Novel tetrazole and cyanamide derivatives as inhibitors of cyclooxygenase-2 enzyme: design, synthesis, anti-inflammatory evaluation, ulcerogenic liability and docking study

Nineteen new compounds containing tetrazole and/or cyanamide moiety have been designed and synthesised. Their structures were confirmed using spectroscopic methods and elemental analyses. Anti-inflammatory activity for all the synthesised compounds was evaluated in vivo. The most active compounds 4c, 5a, 5d–f, 8a and b and 9a and b were further investigated for their ulcerogenic liability and analgesic activity. Pyrazoline derivatives 9b and 8b bearing trimethoxyphenyl part and SO2NH2 or SO2Me pharmacophore showed equal or nearly the same ulcerogenic liability (UI: 0.5, 0.75, respectively), to celecoxib (UI: 0.50). Most of tested compounds showed potent central and/or peripheral analgesic activities. Histopathological investigations were done to evaluate test compounds effect on rat's gastric tissue. The obtained results were in consistent with the in vitro data on COX evaluation. Docking study was also done for all the target compounds inside COX-2-active site

Clinico-radiographic and histopathologic evaluation of iliac shaft fracture in dogs (an experimental study)

The pelvic region has a great importance as it is the connecting ring between the hind limbs and the trunk as well as having special shape. The present study was conducted on 15 adult, mongrel male dogs aged 2–3 years and weighted 15–20 kg. Iliac shaft fracture was induced experimentally, and the fractured ilium was fixed by Dynamic Compatable Plate (DCP). Fracture healing was evaluated clinically, radiologically and histopahologically. The animals were partially-weight bearing on the limb of operated side 4th day post-operatively and they were full-weight bearing within 17th days post-operatively. The gait was varied from occasional lameness to full function at the 21–28th post-operatively. The results of this study was conducted along 16 weeks confirmed that the internal fixation for fractured ilium using a bone plate and screws had a good fixation and healing and all animals returned to normal gait within short time. Keywords: Ilium, Canine, Experimental study, Histopatholog

Dual anticancer activity of Aspergillus nidulans pigment and Ionizing γ-Radiation on human larynx carcinoma cell line

Abstract Background Fungi are a readily available source of naturally generated colored compounds. These compounds might be used as radiosensitizers for treating cancer cells. Methods Aspergillus nidulans was examined for its color-producing ability in Potato dextrose agar (PDA) broth medium. The pigment was characterized by Ultraviolet (UV) spectrophotometer and Gas Chromatography Mass Spectrometry (GC/MS). Pigment extracts from A. nidulans were studied for their cytotoxic effects on the growth of human larynx carcinoma cell line (HEp-2) with or without exposure to γ-radiation at three different doses (5, 10, and 15 Gy). A. nidulans pigment cytotoxic activity was tested against normal Vero cells. Cell apoptosis was studied using flow cytometry. Gene expression of P53, Caspase 3 and Bcl-2 were quantified. Results Ultraviolet spectrum and GC/MS revealed the ability of Aspergillus nidulans to produce Rhodopin pigment. HEp-2 cells treated with A. nidulans pigment only give IC50 about 208 µg/ml. In contrast, when treated with the pigment +10 Gy γ-radiation, it give about 115 µg/ml. However, for normal cells, lower cytotoxic activity was detected. Treatment with pigment (208 g/mL) caused about 50% ± 1.0 total apoptosis level and gene expression of P53: 2.3 fold and Caspase 3: 1.84 fold in respect to untreated HEp-2), while Bcl-2 was decreased (Bcl-2: 0.63 fold in respect to untreated HEp-2). Furthermore, treated with pigment (115 µg/mL) + 10Gy caused about 47.41% ± 1.7 total apoptosis level and P53: 2.53 fold and Caspase 3: 2.0 fold in respect to untreated HEp-2, while Bcl-2 was downregulated (Bcl-2: 0.61 fold in respect to untreated HEp-2). Conclusion This study concluded that the anti-cancer activity of Aspergillus nidulans pigment was enhanced by ionizing radiation at 10 Gy, as well as its low cytotoxic activity against normal Vero cells

