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11.
12.
The Protein Journal - As expected, several new variants of Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) emerged and have been detected around the world throughout this Coronavirus... 相似文献
13.
Parthenolide sensitizes cells to X-ray-induced cell killing through inhibition of NF-kappaB and split-dose repair 总被引:2,自引:0,他引:2
Mendonca MS Chin-Sinex H Gomez-Millan J Datzman N Hardacre M Comerford K Nakshatri H Nye M Benjamin L Mehta S Patino F Sweeney C 《Radiation research》2007,168(6):689-697
Human cancers have multiple alterations in cell signaling pathways that promote resistance to cytotoxic therapy such as X rays. Parthenolide is a sesquiterpene lactone that has been shown to inhibit several pro-survival cell signaling pathways, induce apoptosis, and enhance chemotherapy-induced cell killing. We investigated whether parthenolide would enhance X-ray-induced cell killing in radiation resistant, NF-kappaB-activated CGL1 cells. Treatment with 5 microM parthenolide for 48 to 72 h inhibited constitutive NF-kappaB binding and cell growth, reduced plating efficiency, and induced apoptosis through stabilization of p53 (TP53), induction of the pro-apoptosis protein BAX, and phosphorylation of BID. Parthenolide also enhanced radiation-induced cell killing, increasing the X-ray sensitivity of CGL1 cells by a dose modification factor of 1.6. Flow cytometry revealed that parthenolide reduced the percentage of X-ray-resistant S-phase cells due to induction of p21 waf1/cip1 (CDKN1A) and the onset of G1/S and G2/M blocks, but depletion of radioresistant S-phase cells does not explain the observed X-ray sensitization. Further studies demonstrated that the enhancement of X-ray-induced cell killing by parthenolide is due to inhibition of split-dose repair. 相似文献
14.
Shehnaz Fatima 《Journal of receptor and signal transduction research》2013,33(3):243-252
AbstractSimultaneous inhibition of EGFR and HER2 by dual-targeting inhibitors is an established anti-cancer strategy. Therefore, a recent trend in drug discovery involves understanding the features of such dual inhibitors. In this study, three different G-QSAR models were developed corresponding to individual EGFR, HER2 and the dual-model for both receptors. The dual-model provided site-specific information wherein (i) increasing electronegative character and higher index of saturated carbon at R4 position; (ii) presence of chlorine atom at R2 position; (iii) decreasing alpha modified shape index at R1 and R3 positions; and (iv) less electronegativity at R2 position; were found important for enhancing the dual activity. Also, comparison of dual-model with the EGFR/HER2 individual models revealed that it incorporates the properties of both models and, thus, represents a combination of EGFR/HER2. Further, fragment analysis revealed that R2 and R4 are important for imparting high potency while specificity is decided by R1/R3 fragment. We also checked the predictive ability of the dual-model by determining applicability domain using William’s plot. Also, analysis of active molecules showed they show favorable substitutions that agree with the constructed dual-model. Thus, we have been successful in developing a single dual-response QSAR model to get an insight into various structural features influencing EGFR/HER2 activity. 相似文献
15.
Population density in cetaceans can be estimated through photo-identification, mark-recapture, land-based observations and visual estimative. We the aim to contribute with conservation strategies, we used line transects (distance method) to estimate the population density of the river dolphin, S. guianensis, in the estuarine region of Cananéia, Southeastern Brazil. The study, developed from May 2003 until April 2004, during dry and rainy seasons and different times of the day, included a sampling area divided into three sectors according to their proximity to the open sea: Sector I (the closest to the open sea); Sector II (with a large flow of fresh water and a salient declivity); and Sector III (with a large flow of fresh water and non salient declivity). Onboard random sampling was carried out in all three sectors, and dolphins seen from the bow to 90 degrees on both port and starboard sides, were registered along with their position and distance from the boat. The total density found was 12.41 ind/km2 (CV = 25.53%) with an average of 2.2 individuals per group for both periods of the day, morning and afternoon. Densities also varied between dry and rainy seasons, being lower in the first with 5.77 ind/km2 (CV = 27.87%) than in the second 20.28 ind/km2 (CV = 31.95%), respectively. Regarding the three sectors, a non-causal heterogeneous distribution was found: Sector I was the most populated (D = 33.10 ind/km2, CV = 13.34%), followed by Sector II (D = 7.8 ind/km2, CV = 21.07%) and Sector III (D = 3.04 ind/km2, CV = 34.04%). The aforementioned area, due to its proximity to the open sea, has the highest salinity level and therefore has the greatest chance of holding most of the marine fish schools which can be cornered by dolphins on high declivity areas during fishing activities. This suggests that food availability may be the most important factor on the river dolphin's distribution in the estuary. Similar studies will contribute to a better understanding of these populations and are essential for future conservation strategies. 相似文献
16.
