, the role of the Hp phenotype in modulating intermittent fasting (IF)-induced cardiometabolic changes remains to be elucidated. METHODS: Hp phenotype was determined for the study subjects. Cardiometabolic markers were assessed before and at the end of four consecutive weeks, dawn to sunset IF. RESULTS: A total of 114 subjects (75 males and 39 females, 38.7 ± 11.7 years, body mass index (BMI) of 30.41 ± 5.09 kg/m2) were recruited. Hp2-2 (n = 55, 48.2 %) and Hp2-1 (n = 53, 46.5 %) were the predominant phenotypes. Significant reductions were observed in serum Hp, IL-6, TNF-α, triglycerides (TG), total cholesterol (TC), LDL, BMI, and fat mass (FM), while a significant elevation was observed in serum CD163, HDL, and IL-10 at the end of the IF month for the whole population. Based on the Hp polymorphism, significant decreases in Hp, BMI, FM, TG, LDL, and TNF-α, with significant increases in HDL and CD163 levels were observed among subjects with Hp2-2 and Hp2-1 phenotypes. A more pronounced reduction in FM was reported in subjects with Hp2-2 in comparison with Hp2-1. CONCLUSION: Hp gene polymorphism modulates IF-induced changes in cardiometabolic markers. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN18205186; https://trialsearch.who.int/?TrialID=ISRCTN18205186.