45 results on '"Khayat, A."'
Search Results
2. The tale of an endemic shrimp’s exceptional osmoregulation and the ancient Athalassic mangrove oasis
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Giraldes, Bruno W., Boughattas, Sonia, Benslimane, Fatiha M., Althani, Asmaa A., Schubart, Christoph D., Huber, Carla S. R., Utz, Laura R. P., Al-Khayat, Jassim A. A., Sadooni, Fadhil N., and Amado, Enelise M.
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- 2024
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3. Electrophysiological and biochemical effect of zinc oxide nanoparticles on heart functions of male Wistar rats
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Aida Ahmed Hussein, Eman Raafat Moatamed, Mohamed Mahmoud El-desoky, and Zakaria El Khayat
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ZnO NPs ,ZnO bulk form ,Cardiotoxicity ,Electrocardiogram ,Creatine kinase-MB ,Lactate dehydrogenase ,Medicine ,Science - Abstract
Abstract Zinc oxide nanoparticles (ZnO NPs) are one of the most abundantly used nanomaterials in cosmetics and topical products, and nowadays, they are explored in drug delivery and tissue engineering. Some recent data evidenced that they are responsible for cardiotoxic effects and systemic toxicity. The present study aimed to investigate the toxic effect of ZnO NPs (39 nm) on the heart of Wistar rats and to perform a dose–response relationship using three different dose levels (25, 50, 100 mg/kg bw) of ZnO NPs on the electrocardiogram (ECG) readings, the levels of biochemical function parameters of heart, and the oxidative stress and antioxidant biomarkers. Furthermore, zinc concentration level and histopathological examination of heart tissues were determined. ZnO NPs showed a dose-dependent effect, as the 100 mg/kg bw ZnO NPs treated group showed the most significant changes in ECGs parameters: R–R distance, P–R interval, R and T amplitudes, and increased levels of heart enzymes Creatine Kinase- MB (CK-MB) and Lactate dehydrogenase (LDH). On the other hand, elevated zinc concentration levels, oxidative stress biomarkers MDA and NO, and decreased GSH levels were found also in a dose-dependent manner, the results were supported by impairment in the histopathological structure of heart tissues. While the dose of 100 mg/kg bw of ZnO bulk group showed no significant effects on heart function. The present study concluded that ZnO NPs could induce cardiac dysfunctions and pathological lesions mainly in the high dose.
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- 2024
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4. The tale of an endemic shrimp’s exceptional osmoregulation and the ancient Athalassic mangrove oasis
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Bruno W. Giraldes, Sonia Boughattas, Fatiha M. Benslimane, Asmaa A. Althani, Christoph D. Schubart, Carla S. R. Huber, Laura R. P. Utz, Jassim A. A. Al-Khayat, Fadhil N. Sadooni, and Enelise M. Amado
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Medicine ,Science - Abstract
Abstract The hyperarid mangrove in the Middle East is characterised by the absence of rivers or freshwater inputs and is one of the most extreme settings of this ecosystem on Earth. Endemic to Qatar’s hyperarid mangroves, a Palaemon shrimp is uniquely confined to a sole mangrove site in the Arabian Gulf. Within these mangrove channels, we unveiled brine groundwater sources exceeding 70 ppt salinity, contrasting the local marine standard of 42 ppt. Concurrently, a mysid species typically linked to salt pans and groundwater coexists. Stable isotopic analysis implied the existence of a predator–prey dynamic between this mysid species and the studied shrimp. Then, investigating the endemic shrimp’s adaptation to extreme salinity, we conducted osmolarity experiments and phylogenetic studies. Our findings demonstrate that this shrimp transitions from hypo- to hyper-osmoregulation, tolerating salinities from 18 to 68 ppt—an unprecedented osmoregulatory capacity among caridean shrimps. This speciation pattern likely arises from the species osmolarity adaptation, as suggested for other Palaemon congeners. Phylogenetic analysis of the studied Palaemon, along with the mangrove’s geological history, suggests a profound evolutionary interplay between the ecosystem and the shrimp since the Eocene. This study proposes the hyperarid mangrove enclave as an Athalassic mangrove oasis—a distinctive, isolated ecosystem within the desert landscape.
