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Ahmed Kamal D. Dastagiri M. Janaki Ramaiah E. Vijaya Bharathi J. Surendranadha Reddy G. Balakishan Pranjal Sarma S.N.C.V.L. Pushpavalli Manika Pal-Bhadra Aarti Juvekar Subrata Sen Surekha Zingde 《Bioorganic & medicinal chemistry》2010,18(18):6666-6677
A series of 2,5-diaryloxadiazole linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates have been prepared and evaluated for their anticancer activity. These conjugates have shown promising activity with GI50 values ranging from <0.1 to 0.29 μΜ. It is observed that some of these conjugates particularly 4a, 4d, 4i and 4l exhibit significant anticancer activity. Some detailed biological assays relating to the cell cycle aspects associated to Bax and caspases have been examined with a view to understand the mechanism of action of these conjugates. 相似文献
64.
Tarek Kamal Motawi Olfat Gamil Shaker Shohda Assem El-Maraghy Mahmoud Ahmed Senousy 《PloS one》2015,10(3)
MicroRNAs are messengers during interferon-virus interplay and are involved in antiviral immunity, however, little is known about interferon-related microRNAs regarding their detection in serum and their potential use as non-invasive diagnostic and prognostic biomarkers in chronic hepatitis C (CHC). To elucidate some of the molecular aspects underlying failure of pegylated interferon-α/ribavirin therapy, we investigated pretreatment expression profiles of seven selected interferon-related microRNAs (miR-146a, miR-34a, miR-130a, miR-19a, miR-192, miR-195, and miR-296) by quantitative RT-PCR custom array technology in serum of Egyptian CHC genotype 4 patients and whether their pretreatment levels would predict patient response to the combination therapy. One hundred and six CHC patients and forty matched healthy controls were included. Patients were divided into sustained virological response (SVR) and non-responder (NR) groups. Serum miR-34a, miR-130a, miR-19a, miR-192, miR-195, and miR-296 were upregulated, whereas serum miR-146a was downregulated in CHC compared to controls. Significant correlations were found between expression levels of studied microRNAs and also with clinical data. Pretreatment levels of miR-34a, miR-130a, and miR-195 were significantly higher, whereas miR-192 and miR-296 levels were significantly lower in SVR than NR patients. miR-19a and miR-146a levels were not significantly different between the two groups. miR-34a was superior to differentiate CHC from controls, whereas miR-296 was superior to discriminate SVR from NR patients by receiver operating characteristic analysis. Multivariate logistic analysis revealed miR-34a and miR-195 as independent predictors for SVR and miR-192 as an independent variable for non-response. In conclusion, pretreatment expression profiles of five interferon-related microRNAs are associated with treatment outcome in CHC. Of these, miR-34a, miR-195, and miR-192 could predict treatment response. The profiling results could be used as novel non-invasive diagnostic and prognostic pharmacogenetic biomarkers for treatment personalization in CHC and could help to identify new microRNA-based antivirals. 相似文献
65.
Rachel D. Starks Andreas M. Beyer Deng Fu Guo Lauren Boland Qihong Zhang Val C. Sheffield Kamal Rahmouni 《PLoS genetics》2015,11(6)
Insulin and its receptor are critical for the regulation of metabolic functions, but the mechanisms underlying insulin receptor (IR) trafficking to the plasma membrane are not well understood. Here, we show that Bardet Biedl Syndrome (BBS) proteins are necessary for IR localization to the cell surface. We demonstrate that the IR interacts physically with BBS proteins, and reducing the expression of BBS proteins perturbs IR expression in the cell surface. We show the consequence of disrupting BBS proteins for whole body insulin action and glucose metabolism using mice lacking different BBS genes. These findings demonstrate the importance of BBS proteins in underlying IR cell surface expression. Our data identify defects in trafficking and localization of the IR as a novel mechanism accounting for the insulin resistance commonly associated with human BBS. This is supported by the reduced surface expression of the IR in fibroblasts derived from patients bearing the M390R mutation in the BBS1 gene. 相似文献
66.
Hosein Dalili Firouzeh Nili Mahdi Sheikh Amir Kamal Hardani Mamak Shariat Fatemeh Nayeri 《PloS one》2015,10(3)
Objectives
To compare the Conventional, Specified, Expanded and Combined Apgar scoring systems in predicting birth asphyxia and the adverse early neurologic outcomes.Methods
This prospective cohort study was conducted on 464 admitted neonates. In the delivery room, after delivery the umbilical cord was double clamped and a blood samples was obtained from the umbilical artery for blood gas analysis, meanwhile on the 1- , 5- and 10- minutes Conventional, Specified, Expanded, and Combined Apgar scores were recorded. Then the neonates were followed and intracranial ultrasound imaging was performed, and the following information were recorded: the occurrence of birth asphyxia, hypoxic Ischemic Encephalopathy (HIE), intraventricular hemorrhage (IVH), and neonatal seizure.Results
The Combined-Apgar score had the highest sensitivity (97%) and specificity (99%) in predicting birth asphyxia, followed by the Specified-Apgar score that was also highly sensitive (95%) and specific (97%). The Expanded-Apgar score was highly specific (95%) but not sensitive (67%) and the Conventional-Apgar score had the lowest sensitivity (81%) and low specificity (81%) in predicting birth asphyxia. When adjusted for gestational age, only the low 5-minute Combined-Apgar score was independently associated with the occurrence of HIE (B = 1.61, P = 0.02) and IVH (B = 2.8, P = 0.01).Conclusions
The newly proposed Combined-Apgar score is highly sensitive and specific in predicting birth asphyxia and also is a good predictor of the occurrence of HIE and IVH in asphyxiated neonates. 相似文献67.