Parent-reported feeding characteristics in children with ASD vs. children who are typically developing

Abstract Background Parents of children with autism spectrum disorders (ASDs) often report that their children have multiple dietary behavior problems than parents of typically developing (TD) children do. This may affect proper nutrition and subsequently adequate growth and development in children with ASD. The current study aimed to assess the feeding behavior in recently diagnosed children with autism spectrum disorders (ASD) ranged in age from 2 to 4 years and compare it with typically developing (TD) children and to explore the relationship between feeding behaviors and autism severity using the Montreal Children’s Hospital Feeding Scale (MCH) and Childhood Autism Rating Scale (CARS), respectively. Parents of 35 preschool children (2–4 years) with ASD completed reports of physical measurements, feeding interview, Childhood Autism Rating Scale (CARS), and Montreal Children’s Hospital Feeding Scale (MCH Feeding-Scale). The collected data from parents of children with ASD were analyzed and compared with 70 typically developed children matched with age and sex. Results ASD children showed statistically significantly more problematic feeding behaviors in most of the assessed eating characters compared with TD children, e.g., food neophobia, eating non-food items instead of food, requiring assistance during eating, and feeding avoidance to particular textures and taste. The mean total score of the MCH feeding scale differed significantly between children with ASD and TD children. No correlation was found between the mean total score of the MCH feeding scale and CARS scores. Conclusion Our findings revealed a high rate of behavioral feeding problems in children with ASD. Future work will be needed to follow up the feeding behaviors and to develop practical feeding approaches for ASD children to maintain nutritional adequacy

Evaluation of the General Organization of Veterinary Services control program of animal brucellosis in Egypt: An outbreak investigation of brucellosis in buffalo

Background and Aim: Brucellosis is a major constraint to livestock production in Egypt as well as many developing countries worldwide. Bovine brucellosis is an economically important disease with reproductive failure as a principal manifestation resulting in abortion, premature birth and decreased milk production in females, and orchitis and epididymitis in males. In spite of the efforts of Egyptian veterinary services to overcome brucellosis, the disease is still prevalent in both animals and humans and represents one of the most important public health hazards in Egypt. The aim of the present work was to investigate the efficacy of the control program implemented by the General Organization of Veterinary Services in Brucella infected buffalo farm on serological, molecular, cultural, and histopathological basis. Brucella melitensis biovar 3 was recovered from 6 buffalo-cows. Materials and Methods: Blood samples were collected from a total of 750 non-vaccinated lactating buffalo-cows. These animals were proved positive for Brucella by the Egyptian brucellosis national program. Sera were tested using buffered acidified plate antigen test and rose Bengal test as screening tests and complement fixation test as a confirmatory test. Positive animals were separated for slaughtering under the supervision of the Egyptian veterinary authorities. Remaining animals were tested every 3 weeks with slaughtering of positive cases and this continued until the remaining animals revealed three successive negative serological tests. Different lymph nodes (prescapular, prefemoral, mediastinal, retropharyngeal, and supramammary) were collected from 11 Brucella seropositive buffalo-cows slaughtered after being confirmed serologically as Brucella infected cases. Samples were collected and processed for bacterial isolation and nucleic acid detection using polymerase chain reaction (PCR). Parts of these specimens were fixed in 10% neutral buffered formalin for 48 h then processed by paraffin embedding technique. Results: "Test and slaughter" policy was applied on Brucella infected dairy buffalo farm. The program continued for 6 months with slaughtering of positive cases until the herd was proved Brucella free. B. melitensis biovar 3 could be recovered from six buffalo-cows. Universal PCR confirmed Brucella on genus level and Bruce-ladder multiplex, PCR confirmed the presence of B. melitensis on the species level. Histopathological examination of Brucella-infected lymph nodes revealed massive rarified and depleted lymphoid areas of both sub-capsular and deep cortical lymphoid follicles, macrophage cells granulomatous reaction, as well as fat, infiltrates, and chronic vasculitis. The chronic nature of Brucella lesions has been confirmed in this study as indicated by the chronic vasculitis and collagen deposition. Conclusion: Freedom status from brucellosis in this study required 6 months which are considered long time allowing the spread of infection to other localities especially under unhygienic conditions, husbandry system favoring mixed populations of different ages, sex, aborted and pregnant, and lack of controlled movement of animals. Therefore, effective control of animal brucellosis requires surveillance to identify infected animal herds, elimination of the reservoirs, and vaccination of young heifers. B. melitensis biovar 3 is the cause of the Brucella outbreak in buffalo which still remains the prevalent type of Brucella in Egypt. The disease runs a chronic course allowing further spread of infection