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- 2024
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5. Genetic determinants of severe COVID-19 in young Asian and Middle Eastern patients: a case series
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Beshr Abdulaziz Badla, Mohamed Samer Hanifa, Ruchi Jain, Maha El Naofal, Nour Halabi, Sawsan Yaslam, Sathishkumar Ramaswamy, Alan Taylor, Roudha Alfalasi, Shruti Shenbagam, Hamda Khansaheb, Hanan Al Suwaidi, Norbert Nowotny, Rizwana Popatia, Abdulla Al Khayat, Alawi Alsheikh-Ali, Tom Loney, Laila Mohamed AlDabal, and Ahmad Abou Tayoun
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Medicine ,Science - Abstract
Abstract Studies of genetic factors associated with severe COVID-19 in young adults have been limited in non-Caucasian populations. Here, we clinically characterize a case series of patients with COVID-19, who were otherwise healthy, young adults (N = 55; mean age 34.1 ± SD 5.0 years) from 16 Asian, Middle Eastern, and North African countries. Using whole exome sequencing, we identify rare, likely deleterious variants affecting 16 immune-related genes in 17 out of 55 patients (31%), including 7 patients (41% of all carriers or 12.7% of all patients) who harbored multiple such variants mainly in interferon and toll-like receptor genes. Protein network analysis as well as transcriptomic analysis of nasopharyngeal swabs from an independent COVID-19 cohort (N = 50; 42% Asians and 22% Arabs) revealed that most of the altered genes, as identified by whole exome sequencing, and the associated molecular pathways were significantly altered in COVID-19 patients. Genetic variants tended to be associated with mortality, intensive care admission, and ventilation support. Our clinical cases series, genomic and transcriptomic findings suggest a possible role for interferon pathway genes in severe COVID-19 and highlight the importance of extending genetic studies to diverse populations to better understand the human genetics of disease.
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- 2023
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6. Genetic determinants of severe COVID-19 in young Asian and Middle Eastern patients: a case series
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Badla, Beshr Abdulaziz, Hanifa, Mohamed Samer, Jain, Ruchi, Naofal, Maha El, Halabi, Nour, Yaslam, Sawsan, Ramaswamy, Sathishkumar, Taylor, Alan, Alfalasi, Roudha, Shenbagam, Shruti, Khansaheb, Hamda, Al Suwaidi, Hanan, Nowotny, Norbert, Popatia, Rizwana, Al Khayat, Abdulla, Alsheikh-Ali, Alawi, Loney, Tom, AlDabal, Laila Mohamed, and Abou Tayoun, Ahmad
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- 2023
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7. Variability of blue carbon storage in arid evaporitic environment of two coastal Sabkhas or mudflats
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Al Disi, Zulfa Ali, Naja, Khaled, Rajendran, Sankaran, Elsayed, Hadil, Strakhov, Ivan, Al-Kuwari, Hamad Al Saad, Sadooni, Fadhil, Dittrich, Maria, and Al-Khayat, Jassim Abdulla A.
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- 2023
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8. Variability of blue carbon storage in arid evaporitic environment of two coastal Sabkhas or mudflats
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Zulfa Ali Al Disi, Khaled Naja, Sankaran Rajendran, Hadil Elsayed, Ivan Strakhov, Hamad Al Saad Al-Kuwari, Fadhil Sadooni, Maria Dittrich, and Jassim Abdulla A. Al-Khayat
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Medicine ,Science - Abstract
Abstract Coastal Sabkhas are mudflats found in arid coastal regions that are located within the supratidal zone when high rates of evaporation lead to high salinity. While evaporitic minerals often accumulate underneath the surface, the microbial mats are present on the surface of Sabkhas. Coastal Sabkha, an under-studied ecosystem in Qatar, has the potential to store blue carbon. In the present study, we investigated the carbon storage capacity of two Sabkhas from contrasting geological backgrounds. The spatial and temporal variabilities of the carbon stocks were examined. The results showed that both studied Sabkhas exhibit a considerable potential for soil carbon storage with carbon stocks of 109.11 ± 7.07 Mg C ha−1 and 67.77 ± 18.10 Mg C ha−1 in Dohat Faishakh and Khor al Adaid Sabkha respectively. These values fall within the reported range for carbon stocks in coastal Sabkhas in the region (51–194 Mg C ha−1). Interestingly, the carbon stocks in the sediments of the Sabkhas were higher than those in the sediments of Qatari mangroves (50.17 ± 6.27 Mg C ha−1). These finding suggest that coastal Sabkhas can serve as blue carbon ecosystems in arid environments.