Geoffrey S. Gottlieb Robert A. Smith Ndeye Mery Dia Badiane Selly Ba Stephen E. Hawes Macoumba Toure Alison K. Starling Fatou Traore Fatima Sall Stephen L. Cherne Joshua Stern Kim G. Wong Paul Lu Moon Kim Dana N. Raugi Airin Lam James I. Mullins Nancy B. Kiviat Papa Salif Sow for the UW-Dakar HIV- Study Group 《PloS one》2011,6(7)
Background
Antiretroviral therapy for HIV-2 infection is hampered by intrinsic resistance to many of the drugs used to treat HIV-1. Limited studies suggest that the integrase inhibitors (INIs) raltegravir and elvitegravir have potent activity against HIV-2 in culture and in infected patients. There is a paucity of data on genotypic variation in HIV-2 integrase that might confer intrinsic or transmitted INI resistance.Methods
We PCR amplified and analyzed 122 HIV-2 integrase consensus sequences from 39 HIV-2–infected, INI-naive adults in Senegal, West Africa. We assessed genetic variation and canonical mutations known to confer INI-resistance in HIV-1.Results
No amino acid-altering mutations were detected at sites known to be pivotal for INI resistance in HIV-1 (integrase positions 143, 148 and 155). Polymorphisms at several other HIV-1 INI resistance-associated sites were detected at positions 72, 95, 125, 154, 165, 201, 203, and 263 of the HIV-2 integrase protein.Conclusion
Emerging genotypic and phenotypic data suggest that HIV-2 is susceptible to the new class of HIV integrase inhibitors. We hypothesize that intrinsic HIV-2 integrase variation at “secondary” HIV-1 INI-resistance sites may affect the genetic barrier to HIV-2 INI resistance. Further studies will be needed to assess INI efficacy as part of combination antiretroviral therapy in HIV-2–infected patients. 相似文献17.
18.
Md Iqbal Kabir Md Bayzidur Rahman Wayne Smith Mirza Afreen Fatima Lusha Abul Hasnat Milton 《PloS one》2015,10(8)
Background
Bangladesh is one of the most vulnerable countries to climate change. People are getting educated at different levels on how to deal with potential impacts. One such educational mode was the preparation of a school manual, for high school students on climate change and health protection endorsed by the National Curriculum and Textbook Board, which is based on a 2008 World Health Organization manual. The objective of this study was to test the effectiveness of the manual in increasing the knowledge level of the school children about climate change and health adaptation.Methods
This cluster randomized intervention trial involved 60 schools throughout Bangladesh, with 3293 secondary school students participating. School upazilas (sub-districts) were randomised into intervention and control groups, and two schools from each upazila were randomly selected. All year seven students from both groups of schools sat for a pre-test of 30 short questions of binary response. A total of 1515 students from 30 intervention schools received the intervention through classroom training based on the school manual and 1778 students of the 30 control schools did not get the manual but a leaflet on climate change and health issues. Six months later, a post-intervention test of the same questionnaire used in the pre-test was performed at both intervention and control schools. The pre and post test scores were analysed along with the demographic data by using random effects model.Results
None of the various school level and student level variables were significantly different between the control and intervention group. However, the intervention group had a 17.42% (95% CI: 14.45 to 20.38, P = <0.001) higher score in the post-test after adjusting for pre-test score and other covariates in a multi-level linear regression model.Conclusions
These results suggest that school-based intervention for climate change and health adaptation is effective for increasing the knowledge level of school children on this topic. 相似文献19.
Nida Fatima Kolachi Tasneem Gul Kazi Hassan Imran Afridi Naveed Kazi Ghulam Abbas Kandhro Abdul Qadir Shah Jameel Ahmed Baig Sham Kumar Wadhwa Sumaira Khan Faheem Shah Mohammad Khan Jamali Mohammad Balal Arain 《Biological trace element research》2011,143(1):116-130
The aim of the present study was to compare the level of copper (Cu), iron (Fe) and zinc (Zn) in biological samples (serum, blood, urine, and scalp hair) of patients suffering from different viral hepatitis (A, B, C, D, and E; n?=?521) of both gender age ranged 31–45 years. For comparative study, 255 age-matched control subjects, of both genders residing in the same city were selected as referents. The elements in the biological samples were analyzed by flame atomic absorption spectrophotometry, prior to microwave-assisted acid digestion. The validity and accuracy of the methodology was checked by using certified reference materials (CRMs) and with those values obtained by conventional wet acid digestion method on same CRMs. The results of this study showed that the mean values of Cu and Fe were higher in blood, sera, and scalp hair samples of hepatitis patients, while Zn level was found to be lower than age-matched control subjects. The urinary levels of these elements were found to be higher in the hepatitis patients than in the age-matched healthy controls (p?<?0.05). These results are consistent with literature-reported data, confirming that the deficiency of zinc and hepatic iron and copper overload can directly cause lipid peroxidation and eventually hepatic damage. 相似文献
20.
Nasereddine Hamadi Ahmed Mansour Memy H. Hassan Fatima Khalifi‐Touhami Osama Badary 《Journal of biochemical and molecular toxicology》2012,26(10):384-392
The objective of this study was to investigate the ameliorative property and potential mechanism of resveratrol (RVT) in a dose of 10 mg/kg for 15 consecutive days against liver injury in streptozotocin‐induced diabetic rats. Diabetic rats significantly (P < 0.05) exhibited liver injury manifested by increased aspartylaminotransferase, alanine aminotransferase, and bilirubin; disturbed liver weight to body weight; and confirmed by hematoxylin and eosin staining. Liver from diabetic rats exhibited significant increase in malondialdehyde level and significant decrease in reduced glutathione, glutathione‐S‐transferase, quinone reductase, catalase, and superoxide dismutase. Diabetic rats showed significant disturbance in serum lipid profile. Treatment with RVT significantly (P < 0.05) abrogated diabetes‐induced perturbation in these parameters and liver histology. These data suggest that RVT treatment is associated with promising hepatoprotective effect against diabetes‐induced liver damage via reduction of serum glucose level and oxidative damage and improving serum lipid profile. © 2012 Wiley Periodicals, Inc. J Biochem Mol Toxicol 26:384–392, 2012; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21432 相似文献