Novel [(3-indolylmethylene)hydrazono]indolin-2-ones as apoptotic anti-proliferative agents: design, synthesis and in vitro biological evaluation

On account of their significance as apoptosis inducing agents, merging indole and 3-hydrazinoindolin-2-one scaffolds is a logic tactic for designing pro-apoptotic agents. Consequently, 27 hybrids (6a–r, 9a–f and 11a–c) were synthesised and evaluated for their cytotoxicity against MCF-7, HepG-2 and HCT-116 cancer cell lines. SAR studies unravelled that N-propylindole derivatives were the most active compounds such as 6n (MCF-7; IC50=1.04 µM), which displayed a significant decrease of cell population in the G2/M phase and significant increase in the early and late apoptosis by 19-folds in Annexin-V-FTIC assay. Also, 6n increased the expression of caspase-3, caspase-9, cytochrome C and Bax and decreased the expression of Bcl-2. Moreover, compounds 6i, 6j, 6n and 6q generated ROS by significant increase in the level of SOD and depletion of the levels of CAT and GSH-Px in MCF-7

<i>Nephthea</i> sp. inhibits biofilm, DNA gyrase, HSP90, and DHFR: <i>in vitro</i>, <i>in silico</i>, and pharmacokinetics studies

This study attempts to identify and assess a novel marine-derived antibiofilm agent. The antibacterial activity of n-hexane, dichloromethane, ethyl acetate, and butanol fractions from the crude extract of soft coral Nephthea sp. was evaluated against six microorganisms.Ethyl acetate fraction considered the most effective one against Bacillus subtilis, Escherichia coli, and Candida, investigated potential biofilm inhibition against the tested strains. Seventeen secondary metabolites were identified using (UPLC-Q/TOF-MS) responsible for these biological activities of the active fraction. Additionally, a molecular docking study showed free binding energy of −7.5 kcal/mol; Azamial A had the highest binding affinity for the DNA gyrase enzyme, while Sinularectin had −8.3 and −7.6 kcal/mol for the DHFR and HSP90 enzymes, respectively. Moreover, pharmacokinetics and (ADME) studies for Azamial A and Sinularectin were performed. Finally, results were confirmed by the in vitro enzymatic inhibitory effect of ethyl acetate fraction suggested in the in-silico study.</p

Synthesis of Natural Nano-Hydroxyapatite from Snail Shells and Its Biological Activity: Antimicrobial, Antibiofilm, and Biocompatibility