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- 2023
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9. The diminution and modulation role of water-soluble gallic acid-carboxymethyl chitosan conjugates against the induced nephrotoxicity with cisplatin
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Hani S. Hafez, Ebtesam S. Kotb, Zakaria El-Khayat, Reda F. M. Elshaarawy, and Waleed M. Serag
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Medicine ,Science - Abstract
Abstract The toxicity of cisplatin (CDDP) toward the renal tubules and its severe effects on the proximal tubules limits its further use in cancer therapy. The current study was undertaken to evaluate the protective effects of gallic acid-grafted O-carboxymethyl chitosan (GA@CMCS) against nephrotoxicity induced by CDDP in rats. Renal injury was assessed in the GA@CMCS/CDDP-treated rats using kidney injury molecule-1 (KIM-1). Moreover, the levels of reduced glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) were measured. The comet assay was performed to measure the DNA damage. The renoprotective activity of GA@CMCS was supported by histo- and immuno-pathological studies of the kidney. GA@CMCS significantly normalized the increases in kidney homogenate of KIM-1, MDA, and NO-induced by CDDP and significantly increased GSH as compared with the CDDP group. GA@CMCS also significantly protects rat kidneys from CDDP-induced histo- and immuno-pathological changes. Both biochemical findings and histo- and immuno-pathological evidence showed the renoprotective potential of GA@CMCS against CDDP-induced oxidative stress, inflammation, and renal dysfunction in rats. In conclusion, GA@CMCS has been shown to mitigate the nephrotoxicity impact of CDDP in cancer therapy.
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- 2022
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10. Intensification of resveratrol cytotoxicity, pro-apoptosis, oxidant potentials in human colorectal carcinoma HCT-116 cells using zein nanoparticles
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Maan T. Khayat, Mohamed A. Zarka, Dalia Farag. A. El-Telbany, Ali M. El-Halawany, Hussam Ibrahim Kutbi, Walid F. Elkhatib, Ayman M. Noreddin, Ahdab N. Khayyat, Rania Farag A. El-Telbany, Sherif F. Hammad, Ashraf B. Abdel-Naim, Ebtesam M. Alolayan, and Majid Mohammad Al-Sawahli
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Medicine ,Science - Abstract
Abstract Resveratrol (RSV), a non-flavonoid stilbene polyphenol, possesses anti-carcinogenic activities against all the major stages of cancer. Zein nanoparticles (ZN NPs) have been utilized successfully in delivery of variant therapeuticals by virtue of their histocompatible nature. The goal of this work was to comparatively explore the antiproliferative, pro-apoptotic and oxidative stress potentials of RSV-ZN NPs versus RSV against human colorectal carcinoma HCT-116 cells. ZN-RSV NPs were developed and assayed for particle size analysis and RSV diffusion. The selected formula obtained 137.6 ± 8.3 nm as mean particle size, 29.4 ± 1.8 mV zeta potential, 92.3 ± 3.6% encapsulation efficiency. IC50 of the selected formula was significantly lower against HCT-116 cells versus Caco-2 cells. Also, significantly enhanced cellular uptake was generated from RSV-ZN NPs versus free RSV. Enhanced apoptosis was concluded due to increased percentage cells in G2-M and pre-G1 phases. The pro-apoptotic potential was explained by caspase-3 and cleaved caspase-3 increased mRNA expression in addition to NF-κB and miRNA125b decreased expression. Biochemically, ZN-RSV NPs induced oxidative stress as demonstrated by enhanced reactive oxygen species (ROS) generation and endothelial nitric oxide synthase (eNOS) isoenzyme increased levels. Conclusively, ZN-RSV NPs obtained cell cycle inhibition supported with augmented cytotoxicity, uptake and oxidative stress markers levels in HCT-116 tumor cells in comparison with free RSV. These results indicated intensified chemopreventive profile of RSV due to effective delivery utilizing ZN nano-dispersion against colorectal carcinoma HCT-116 cells.
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- 2022
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11. A data completion method for identifying pollution intrusion in aquifers
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Lamia Guellouz and Faten Khayat
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Medicine ,Science - Abstract
Abstract The data completion method combined with the modeling of water flow and solute transport in saturated porous media is used twice to identify the extent of polluted water intrusion from the downstream boundary of an aquifer. The aim of this work is to solve the problem even though data are missing on some of the boundaries, by exploiting the fact that there are over specified data on the other boundaries. Indeed, it is assumed that the flow and the water head are known on the upstream boundary while the pollutant concentrations are known on the downstream boundary. The method developed in this work allows to determine the flows, water heads and pollutant concentrations in the whole domain. The method is applied in different aquifer configurations with pumping wells, the results are satisfactory. The model developed has shown its effectiveness in detecting the intrusion of polluted water and can be used in real cases.
