SYNTHESIS, ANTICANCER EVALUATION AND MOLECULAR MODELING OF SOME SUBSTITUTED THIAZOLIDINONYL AND THIAZOLYL PYRAZOLE DERIVATIVES

Objective: The present work aimed to synthesize some new substituted thiazoles incorporated to pyrazole moiety starting from 1-(3-chlorophenyl)-3-(4-methoxyphenyl)-1H-pyrazole-4-carboxaldehyde (1) in order to evaluate their anticancer activity and GSTP1 inhibition in a trail to explore new potential GST inhibitors and prevent the resistance of cells to anticancer drugs. In addition, investigate the probability of the most promising cytotoxic compounds to inhibit GSTP1 enzyme via molecular docking study.Methods: The carboxaldehyde 1 was treated with substituted thiosemicarbazide in absolute ethanol to give the corresponding thiosemicarbazone derivatives 2a–d. Cyclization of 2a-d either by ethyl bromoacetate, phenacyl bromide or maleic acid anhydride furnished new thiazole derivatives 3, 4 and 5, respectively. These target compound 2-5 were screened for their GSTP1 inhibition and cytotoxic activity against HEPG-2 (human liver carcinoma), A549 (human lung carcinoma) and PC3 (human prostate carcinoma). Finally, molecular docking study of the most promising cytotoxic compounds against GSTP1 (PDB ID: 3GUS) is discussed.Results: Compounds 4a, 4b, and 4d were found to be highly active against HEPG-2 and PC-3 cancer cell lines with IC50 values ranging from 0.2±0.81 to 9.3±2.08 μM compared to doxorubicin with IC50= 37.8±1.50 and 41.1±2.01 μM, respectively. Screening of 4a, 4b and 4d against GSTP1 showed higher inhibition activity with IC50 ranging from 1.5±0.18 to 4.3±0.29 μM. Docking studies revealed the promising binding affinities of the latter compounds which match with the binding mode of the ligand, NBDHEX toward the active site of GSTP1.Conclusion: Compounds 4a, 4b and 4d were distinguished by the higher anticancer activity against HEPG-2, A-549 and PC-3 cell lines of tumor and the remarkable inhibitory activity against GSTP1

PREPARATION AND EVALUATION OF CHEMICALLY INACTIVATED SALMONELLA ENTERITIDIS VACCINE IN CHICKENS

  Objective: Salmonella enteritidis ghosts (SEGs) is a non-living empty bacterial cell envelopes which were generated using a different concentration of sodium hydroxide (NaOH) 6.4 mg/mL and evaluated as a vaccine candidate in specific pathogen-free (SPF) chicken. SEGs have been produced by chemical-mediated lysis and evaluated the potential efficacy of chemically induced SEG vaccine and its ability to induce protective immune responses against virulent S. enteritidis challenge in SPF chickens.Methods: SPF chickens were divided into three groups: Group A (non-vaccinated control), Group B (vaccinated with prepared vaccine), and Group C (vaccinated with commercial vaccine).Results: Vaccination of SPF chicken with SEGs induced higher immune responses before and after virulent challenge. SPF chicken vaccinated with SEGs showed increasing in serum enzyme-linked immunosorbent assay (ELISA) antibodies. During the vaccination period, Groups B and C showed higher serum antibody titer compared to Group A. The minimal inhibitory concentration (MIC) of NaOH was capable of inducing non-living SEGs, and it has successfully generated non-living SEGs by MIC of NaOH.Conclusion: It is a one-step process which means easy manufacturing and low production cost compared to protein E-mediated lysis method. Chemically induced SEG vaccine is a highly effective method for inducing protective immunity. This study strongly suggests that SEGs will be a permissive vaccine, as the method of inhibition of S. enteritidis was safe and cheaper than other methods, and it gave a good protection

Synthesis of some new of thieno[2,3-b]pyridines, pyrazolo[1,5-a]pyrimidine, [1,2,4]triazolo[1,5-a]pyrimidine, pyrazolo[5,1-c]triazine and pyrimido[1,2-a]benzimidazole derivatives containing pyridine moiety

pyrazolo[1,5-a]pyrimidine, [1,2,4]triazolo[1,5-a]pyrimidine and pyrimido[1,2-a] benzimidazole derivatives were synthesized by reaction of sodium salt of 3-hydroxy-(1-pyridin-2-yl)prop-2-en-1-one or sodium salt of 3-hydroxy-1-(pyridin-3-yl)prop-2-en-1-one with different heterocyclic amines in piperidenium acetate. Also, 3-amino-6-(2-pyridyl)thieno[2,3-b]pyridine derivatives were synthesized via reaction of pyridine-2-thione with various halogenated compounds. The structures of the newly synthesized compounds were confirmed by elemental analysis, spectral data, X-ray and alternative synthetic routes whenever possible

