Design, synthesis, and anticancer evaluation of N-sulfonylpiperidines as potential VEGFR-2 inhibitors, apoptotic inducers.

A new panel of N-sulfonylpiperidine derivatives has been designed and synthesized as vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors. Anti-proliferative activities of the synthesized members were tested against colorectal carcinoma (HCT-116), hepatocellular carcinoma (HepG-2), and breast cancer (MCF-7) cell lines. Compounds 3a, 4, 8, and 9 showed the highest activities against the tested cell lines. In particular, compound 8 showed excellent activities against HCT-116, HepG-2, and MCF-7 with IC50 values of 3.94, 3.76, and 4.43 µM, respectively. Such IC50 values are comparable to vinblastine (IC50 = 3.21, 7.35, 5.83 µM, respectively) and doxorubicin (IC50 = 6.74, 7.52, 8.19 µM, respectively). In vitro VEGFR-2 inhibitory activity of the most promising molecules (3a, 4, 8, and 9) indicated that compound 8 is the highest VEGFR-2 inhibitor with an IC50 of 0.0554 µM, compared to sorafenib (IC50 = 0.0416 µM). The most promising candidates (3a, 4, 8, and 9) were subjected to flow cytometry analyses to assess their effects on the cell cycle behavior and the apoptotic power against the three tested cell lines (HCT-116, HepG-2, and MCF-7). The tested compound arrested the tumor cells at both the G2/M and Pre-G1 phases. In addition, compound 9 was proved as the most effective apoptotic inducer among the tested compounds against the tested cells. Molecular docking studies against VEGFR-2 (PDB ID: 2OH4) revealed good binding modes of the synthesized compound similar to that of sorafenib. Computational investigation of ADMET parameters revealed the drug-likeness of the synthesized compounds.

Improving productive performance, immunity, and health status of growing rabbits by using honey bee venom (Apis mellifera).

To investigate the effect of bee venom (BV) as a natural growth promotor on growing rabbits as an alternative to antibiotics, sixty 35-day-old Californian male rabbits with an average body weight of 584 ± 9 gm were randomly divided into five equal groups as follows: The 2nd group received drinking water supplied with 10 mg Oxytetracycline (OXT), while the 3rd, 4th, and 5th groups received 2, 4 and 8 mg bee venom (BV)/kg body weight/day in drinking water, and the first group was served as a control group. The growth performance features were positively impacted by adding BV (p ≤ 0.01) compared to the control, whereas LBW and BWG increased and FI reduced. Significantly improved carcass characteristics (p ≤ 0.01) as a result of the BV supplementation. Blood characteristics showed a significant reduction (p ≤ 0.01) in liver enzyme activities and Cholesterol, Triglycerides, and Low-density lipoproteins Cholesterol (LDL) as affected by BV treatment; inversely, total protein and globulin were significantly increased (p ≤ 0.01). Similarly, BV had a positive effect (p ≤ 0.01) on anti-oxidant status (Total anti-oxidant capacity (TAC), Glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT)). In contrast, the lipid peroxidation biomarker (Malondialdehyde (MDA)) was significantly decreased. The immunoglobulin (IgG and IgM) was significantly increased (p ≤ 0.01) by BV treatment. There was a positive effect of low BV levels on decreasing both cecum TBC and pathogenic bacterial count (Salmonella spp., E.coli spp., Proteus spp., and Clostridia spp.) that was significant (p ≤ 0.01). In conclusion, BV can be a natural growth promoter to enhance growth performance traits, immunological and anti-oxidative responses, and reduce pathogenic bacteria in the hindgut of growing rabbits.

In-Ovo injection of melittin into Alexandria chicken eggs: a way for early immune acceleration.

This study intended to assess the properties of in-ovo administration of Melittin (MLT) on hatchability, chick yield, hematology, immunological indices and relative organs weight of Alexandria chickens at hatch. A total of 600 eggs with an average weight of (45.12 g), were gathered and split into five groups: a non-injected group or negative control (NC), a saline injection group or positive control (PC), and three concentrations of MLT (5, 10 and 15 µg of MLT per egg, respectively). On day 18 of incubation, eggs from the injection groups were injected into the amniotic fluid from the large end with the in-ovo injection solutions (0.2 ml per egg). Results indicated that 10 µg MLT/egg positively affected the weight and yield of chicks. In addition, our findings indicated that the in-ovo administration with 10 or 15 µg MLT/egg was superior in most of the immunological indicators (spleen and bursa relative weights, immunoglobulins IgG and IgM, T cells and B cells). In conclusion, in order to improve the immune efficiency (early immune acceleration) of Alexandria chicks, which may contribute to offering a significant boost to their future performance, this study suggests injecting eggs with 5 or 10 µg MLT/egg.