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- 2022
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12. Advances in purification of SARS-CoV-2 spike ectodomain protein using high-throughput screening and non-affinity methods
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Cibelli, Nicole, Arias, Gabriel, Figur, McKenzie, Khayat, Shireen S., Leach, Kristin, Loukinov, Ivan, Shadrick, William, Chuenchor, Watchalee, Tsybovsky, Yaroslav, Gulla, Krishana, and Gowetski, Daniel B.
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- 2022
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13. Intensification of resveratrol cytotoxicity, pro-apoptosis, oxidant potentials in human colorectal carcinoma HCT-116 cells using zein nanoparticles
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Khayat, Maan T., Zarka, Mohamed A., El-Telbany, Dalia Farag. A., El-Halawany, Ali M., Kutbi, Hussam Ibrahim, Elkhatib, Walid F., Noreddin, Ayman M., Khayyat, Ahdab N., El-Telbany, Rania Farag A., Hammad, Sherif F., Abdel-Naim, Ashraf B., Alolayan, Ebtesam M., and Al-Sawahli, Majid Mohammad
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- 2022
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14. A data completion method for identifying pollution intrusion in aquifers
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Guellouz, Lamia and Khayat, Faten
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- 2022
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15. The diminution and modulation role of water-soluble gallic acid-carboxymethyl chitosan conjugates against the induced nephrotoxicity with cisplatin
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Hafez, Hani S., Kotb, Ebtesam S., El-Khayat, Zakaria, Elshaarawy, Reda F. M., and Serag, Waleed M.
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- 2022
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16. Advances in purification of SARS-CoV-2 spike ectodomain protein using high-throughput screening and non-affinity methods
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Nicole Cibelli, Gabriel Arias, McKenzie Figur, Shireen S. Khayat, Kristin Leach, Ivan Loukinov, William Shadrick, Watchalee Chuenchor, Yaroslav Tsybovsky, Vaccine Production Program Analytical Development, Krishana Gulla, and Daniel B. Gowetski
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Medicine ,Science - Abstract
Abstract The spike (S) glycoprotein of the pandemic virus, SARS-CoV-2, is a critically important target of vaccine design and therapeutic development. A high-yield, scalable, cGMP-compliant downstream process for the stabilized, soluble, native-like S protein ectodomain is necessary to meet the extensive material requirements for ongoing research and development. As of June 2021, S proteins have exclusively been purified using difficult-to-scale, low-yield methodologies such as affinity and size-exclusion chromatography. Herein we present the first known non-affinity purification method for two S constructs, S_dF_2P and HexaPro, expressed in the mammalian cell line, CHO-DG44. A high-throughput resin screen on the Tecan Freedom EVO200 automated bioprocess workstation led to identification of ion exchange resins as viable purification steps. The chromatographic unit operations along with industry-standard methodologies for viral clearances, low pH treatment and 20 nm filtration, were assessed for feasibility. The developed process was applied to purify HexaPro from a CHO-DG44 stable pool harvest and yielded the highest yet reported amount of pure S protein. Our results demonstrate that commercially available chromatography resins are suitable for cGMP manufacturing of SARS-CoV-2 Spike protein constructs. We anticipate our results will provide a blueprint for worldwide biopharmaceutical production laboratories, as well as a starting point for process intensification.
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- 2022
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17. Genome-wide association study on blood pressure traits in the Iranian population suggests ZBED9 as a new locus for hypertension
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Goodarz Kolifarhood, Siamak Sabour, Mahdi Akbarzadeh, Bahareh Sedaghati-khayat, Kamran Guity, Saeid Rasekhi Dehkordi, Mahmoud Amiri Roudbar, Farzad Hadaegh, Fereidoun Azizi, and Maryam S. Daneshpour
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Medicine ,Science - Abstract
Abstract High blood pressure is the heritable risk factor for cardiovascular and kidney diseases. Genome-wide association studies(GWAS) on blood pressure traits increase our understanding of its underlying genetic basis. However, a large proportion of GWAS was conducted in Europeans, and some roadblocks deprive other populations to benefit from their results. Iranians population with a high degree of genomic specificity has not been represented in international databases to date, so to fill the gap, we explored the effects of 652,919 genomic variants on Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Hypertension (HTN) in 7694 Iranian adults aged 18 and over from Tehran Cardiometabolic Genetic Study (TCGS). We identified consistent signals on ZBED9 associated with HTN in the genome-wide borderline threshold after adjusting for different sets of environmental predictors. Moreover, strong signals on ABHD17C and suggestive signals on FBN1 were detected for DBP and SBP, respectively, while these signals were not consistent in different GWA analysis. Our finding on ZBED9 was confirmed for all BP traits by linkage analysis in an independent sample. We found significant associations with similar direction of effects and allele frequency of genetic variants on ZBED9 with DBP (genome-wide threshold) and HTN (nominal threshold) in GWAS summary data of UK Biobank. Although there is no strong evidence to support the function of ZBED9 in blood pressure regulation, it provides new insight into the pleiotropic effects of hypertension and other cardiovascular diseases.