Hydroxyapatite nanoparticles (HAn) have been produced as biomaterial from biowaste, especially snail shells (Atactodea glabrata). It is critical to recycle the waste product in a biomedical application to overcome antibiotic resistance as well as biocompatibility with normal tissues. Moreover, EDX, TEM, and FT-IR analyses have been used to characterize snail shells and HAn. The particle size of HAn is about 15.22 nm. Furthermore, higher inhibitory activity was observed from HAn than the reference compounds against all tested organisms. The synthesized HAn has shown the lowest MIC values of about 7.8, 0.97, 3.9, 0.97, and 25 &micro;g/mL for S. aureus, B. subtilis, K. pneumonia, C. albicans, and E. coli, respectively. In addition, the HAn displayed potent antibiofilm against S. aureus and B. subtilis. According to the MTT, snail shell and HAn had a minor influence on the viability of HFS-4 cells. Consequently, it could be concluded that some components of waste, such as snail shells, have economic value and can be recycled as a source of CaO to produce HAn, which is a promising candidate material for biomedical applications

What Is behind the Correlation Analysis of Diarrheagenic <i>E. coli</i> Pathotypes?

The treatment failure recorded among patients and animals infected with diarrheagenic Escherichia coli (DEC) was increased due to the presence of specific virulence markers among these strains. These markers were used to classify DEC into several pathotypes. We analyzed the correlations between DEC pathotypes and antimicrobial resistances, the existence of virulence genes, serotypes, and hosts. The ETEC pathotype was detected with a high prevalence rate (25%). Moreover, the ETEC and EPEC pathotypes were highly associated with human infections in contrast to the EIEC and EAEC phenotypes, which were commonly recognized among animal isolates. Interestingly, the antimicrobial resistance was affected by E. coli pathotypes. With the exception of EIEC and STEC, imipenem represented the most effective antibiotic against the other pathotypes. There were fixed correlations between the DEC pathotypes and the presence of virulence markers and hosts; meanwhile, their correlation with serotypes was variable. Additionally, the vast majority of our isolates were highly diverse, based on both phenotypic and ERIC molecular typing techniques. Our promising results gave a clear indication for the heterogeneity and weak clonality of DEC pathotypes in Egypt, which can be utilized in the evaluation of the current therapeutic protocols and infection control guidelines

Optimization of Supercritical Carbon Dioxide Extraction of <i>Saussurea costus</i> Oil and Its Antimicrobial, Antioxidant, and Anticancer Activities

Saussurea costus is a medicinal plant with different bioactive compounds that have an essential role in biomedicine applications, especially in Arab nations. However, traditional extraction methods for oils can lead to the loss of some volatile and non-volatile oils. Therefore, this study aimed to optimize the supercritical fluid extraction (SFE) of oils from S. costus at pressures (10, 20, and 48 MPa). The results were investigated by GC/MS analysis. MTT, DPPH, and agar diffusion methods assessed the extracted oils’ anticancer, antioxidant, and antimicrobial action. GC/MS results showed that elevated pressure from 10 to 20 and 48 MPa led to the loss of some valuable compounds. In addition, the best IC50 values were recorded at 10 MPa on HCT, MCF-7, and HepG-2 cells at about 0.44, 0.46, and 0.74 μg/mL, respectively. In contrast, at 20 MPa, the IC50 values were about 2.33, 6.59, and 19.0 μg/mL, respectively, on HCT, MCF-7, and HepG-2 cells, followed by 48 MPa, about 36.02, 59.5, and 96.9 μg/mL. The oil extract at a pressure of 10 MPa contained much more of á-elemene, dihydro-à-ionone, patchoulene, á-maaliene, à-selinene, (-)-spathulenol, cedran-diol, 8S,13, elemol, eremanthin, á-guaiene, eudesmol, ç-gurjunenepoxide-(2), iso-velleral, and propanedioic acid and had a higher antioxidant activity (IC50 14.4 μg/mL) more than the oil extract at 20 and 48 MPa. In addition, the inhibitory activity of all extracts was higher than gentamicin against all tested bacteria. One of the more significant findings from this study is low pressure in SFE enhancement, the extraction of oils from S. costus, for the first time. As a result, the SFE is regarded as a good extraction technique since it is both quick and ecologically friendly. Furthermore, SFE at 10 MPa increased the production and quality of oils, with high antioxidant activity and a positive effect on cancer cells and pathogens