Synthesis, description, and application of novel corrosion inhibitors for CS AISI1095 in 1.0 M HCl based on benzoquinoline derivatives.

This study aims to synthesize and evaluate the corrosion inhibition properties of three newly prepared organic compounds based on benzo[h]quinoline hydrazone derivatives. The compounds structure were characterised using FTIR, 1H-NMR, 13C-NMR and Mass spectroscopy. Electrochemical methods, including Potentiodynamic Polarization (PP), Electrochemical Frequency Modulation (EFM), and Electrochemical Impedance Spectroscopy (EIS) were employed to evaluate the compounds as corrosion inhibitors in HCl (1.0 M) for carbon steel (CS). Additionally, surface examination techniques such as scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) were used to investigate the surface morphology and elemental composition of the CS before and after exposure to the synthesized compounds. The electrochemical measurements showed that compound VII achieved corrosion inhibition efficiency. SEM and EDX analysis further confirmed the creation of a passive film on the CS surface. These findings demonstrated the potential of benzo[h]quinoline hydrazone derivatives as effective organic corrosion inhibitors for CS in aggressive solution.

Impact of dietary vitamin (E) and Eruca sativa seeds powder on broiler productivity, health, carcass characteristics, and meat quality.

This investigation examined the impact of nutritional vitamin E (VE) and Eruca sativa seeds powder (ESSP) on broilers' performance, physiological, and meat quality. A total of 350 two-day-old Arbor Acres broiler chicks were used in this study. Chicks were allocated into five dietary treatments as follows: control (fed a basic diet), VE treatment (fed a basic diet supplemented with 150 mg/kg diet), the third, fourth, and fifth treatments were fed a basic diet supplied by different levels of ESSP (0.1, 0.2 and 0.4 g/kg diet). Outcomes showed that chicks of VE treatment or ESSP (0.2 g/kg) significantly improved vital body weight (BW), body weight gain (BWG) and feed conversion ratio (FCR). Additionally, relevant dressing and hind parts of the carcass for birds of VE treatment or ESSP at different levels were significantly increased. The results showed a significant improvement in meat quality traits. Moreover, ESSP (0.1 and 0.2 g/kg) groups represented a significant decrease in the total bacterial count and E. coli compared with other groups. In conclusion, ESSP positively affected broiler performance, hematological, and immunological indices, carcass characteristics, intestinal bacterial count, meat quality, and cooking properties of the resulting meat, especially at the level of (0.2 g/kg).

Blood hematology and biochemical of four laying hen strains exposed to acute heat stress.

This study is aimed at defining physiological responses to heat stress (HS) in four different lines to better understand the underlying mechanisms of various responses in these genotypes when exposed to heat for a short period. At the age of 30 weeks, 176 laying hens (44 each from the Fayoumi, Golden Sabahia, White Leghorn, and Lohman Brown) were allotted to 2 groups (thermoneutral temperature (26.0 ± 1 °C) and HS (35 ± 1 °C) with relative humidity 55 ± 5% for 6 h/day). Blood samples were collected after 6 h of heat. According to the findings of this study, acute HS increased the concentration of LH in hens by 20.2% while decreasing the concentration of FSH by 4.24. Genotype was found to have a significant effect on blood hematology and most blood biochemical. Significant differences were found between heat stress and genotype in most of the blood parameters. Golden sabahia laying hens had significantly higher WBC, IgY, and LH levels than other groups under HS. The findings of the current study suggested that Lohman Brown was less tolerant to acute HS than another genotype.

Influence of hot red pepper oil in broiler diets on blood, antioxidant, immunological parameters and intestinal bacteria counts.