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- 2021
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18. Programming of intestinal homeostasis in male rat offspring after maternal exposure to chlorpyrifos and/or to a high fat diet
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Marion Guibourdenche, Hiba El Khayat El Sabbouri, Narimane Djekkoun, Hafida Khorsi-Cauet, Véronique Bach, Pauline M. Anton, and Jérôme Gay-Quéheillard
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Medicine ,Science - Abstract
Abstract Alteration of programming of the intestinal wall maturation may be responsible for non-communicable chronic diseases in adulthood. It may originate from prenatal exposure of mothers to deleterious environmental factors such as pesticides or western diet. This work was undertaken to determine whether disturbances of the digestive tract function and of innate immunity of offspring at adulthood could be due to maternal exposure to a pesticide, chlorpyrifos (CPF) and a High Fat Diet (HFD) starting 4 months before gestation and lasting until weaning of offspring. Fifty-one male Wistar rats coming from 4 groups of dams exposed to CPF, HFD, both and control were followed from birth to 8 weeks of age. They were fed standard chow and received no treatment. The maternal pesticide exposure slows down fetal and postnatal weight gain without histological injuries of the gut mucosa. CPF or HFD both induced modifications of tight junctions and mucins genes expressions without inducing an increase in epithelial permeability or an inflammatory state. Co-exposure to both CPF and HFD did not exacerbate the effects observed with each factor separately. Despite the lack of direct contact except through breast milk until weaning, CPF or HFD maternal exposure have demonstrated preliminary gut barrier impacts on offspring.
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- 2021
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19. Kernel machine SNP set analysis finds the association of BUD13, ZPR1, and APOA5 variants with metabolic syndrome in Tehran Cardio-metabolic Genetics Study
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Sajedeh Masjoudi, Bahareh Sedaghati-khayat, Niloufar Javanrouh Givi, Leila Najd Hassan Bonab, Fereidoun Azizi, and Maryam S. Daneshpour
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Medicine ,Science - Abstract
Abstract Metabolic syndrome (MetS) is one of the most important risk factors for cardiovascular disease. The 11p23.3 chromosomal region plays a potential role in the pathogenesis of MetS. The present study aimed to assess the association between 18 single nucleotide polymorphisms (SNPs) located at the BUD13, ZPR1, and APOA5 genes with MetS in the Tehran Cardio-metabolic Genetics Study (TCGS). In 5421 MetS affected and non-affected participants, we analyzed the data using two models. The first model (MetS model) examined SNPs' association with MetS. The second model (HTg-MetS Model) examined the association of SNPs with MetS affection participants who had a high plasma triglyceride (TG). The four-gamete rules were used to make SNP sets from correlated nearby SNPs. The kernel machine regression models and single SNP regression evaluated the association between SNP sets and MetS. The kernel machine results showed two sets over three sets of correlated SNPs have a significant joint effect on both models (p
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- 2021
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20. A small interfering RNA (siRNA) database for SARS-CoV-2
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Inácio Gomes Medeiros, André Salim Khayat, Beatriz Stransky, Sidney Santos, Paulo Assumpção, and Jorge Estefano Santana de Souza
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Medicine ,Science - Abstract
Abstract Coronavirus disease 2019 (COVID-19) rapidly transformed into a global pandemic, for which a demand for developing antivirals capable of targeting the SARS-CoV-2 RNA genome and blocking the activity of its genes has emerged. In this work, we presented a database of SARS-CoV-2 targets for small interference RNA (siRNA) based approaches, aiming to speed the design process by providing a broad set of possible targets and siRNA sequences. The siRNAs sequences are characterized and evaluated by more than 170 features, including thermodynamic information, base context, target genes and alignment information of sequences against the human genome, and diverse SARS-CoV-2 strains, to assess possible bindings to off-target sequences. This dataset is available as a set of four tables, available in a spreadsheet and CSV (Comma-Separated Values) formats, each one corresponding to sequences of 18, 19, 20, and 21 nucleotides length, aiming to meet the diversity of technology and expertise among laboratories around the world. A metadata table (Supplementary Table S1), which describes each feature, is also provided in the aforementioned formats. We hope that this database helps to speed up the development of new target antivirals for SARS-CoV-2, contributing to a possible strategy for a faster and effective response to the COVID-19 pandemic.