Reshu Saxena Sudipti Gupta Kavita Singh Kalyan Mitra Anil Kumar Tripathi Raj Kamal Tripathi 《PloS one》2015,10(4)
Nef is an accessory viral protein that promotes HIV-1 replication, facilitating alterations in cellular pathways via multiple protein-protein interactions. The advent of proteomics has expanded the focus on better identification of novel molecular pathways regulating disease progression. In this study, nef was sequenced from randomly selected patients, however, sequence variability identified did not elicited any specific mutation that could have segregated HIV-1 patients in different stages of disease progression. To explore the difference in Nef functionality based on sequence variability we used proteomics approach. Proteomic profiling was done to compare the effect of Nef variants in host cell protein expression. 2DGE in control and Nef transfected SupT1 cells demonstrated several differentially expressed proteins. Fourteen protein spots were detected with more than 1.5 fold difference. Significant down regulation was seen in six unique protein spots in the Nef treated cells. Proteins were identified as Cyclophilin A, EIF5A-1 isoform B, Rho GDI 1 isoform a, VDAC1, OTUB1 and α-enolase isoform 1 (ENO1) through LC-MS/MS. The differential expression of the 6 proteins was analyzed by Real time PCR, Western blotting and Immunofluorescence studies with two Nef variants (RP14 and RP01) in SupT1 cells. There was contrasting difference between the effect of these Nef variants upon the expression of these six proteins. Downregulation of α-enolase (ENO1), VDAC1 and OTUB1 was more significant by Nef RP01 whereas Cyclophilin A and RhoGDI were found to be more downregulated by Nef RP14. This difference in Nef variants upon host protein expression was also studied through a site directed mutant of Nef RP01 (55AAAAAAA61) and the effect was found to be reversed. Deciphering the role of these proteins mediated by Nef variants will open a new avenue of research in understanding Nef mediated pathogenesis. Overall study determines modulation of cellular protein expression in T cells by HIV-1 Nef variants. 相似文献
68.
Sarder Tanzir Hossain Petros Isaakidis Karuna D. Sagili Shayla Islam Md Akramul Islam Hemant Deepak Shewade S. M. Mostofa Kamal Ashaque Husain 《PloS one》2015,10(6)
Objectives
To determine, in areas supported by BRAC, Bangladesh i) the pre-diagnosis and pre-treatment attrition among presumptive and confirmed Multi-Drug Resistant Tuberculosis (MDR-TB) patients and ii) factors associated with attrition.Methods
This was a retrospective cohort study involving record review. Presumptive MDR-TB patients from peripheral microscopy centres serving 60% of the total population of Bangladesh were included in the study. Attrition and turnaround time for MDR-TB diagnosis by Xpert MTB/RIF and treatment initiation were calculated between July 2012 and June 2014.Results
Of 836 presumptive MDR-TB patients referred from 398 peripheral microscopy centres, 161 MDR-TB patients were diagnosed. The number of diagnosed MDR-TB patients was less than country estimates of MDR-TB patients (2000 cases) during the study period. Among those referred, pre-diagnosis and pre-treatment attrition was 17% and 21% respectively. Median turnaround time for MDR-TB testing, result receipt and treatment initiation was four, zero and five days respectively. Farmers (RR=2.3, p=0.01) and daily wage laborers (RR=2.1, p=0.04) had twice the risk of having pre-diagnosis attrition. Poor record-keeping and unreliable upkeep of presumptive MDR-TB patient databases were identified as challenges at the peripheral microscopy centres.Conclusion
There was a low proportion of pre-diagnosis and pre-treatment attrition in patients with presumptive and confirmed MDR-TB under programmatic conditions. However, the recording and reporting system did not detect all presumptive MDR-TB patients, highlighting the need to improve the system in order to prevent morbidity, mortality and transmission of MDR-TB in the community. 相似文献69.
70.
Andrea Vivian Alvarez-Oxiley Noelita Melo de Sousa Jean-Luc Hornick Kamal Touati Gysbert C van der Weijden Marcel AM Taverne Otto Szenci Jean-François Beckers 《Acta veterinaria Scandinavica》2010,52(1):9