The present study aimed to examine the impacts of supplementing hot red pepper oil (HRPO) to broiler diets. One hundred and twenty Arbor Acres chicks were divided randomly into four experimental groups as three supplementation levels of HRPO (0.25, 0.5 and 1.0 mL/kg diet) and the control group. Results showed that HRPO supplementation exhibited significantly (p < 0.001) higher red blood cells (RBCs) count, hemoglobin (Hb) and packed cells volume (PCV) percentage, while insignificant effects were shown for white blood cells (WBCs) count or its differentiation. Diets supplemented with different levels of HRPO influenced significantly (p < 0.001) the total protein (TP), albumin (Alb) and glucose (Glo) values of the studied birds. Results also indicated that different levels of HRPO supplementations significantly (p < 0.01) decreased total lipid, triglycerides (Trig), cholesterol (Cho) and low-density lipoprotein (LDL), but did not affect high density lipoprotein (HDL) values. Data revealed that supplementing broiler diets with different levels of HRPO enhanced their liver function. The bactericidal activity index was significantly increased (p < 0.02) compared with control. HRPO supplemented groups had beneficial effects (p < 0.02) on cecal microbiota count. It could be concluded that dietary HRPO supplementation could improve the general internal health status of Arbor Acres broiler chicks.

Transcatheter aortic valve implantation-related infective endocarditis: experience from an Irish tertiary referral centre.

BACKGROUND: Transcatheter aortic valve implantation-related infective endocarditis (TAVI-IE) is a well-recognised and serious complication following TAVI. The purpose of this study was to describe the clinical characteristics, microorganism spectrum, and outcomes of TAVI-IE in an Irish context. METHODS: A prospective registry was used to assess the baseline demographics, procedural variables, and clinical outcomes of patients undergoing TAVI between 2009 and 2020 at two tertiary referral Irish Hospitals. RESULTS: A total of 733 patients underwent TAVI during the study period. During a follow-up duration of 1,949 person-years (median 28 months), TAVI-IE occurred in 17 (2.3%) patients. The overall incidence was 0.87 per 100 person-years and the median time from TAVI to presentation with IE was 7 months [IQR: 5-13 months]. In those who developed TAVI-IE, the mean age was 78.7 years, 70.5% were male, and there was a trend towards more permanent pacemaker implantations post-TAVI (17.6% vs. 5.86%; p = 0.08). The dominant culprit microorganisms were streptococci (41.1%) and four (23.5%) cases were attributed to dental seeding. Major complications of TAVI-IE included one (5.8%) stroke, one (5.8%) in-hospital death, and two (11.7%) urgent surgical aortic valve replacements. The Kaplan-Meier estimate of survival at 1-year was 82% (95% CI = 55-95). CONCLUSIONS: This Irish cohort of TAVI-IE exhibited a similar incidence and time to presentation compared to prior international registries; however, the 1-year mortality rate was comparatively lower. The need for rigorous dental clearance pre-TAVI and maintenance of dental health post-TAVI is underscored by the high prevalence of oral streptococcus species in this cohort.

Performance traits and selected blood constituents of broiler chicks as influenced by early access to feed post-hatch.

The present study aimed to investigate the effect of early access to feed and water post-hatch on broiler chicks' performance. One hundred and twenty chicks were transferred from the hatchery to the rearing house and randomly divided into two groups. The first group: chicks were immediately access to feed and water (F-time 0). The second group: was held without feed and water for 24 h (F-time 24). Then, feed and water were provided ad-libitum, for both groups until 35 days of age. Results indicated that F-time 0 increased body weight and body weight gain throughout the experimental period. It increased feed intake during all experimental periods except from (22-28 days). Additionally, the F-time 0 enhanced the European production efficiency factor index. The F-time 24, increased red blood cells (RBCs) count, hemoglobin (HGB), and packed cell volume (PCV) percentage after 24 h. However, the F-time 0 had a higher RBCs count, HGB, and PCV at 35 days of age. F-time 24 increased total plasma protein, albumin, cholesterol, and triglycerides, after 24 h. In conclusion, early access to feed and water post-hatch enhances broiler chicks' performance and productivity and increases producers' revenue.

New thiadiazole modified chitosan derivative to control the growth of human pathogenic microbes and cancer cell lines.