Invasive fungal infections and patients with malignancies in upper Egypt

The incidence of invasive fungal infections has increased considerably in recent years. The aim of this study was to present a suitable early diagnostic procedure in immune compromised patients, using detection of fungal infection of urine samples collected from 33 patients with malignancies (from 2-89 years old), during the period from December 2012 to February 2014, from South Egypt. Fifty-three fungal species representing 14 genera were collected during this investigation from urine samples on Sabouraoud’s Dextrose Chloramphenicol Agar (46 species and 12 genera) and Rose Bengal Chloramphenicol Agar media (41 species and 11 genera). Aspergillus (16 species), Penicillium (14 species), Yeasts (5 species) and Cladosporium (5 species) contributed the broadest spectra of species in all samples tested on two types of media used. Other species were represented by 13 species belonging to 10 genera. The results indicate that immune compromised patient is a suitable habitat for the growth and sporulation of different groups of fungi, both saprophytic and pathogenic. A variety of types of filamentous fungi were obtained from malignancies patients. Immunosuppressant patient’s exposure for fungal infection so should be in especial care from food, drinking and air. Published by the International journal of Microbiology and Mycology (IJMM

Mechanisms of Photoisomerization and Water Oxidation Catalysis of Ruthenium(II) Aquo Complexes

Polypyridyl ruthenium(II) complexes have been widely researched as promising functional molecules. We have found unique photoisomerization reactions of polypyridyl ruthenium(II) aquo complexes. Recently we have attempted to provide insight into the mechanism of the photoisomerization of the complexes and distinguish between the distal−/proximal-isomers in their physicochemical properties and functions. Moreover, polypyridyl ruthenium(II) aquo complexes have been intensively studied as active water oxidation catalysts (WOCs) which are indispensable for artificial photosynthesis. The catalytic aspect and mechanism of water oxidation by the distal-/proximal-isomers of polypyridyl ruthenium(II) aquo complexes have been investigated to provide the guided thought to develop more efficient molecular catalysts for water oxidation. The recent progress on the photoisomerization and water oxidation of polypyridyl ruthenium(II) aquo complexes in our group are reviewed to understand the properties and functions of ruthenium complexes

Geochemical Evaluation of Heavy Metals (Cd, Cr, Fe, and Mn) in Sediment of Shatt Al-Basrah, Iraq

In this study, the sediment of Shatt Al-Basrah canal, was evaluated to illustrate the distribution of 4 heavy metals Cd, Cr, Fe and Mn in sediments collected from 5 sites. The assessment of heavy metals was conducted using three indices; the geoaccumulation index (I-geo), the enrichment factor (E.F.) and Pollution Index (PI). According to I-geo, the sediments collected from all sampling locations were unpolluted by Cd, Cr and Fe, where their values are less than 0 (<0), except Mn ranged between 0.98 to 1.37, the Igeo values for Mn show that sediments of Shatt Al-Basrah are unpolluted to moderately polluted for all sampling locations. Based on The enrichment factor, the sediment of Shatt Al-Basrah canal are classified as followed; significant enrichment for Cd, moderate enrichment to significant enrichment for Cr and deficiency to minimal enrichment for Mn. PI, which is based on individual metal Concentrations, shows that all sampling sites have no pollution effect for Cd, Cr and Mn, except Fe, which cause Slightly pollution affect in all site

