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        Murraya koenigii (L.) Sprengel seeds and pericarps in relation to their chemical profiles: new approach for multidrug resistant Acinetobacter baumannii ventilator-associated pneumonia

        El-Shiekh Riham A.,Elshimy Rana,Mandour Asmaa A.,Kassem Hanaa A. H.,Khaleel Amal E.,Alseekh Saleh,Fernie Alisdair R.,Salem Mohamed A. 한국응용생명화학회 2024 Applied Biological Chemistry (Appl Biol Chem) Vol.67 No.-

        Acinetobacter baumannii is without a doubt one of the most problematic bacteria causing hospital-acquired nosocomial infections in today’s healthcare system. To solve the high prevalence of multi-drug resistant (MDR) in A. baumannii, we investigated one of the medicinal plants traditionally used as antibacterial agent; namely Murraya koenigii (L.) Sprengel. The total methanolic extracts of seeds and pericarps were prepared and their anti-bacterial activity was assessed using the agar diffusion method and minimum inhibitory concentration (MIC) was then calculated as compared to tigecycline. Then, an in-vivo murine model was established which confirmed the promising activity of M. koenigii seeds in demonstrating anti-bacterial and anti-inflammatory actions. The histopathological study of lungs, scoring of pulmonary lesions, counting of bacterial loads after infection by multi-drug resistant A. baumannii all provided evidence to support these findings. LC–MS/MS profiling coupled to molecular networking and chemometrics detected the presence of carbazole alkaloids, and coumarins as dominate metabolites of the active seed extracts. Positively correlated metabolites to antibacterial potential were 6-(2ʹ,3ʹ-dihydroxy-3-methylbutyl)- 8-prenylumbelliferone, scopoline, and 5-methoxymurrayatin. An in-silico study was also performed on the crystal structure of MurF from A. baumannii (PDB ID: 4QF5), the studied structures of the mentioned extracts revealed good docking interaction at the active site suggestive of competition with the ATP ligand. These collective findings suggest that extracts of Murraya koenigii (L.) Sprengel seed is a novel prospective for the discovery of drug candidates against infections caused by MDR A. baumannii.

      • Prognostic Value of Prepro-Gastrin Releasing Peptide in Lung Cancer Patients; NCI-Prospective Study

        Shafik, Nevine F,Rahoma, M,Elshimy, Reham AA,El kasem, Fatma M Abou Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.12

        Background: Prior series investigated the expression of prepro-gastrin releasing peptide (prepro-GRP) in the peripheral blood of lung cancer patients. Our aim was to assess any prepro-GRP role as a prognostic factor for small cell lung cancer (SCLC) and NSCLC and correlations with clinical presentation and treatment outcome. Methods: A prospective study was conducted during the time period from the beginning of January 2012 till the end of January 2014. Prepro-GRP expression was analysed using a nested RT-PCR assay in peripheral blood of 62 untreated lung cancer patients attending the National Cancer Institute (NCI), Cairo University, and 30 age and sex matched healthy volunteers. Results: Among the 62 lung cancer cases, there were 24 (38.7%) SCLC, and 38 (61.3%) NSCLC (10 squamous cell carcinomas, 12 adenocarcinomas, 11 large cell carcinomas, 4 undifferentiated carcinomas, and 1 adenosquamous carcinoma). Twenty six patients (41.9%) were prepro-GRP positive. Prepro-GRP expression was higher (58.3%) among SCLC patients compared to NSCLC (squamous cell carcinoma (15.4%), large cell carcinoma (36.4%), and adenocarcinoma (25%)). Mean OS among prepro-GRP negative cases was longer than that among preprogastrin positive cases (17.6 vs 14.9 months). The mean PFS durations among preprogastrin negative versus positive cases were 7.7 vs 4.6 months (p= 0.041). No difference in response to chemotherapy was identified between the groups (p=0.983). Conclusion: Prepro-GRP is suggested to be a useful prognostic marker for lung cancer patients, especially with the fast- growing, bad prognostic SCLC type. More studies should aim at detailed understanding of the mechanisms of prepro-GRP action and its use in monitoring the response to treatment in a larger cohort.

      • Clinical Impact of Overexpression of FOXP3 and WT1 on Disease Outcome in Egyptian Acute Myeloid Leukemia Patients

        Assem, Magda M,Osman, Ahmed,Kandeel, Eman Z,Elshimy, Reham AA,Nassar, Hanan R,Ali, Radwa E Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.10

        Background: In the last decade, it has become clear that change of gene expression may alter the hematopoietic cell quiescent state and consequently play a major role in leukemogenesis. WT1 is known to be a player in acute myeloid leukemia (AML) and FOXP3 has a crucial role in regulating the immune response. Objectives: To evaluate the impact of overexpression of WT1and FOXP3 genes on clinical course in adult and pediatric AML patients in Egypt. Patients and methods: Bone marrow and peripheral blood samples were obtained from 97 de novo non M3 AML patients (63 adult and 34 pediatric). Real-time quantitative PCR was used to detect overexpression WT1 and FOXP3 genes. Patient follow up ranged from 0.2 to 39.0 months with a median of 5 months. Results: In the pediatric group; WT1 was significantly expressed with a high total leukocyte count median 50X109/L (p=0.018). In the adult group, WT1 had an adverse impact on complete remission induction, disease-free survival and overall survival (p=0.02, p=0.035, p=0.019 respectively). FOXP3 overexpression was associated with FAB subtypes AML M0 +M1 vs. M2, M4+M5 (p =0.039) and the presence of hepatomegaly (p=0.005). Conclusions: WT1 and FOXP3 overexpression has an adverse impact on clinical presentation, treatment response and survival of pediatric and adult Egyptian AML patients.

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