The emergence of multidrug-resistant microbes and the propagation of cancer cells are global health issues. The unique properties of chitosan and its derivatives make it an important candidate for therapeutic applications. Herein, a new thiadiazole derivative, 4-((5-(butylthio)-1,3,4-thiadiazol-2-yl) amino)-4-oxo butanoic acid (BuTD-COOH) was synthesized and used to modify the chitosan through amide linkages, forming a new thiadiazole chitosan derivative (BuTD-CH). The formation of thiadiazole and the chitosan derivative was confirmed by FT-IR, 1H/13C-NMR, GC-MS, TGA, Elemental analysis, and XPS. The BuTD-CH showed a high antimicrobial effect against human pathogens Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, and Candida albicans with low MIC values of 25-50 µg ml-1 compared to unmodified chitosan. The in-vitro cytotoxicity of BuTD-CH was evaluated against two cancer cell lines (MCF-7 and HepG2) and one normal cell (HFB4) using the MTT method. The newly synthesized derivatives showed high efficacy against cancerous cells and targeted them at low concentrations (IC50 was 178.9 ± 9.1 and 147.8 ± 10.5 µg ml-1 for MCF-7 and HepG2, respectively) compared with normal HFB4 cells (IC50 was 335.7 ± 11.4 µg ml-1). Thus, low concentrations of newly synthesized BuTD-CH could be safely used as an antimicrobial and pharmacological agent for inhibiting the growth of human pathogenic microbes and hepatocellular and adenocarcinoma therapy.

Continuous positive airway pressure therapy suppresses inflammatory cytokines and improves glucocorticoid responsiveness in patients with obstructive sleep apnea and asthma: A case-control study.

CONTEXT: Asthma and obstructive sleep apnea (OSA) are prevalent respiratory disorders that frequently coexist. Continuous positive airway pressure (CPAP) therapy is the standard treatment for OSA. However, its effects on systemic inflammation and glucocorticoid responsiveness in OSA patients with asthma are largely unknown. AIMS: To examine the potential role of CPAP therapy in reducing systemic inflammation and improving glucocorticoid responsiveness in asthmatic patients with OSA. SETTINGS AND DESIGN: A case-control study was conducted at the respiratory and sleep clinics involving patients with OSA and patients with asthma and OSA. METHODS: The levels of inflammatory asthma biomarkers (interleukin [IL]-4, IL-17A, IL-8, IL-2, and interferon-γ [IFN-γ]), and glucocorticoid receptors (GR)-α and GR-ß, were determined to compare systemic inflammation and glucocorticoid responsiveness between pre- and post-1-month CPAP treatment in both groups. STATISTICAL ANALYSIS: The Wilcoxon signed-rank test was used to compare inflammatory biomarkers before and after CPAP therapy. P < 0.05 considered statistically significant. The analysis was performed using SPSS. RESULTS: Recruited patients (n = 47), 51% (n = 24) had OSA and 49% (n = 23), had OSA with asthma. Interestingly, the blood levels of IL-17 and IL-8 were significantly decreased post-CPAP therapy in OSA patients, whereas IL-4, IL-17, and IFN-γ were significantly reduced post-CPAP treatment in OSA patients with asthma. Remarkably, CPAP therapy improved glucocorticoid responsiveness in asthmatic patients with OSA, but not in the OSA group and an increase in the GR-α/GR-ß ratio was noted post-CPAP therapy. CONCLUSIONS: Continuous positive airway pressure therapy improved responsiveness to glucocorticoid treatment and demonstrated a suppressive effect on proinflammatory cytokines in asthmatics with OSA.

Synthesis and characterization of new functionalized chitosan and its antimicrobial and in-vitro release behavior from topical gel.

Recently, chitosan and its derivatives have been gaining more attention due to their high integration into various biomedical applications. Herein, a new chitosan derivative was prepared by linking the chitosan (Cs) with a novel heterocyclic compound, Benzoimidazolyl-thiadiazole (BzimTD) to form Cs-BzimTD. The synthesis of the new chitosan derivative was confirmed by Fourier-Transform Infrared (FT-IR) spectroscopy, proton nuclear magnetic resonance (1H NMR), thermogravimetric (TGA-DTG) analysis, elemental analysis, and UV-Visible spectrophotometer. Data showed the high efficacy of functionalized Cs-BzimTD to inhibit the growth of pathogenic microbes, Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans, with inhibition zones of 15.3 ± 0.6 - 9.2 ± 0.3 mm. Also, Cs-BzimTD was applied in a topical gel formulation by using two different polymers, Carbopol 940 (CP) and Carboxymethyl Cellulose (CMC) to form three gel formulations: Cs-BzimTD-CP, Cs-BzimTD-CMC, and Cs-BzimTD-CP-CMC. The new gels were checked for physical appearance, viscosity, Cs-BzimTD release, pH, spread-ability, and drug content. The results showed that all formulations were clear, transparent, and homogeneous with non-irritant pH values for skin (6.4 - 6.8). The spread-ability was found in the range of 7.1 - 9.4 g.cm/s. The Cs-BzimTD-CP formula showed the maximal Cs-BzimTD content percentage (86.5%) and the Cs-BzimTD release varied from 89.9 to 81.6% after 8 h depending on the gel formulation, with a maximum release achieved for Cs-BzimTD-CMC.