Analysis of NPHS2 Gene Mutations in Egyptian Children with Nephrotic Syndrome

BACKGROUND: Mutations in the NPHS2 genes are the main aetiology of early-onset and familial steroid-resistant nephrotic syndrome (SRNS). The pathogenic NPHS2 mutation together with the p.R229Q variant has been less described among Egyptian children. AIM: This study aims to determine the mutation of NPHS2 in children with NS and discover the role of p.R229Q variant in SRNS METHODS: The study included 53 children with NS, and 53 healthy volunteers matched in age and sex controls. The median age at disease onset was 7.3 years. Among NS cases, 31 cases had steroid-sensitive nephrotic syndrome (SSNS) and 22 children with steroid-resistant nephrotic syndrome (SRNS). Polymerase chain reaction amplification of the whole coding region of NPHS2 gene was carried out for its mutational analysis. Restriction digestion testing was carried out after PCR to determine the presence of R229Q polymorphism. Randomly selected samples were re-genotyped by two independent technicians for assessment of Quality control RESULTS: NS patients showed a significant higher frequency of heterozygous genotype GA (89.5%) compared to control group (10.5%) with increased risk of NS (OR, 12.04; 95% CI, 2.61 to55.38; p &lt; 0.0001). Moreover, SRNS showed a significant higher frequency of GA genotype (68.2%) than the SSNS group (6.5%). The GA genotype was associated with increased risk of SRNS (OR, 31.1; 95% CI, 5.73 to 168.48; P &lt; 0.001) and the A allele was associated with increased risk of SRNS (OR, 15.52; 95% CI, 3.325 to 72.422; P &lt; .001). CONCLUSION: R229Q polymorphisms are associated with SRNS, and any child with SRNS should be searched for mutations in the NPHS2 gene

An integrative comparative study between ultrasound-guided regional anesthesia versus parenteral opioids alone for analgesia in emergency department patients with hip fractures: A systematic review and meta-analysis

BackgroundEmergency physicians play a major role in managing patients with hip fractures. The most commonly used pain management option is parenteral opioids. However, parenteral opioids are subjected to several adverse effects. New pain management techniques such as regional anesthesia are used as alternatives to parenteral opioids. Anatomical landmarks were used to administer regional anesthesia; however, ultrasound guidance has shown promising results with regional anesthesia. Objectiveof the Review: The present study compares the efficacy of ultrasound-guided regional anesthesia (USGRA) to parenteral opioids in analgesia of hip fractures patients. MethodsA literature search for original and relevant articles carried out through six electronic databases, yielded 710 articles which were then assessed using the eligibility criteria resulting in 8 studies eligible for inclusion. ResultsA Meta-analysis of the seven studies showed that ultrasound-guided femoral nerve block was more effective than parenteral opioids in relieving pain. Similarly, meta-analysis of data from two studies shows that US-guided FICB significantly reduced pain scores than parenteral opioids. A subgroup analysis of adverse events showed no significant difference in nausea/vomiting and respiratory complications. However, a subgroup analysis on hypotension showed that the incidence of hypotension was significantly lower in USGRA than parenteral opioids. The present study also revealed that patients in the USGRA group required less frequent rescue analgesia than the patients in the parenteral opioids group. ConclusionResults of the present study show that USGRA is superior to parenteral opioids in reducing pain and the need for rescue analgesia in patients with hip fractures.The publication of this article is funded by the Qatar National Library

Integrative analysis of WDR12 as a potential prognostic and immunological biomarker in multiple human tumors

Background: Mammalian WD-repeat protein 12 (WDR12), a family member of proteins containing repeats of tryptophan-aspartic acid (WD), is a potential homolog of yeast Ytm1p and consists of seven repeats of WD.Aim of the study: This study aims to investigate the potential oncogenic effects of WDR12 in various human malignancies throughout a pan-cancer analysis that has been carried out to examine the various patterns in which this gene is expressed and behaves in tumor tissues.Methods: Herein, we used The Cancer Genome Atlas (TCGA) and various computational tools to explore expression profiles, prognostic relevance, genetic mutations, immune cell infiltration, as well as the functional characteristics of WDR12 in multiple human cancers.Results: We found that WDR12 was inconsistently expressed in various cancers and that variations in WDR12 expression predicted survival consequences for cancer patients. Furthermore, we observed a significant correlation between WDR12 gene mutation levels and the prognosis of some tumors. Furthermore, significant correlations were found between WDR12 expression patterns and cancer-associated fibroblast (CAF) infiltration, myeloid-derived suppressor cells (MDSCs), tumor mutation burden, microsatellite instability and immunoregulators. Ultimately, pathway enrichment analysis revealed that WDR12-related pathways are involved in carcinogenesis.Conclusions: The findings of our study are stisfactory, demonstrating that WDR12 could serve as a promising reliable prognostic biomarker, as well as a therapeutic target for novel cancer therapeutic approaches

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London