Stocking density: a clue for improving social behavior, welfare, health indices along with productivity performances of quail (Coturnix coturnix)-a review.

The quail populations are considered to be one of the largest among the poultry species. Although quail egg and meat production are growing rapidly, still, quail farming practices and welfare aspects are not well established. Stocking density is one of the factors that can significantly affect the welfare, health, and performance of birds, but according to The Expert Group for Technical Advice on Organic Production, no allowed space standards have been reported for new hybrids and different breeds of quail. This review presents an overview of 1) the benefits of egg and meat of quail, 2) the global market of quail products, 3) the factors affecting the stocking density rate, and 4) the effects of stocking density rates and housing systems on the social behavior, welfare, physiological indices, and performance parameters of broiler and laying quail. Conclusively, larger space and enriched aviaries reduce aggressive behavior, and improve the quail welfare and immunological indices. However, the effect of stocking density on some blood biochemical indices and growth performance parameters showed mixed results. A better understanding of the relationship between housing, health, growth performance, and welfare aspects would assist in the implementation of welfare-economic standards for quail production. According to available data, stocking density ranges for broiler and laying Japanese quail are suggested; however, these stocking rates should be tested under different conditions.

Outcomes of Percutaneous Coronary Intervention in Patients with Spontaneous Coronary Artery Dissection.

OBJECTIVES: To compare outcomes of percutaneous coronary intervention (PCI) in spontaneous coronary artery dissection (SCAD) patients versus conservative therapy. BACKGROUND: SCAD is an important cause of myocardial infarction (MI) in young-to-middle-aged women. Percutaneous coronary intervention (PCI) is often pursued, but outcomes compared to conservative therapy are unclear. METHODS: 403 nonatherosclerotic SCAD patients were enrolled between 2011 and 2017 and prospectively followed up in our Vancouver General Hospital registries. Detailed baseline, hospital, PCI, and outcomes were recorded. We explored the outcomes of SCAD patients who underwent PCI during their initial presentation. RESULTS: PCI was performed in 75 patients, the average age was 48.9 ± 10.1 yrs, and 94.7% were women. All presented with MI; 50.7% STEMI, 49.3% NSTEMI, and 13.3% had VT/VF. PCI was successful in 34.7%, partially successful in 37.3%, and unsuccessful in 28.0%. Stents were deployed in 73.3%, 16.0% had balloon angioplasty alone, 10.7% had wiring attempts only, and 5.3% required bailout surgery. Major adverse cardiovascular event rates (MACE) were significantly higher with the PCI group in hospital (29.3% versus 2.8%, p < 0.001), and at median follow-up of 3.7 yrs (58.7% versus 22.6% (p < 0.001) compared to the non-PCI group. CONCLUSION: PCI in SCAD patients was associated with high failure rate and MACE in hospital and at long-term follow-up. These findings support the recommendation of conservative therapy as first-line management unless high-risk features are present.

Antidiabetic effects of novel ellagic acid nanoformulation: Insulin-secreting and anti-apoptosis effects.

Antioxidants are one of the effective treatment lines in managing type 2 diabetes (typ2diab) and its complications. Nanoformulations could help in ameliorating the oral bioavailability and biocompatibility properties. Ellagic acid (Ella) is a natural antioxidant compound commonly present in fruits. This study examined the effect Ella nanoparticles (Ella NPs) alone and combined with metformin, the standard antidiabetic drug, on controlling blood glucose in typ2diab. Forty-eight adult Sprague-Dawley rats were used in this study. Except for the control group that was fed a regular pellet diet, all animals were fed a high-fat diet (HFD) for 9 weeks. For the last 4 weeks, rats were injected with streptozotocin (35 mg/kg). Then the rats were randomized into 8 groups: control, HFD, diabetic, Ella, Ella + metformin, Ella NPs, and Ella NPs + metformin. Data showed that Ella NPs improved blood glucose levels and the body weights of diabetic rats throughout all the weeks of the experiment whereas effects of the regular Ella were limited to the last two weeks of the treatment. Additionally, data demonstrated that the antidiabetic action of Ella NPs and its effective duration were similar to metformin. Ella NPs led to a lowering effect on lipid profile markers (total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL)), superior to the regular Ella, which reduced only TG and VLDL. Results of the pathological examination showed improved number and activity of beta islets in all treatment groups. The most enhanced islets were in the Ella NPs and metformin group. The different treatments decreased caspase 3 and increased insulin gene expression, and the effect was superior in the Ella NPs and metformin group. The results of this study confirmed that Ella could manage typ2diab by lowering glucose and lipid levels and improving body weight with the superiority of Ella NPs. The mechanisms behind these effects are inhibition of beta-cell apoptosis and stimulation of insulin production.

Synthesis, anticancer evaluation and molecular docking studies of new heterocycles linked to sulfonamide moiety as novel human topoisomerase types I and II poisons.

A series of heterocyclic compounds with a sulfonamide moiety were synthesized from reaction of enaminone 4 with active methylene compounds, glycine derivatives, 1,4-benzoquinone, hydroxylamine hydrochloride, hydrazonyl halides and dimethylacetylenedicarboxylate. The newly synthesized sulfonamide derivatives were characterized by FT-IR, 1H NMR, 13C NMR, mass spectroscopy, elemental analysis and alternative synthetic routes. The reactions products were evaluated for their antiproliferative activity against a panel of three different human cancerous cell lines, MCF-7 (breast), HepG-2 (liver) and HCT-116 (colon) and the results were deployed to derive the structure-activity relationships (SAR). Various test compounds were potent antiproliferative to cancerous cells; reaching very low micromolar levels, as in case of 21 which showed IC50 value of 6.2 µM against HepG-2 cell. In addition, treatment of cancerous cells with the synthesized compounds induced cell apoptosis and G2/M phase arrest evidenced by flow cytometric analysis. Furthermore, the activity of the synthesized compounds against TOP I and II were documented by DNA relaxation assays. Data revealed that compound 24 significantly interfered with TOP I- and II-mediated DNA relaxation, nicking and decatenation, with IC50 values 27.8 and 33.6 µM, respectively. Moreover, the molecular docking studies supported the results from enzymatic assays, where compound 24 was intercalated between nucleotides flanking the DNA cleavage site via pi-pi stacking and hydrophobic interactions. In conclusion, aromatic heterocycles linked to sulfonamides are excellent molecular frameworks amenable for optimization as dual TOP I and II poisons to control various human malignancies.

Rational Design and Synthesis of Diverse Pyrimidine Molecules Bearing Sulfonamide Moiety as Novel ERK Inhibitors.

Protein kinases orchestrate diverse cellular functions; however, their dysregulation is linked to metabolic dysfunctions, associated with many diseases, including cancer. Mitogen-Activated Protein (MAP) kinase is a notoriously oncogenic signaling pathway in human malignancies, where the extracellular signal-regulated kinases (ERK1/2) are focal serine/threonine kinases in the MAP kinase module with numerous cytosolic and nuclear mitogenic effector proteins. Subsequently, hampering the ERK kinase activity by small molecule inhibitors is a robust strategy to control the malignancies with aberrant MAP kinase signaling cascades. Consequently, new heterocyclic compounds, containing a sulfonamide moiety, were rationally designed, aided by the molecular docking of the starting reactant 1-(4-((4-methylpiperidin-1-yl)sulfonyl)phenyl)ethan-1-one (3) at the ATP binding pocket of the ERK kinase domain, which was relying on the molecular extension tactic. The identities of the synthesized compounds (4-33) were proven by their spectral data and elemental analysis. The target compounds exhibited pronounced anti-proliferative activities against the MCF-7, HepG-2, and HCT-116 cancerous cell lines with potencies reaching a 2.96 µM for the most active compound (22). Moreover, compounds 5, 9, 10b, 22, and 28 displayed a significant G2/M phase arrest and induction of the apoptosis, which was confirmed by the cell cycle analysis and the flow cytometry. Thus, the molecular extension of a small fragment bounded at the ERK kinase domain is a valid tactic for the rational synthesis of the ERK inhibitors to control various human malignancies.

Effects of supplementing broiler diets with coriander seed powder on growth performance, blood haematology, ileum microflora and economic efficiency.

A total of 480 one-day-old Arbor Acres broiler chicks were randomly assigned to four dietary groups, each including six replicates (n = 20/replicate). Broilers in the first group (G1) were fed a basal diet without any additives (control). Broilers in groups 2, 3 and 4 (G2, G3 and G4) were fed a basal diet supplemented with 0.1%, 0.2% and 0.4% coriander (Coriandrum sativum L.) seed powder (CSP) respectively. Feeding trials lasted for 42 days, and after that growth, carcass traits, haematological parameters, gut microbiota and economic efficiency (EE) were evaluated. Final body weight (FBW), total weight gain (TWG), total feed intake (TFI) and red blood cell (RBC) counts of broilers in the G4 and G3 treatment groups were significantly higher (p < .05) compared with broilers in the G1 treatment group. The feed conversion ratio (FCR) was better (p < .05) in the G4 treatment group (1.72) than in the G1 treatment group (1.84). Broilers in CSP treatment groups had significantly higher haemoglobin (Hb) concentrations, packed cell volume (PCV) and platelet counts, and had lower (p < .05) Escherichia coli and Clostridium perfringens counts compared with broilers in the G1 treatment group. Dressing, liver, pancreas, bursa and thymus percentages were higher (p < .05) in broilers in the G4 (70.30, 3.18, 0.31, 0.10 and 0.32% respectively) treatment group, compared with broilers in the control (G1) group (66.57, 2.37, 0.23, 0.04 and 0.21% respectively). Broilers in treatment groups G4 and G3 had lower percentages of abdominal fat and lower total bacterial counts (p < .05) than broilers in treatment groups G2 and G1. The highest economic efficiency (EE) was found in treatment group G4, and EE in this group was 13.06% greater than in the control (G1) group.

Natural History of Spontaneous Coronary Artery Dissection With Spontaneous Angiographic Healing.

OBJECTIVES: Given the uncertainty regarding the degree and prevalence of spontaneous healing following spontaneous coronary artery dissection (SCAD), the aim of this study was to assess the angiographic characteristics of the dissected segments in a large cohort of patients with SCAD who underwent subsequent repeat coronary angiography. BACKGROUND: SCAD is an uncommon yet important cause of myocardial infarction in women. Very little is known about the characteristics of healing of dissected arteries. METHODS: Patients with nonatherosclerotic SCAD followed prospectively at Vancouver General Hospital who underwent repeat angiography were included in this study. Those who underwent percutaneous coronary intervention for SCAD were excluded. Baseline patient demographics and in-hospital and long-term cardiovascular events were recorded. Angiographic characteristics of the SCAD artery at index and repeat angiography were assessed by 2 experienced angiographers. Criteria for angiographic healing were as follows: 1) improvement of stenosis severity from index event; 2) residual stenosis <50%; and 3) TIMI (Thrombolysis In Myocardial Infarction) flow grade 3. RESULTS: One hundred fifty-six patients with 182 noncontiguous SCAD lesions were included. The mean age was 51.5 ± 8.7 years, 88.5% were women, 83.3% were Caucasian, and 75.6% had fibromuscular dysplasia. All patients presented with myocardial infarction. At index angiography, type 2 SCAD was most commonly observed, in 126 of 182 lesions (69.2%); TIMI flow grade <3 was present in 85 of 182 (46.7%); and median lesion stenosis was 79.0% (interquartile range: 56.0% to 100%). Median time to repeat angiography was 154 days (interquartile range: 70 to 604 days), with median residual lesion stenosis improving to 25.5% (interquartile range: 12.0 to 38.8 days), and TIMI flow grade <3 observed in 10 of 182 lesions (5.5%). Angiographic healing occurred in 157 of 182 lesions (86.3%). Of repeat angiography performed ≥30 days post-SCAD, 152 of 160 (95%) showed spontaneous angiographic healing. CONCLUSIONS: The majority of coronary arteries affected by SCAD heal spontaneously on repeat angiography, with apparent time dependency, with the vast majority having complete healing after 30 days from the SCAD event.