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- 2021
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21. GWAS findings improved genomic prediction accuracy of lipid profile traits: Tehran Cardiometabolic Genetic Study
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Mahdi Akbarzadeh, Saeid Rasekhi Dehkordi, Mahmoud Amiri Roudbar, Mehdi Sargolzaei, Kamran Guity, Bahareh Sedaghati-khayat, Parisa Riahi, Fereidoun Azizi, and Maryam S. Daneshpour
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Medicine ,Science - Abstract
Abstract In recent decades, ongoing GWAS findings discovered novel therapeutic modifications such as whole-genome risk prediction in particular. Here, we proposed a method based on integrating the traditional genomic best linear unbiased prediction (gBLUP) approach with GWAS information to boost genetic prediction accuracy and gene-based heritability estimation. This study was conducted in the framework of the Tehran Cardio-metabolic Genetic study (TCGS) containing 14,827 individuals and 649,932 SNP markers. Five SNP subsets were selected based on GWAS results: top 1%, 5%, 10%, 50% significant SNPs, and reported associated SNPs in previous studies. Furthermore, we randomly selected subsets as large as every five subsets. Prediction accuracy has been investigated on lipid profile traits with a tenfold and 10-repeat cross-validation algorithm by the gBLUP method. Our results revealed that genetic prediction based on selected subsets of SNPs obtained from the dataset outperformed the subsets from previously reported SNPs. Selected SNPs’ subsets acquired a more precise prediction than whole SNPs and much higher than randomly selected SNPs. Also, common SNPs with the most captured prediction accuracy in the selected sets caught the highest gene-based heritability. However, it is better to be mindful of the fact that a small number of SNPs obtained from GWAS results could capture a highly notable proportion of variance and prediction accuracy.
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- 2021
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22. SARS-CoV-2 infection susceptibility influenced by ACE2 genetic polymorphisms: insights from Tehran Cardio-Metabolic Genetic Study
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Hossein Lanjanian, Maryam Moazzam-Jazi, Mehdi Hedayati, Mahdi Akbarzadeh, Kamran Guity, Bahareh Sedaghati-khayat, Fereidoun Azizi, and Maryam S. Daneshpour
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Medicine ,Science - Abstract
Abstract The genetic variations among individuals are one of the notable factors determining disease severity and drug response. Nowadays, COVID-19 pandemic has been adversely affecting many aspects of human life. We used the Tehran Cardio-Metabolic Genetic Study (TCGS) data that is an ongoing genetic study including the whole-genome sequencing of 1200 individuals and chip genotyping of more than 15,000 participants. Here, the effect of ACE2 variations by focusing on the receptor-binding site of SARS-CoV-2 and ACE2 cleavage by TMPRSS2 protease were investigated through simulations study. After analyzing TCGS data, 570 genetic variations on the ACE2 gene, including single nucleotide polymorphisms (SNP) and insertion/deletion (INDEL) were detected. Interestingly, two observed missense variants, K26R and S331F, which only the first one was previously reported, can reduce the receptor affinity for the viral Spike protein. Moreover, our bioinformatics simulation of 3D structures and docking of proteins explains important details of ACE2-Spike and ACE2-TMPRSS2 interactions, especially the critical role of Arg652 of ACE2 for protease function of TMPRSS2 was uncovered. As our results show that the genetic variation of ACE2 can at least influence the affinity of this receptor to its partners, we need to consider the genetic variations on ACE2 as well as other genes in the pathways that contribute to the pathogenesis of COVID-19 for designing efficient drugs and vaccines.
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- 2021
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23. Genome-wide association study on blood pressure traits in the Iranian population suggests ZBED9 as a new locus for hypertension
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Kolifarhood, Goodarz, Sabour, Siamak, Akbarzadeh, Mahdi, Sedaghati-khayat, Bahareh, Guity, Kamran, Rasekhi Dehkordi, Saeid, Amiri Roudbar, Mahmoud, Hadaegh, Farzad, Azizi, Fereidoun, and Daneshpour, Maryam S.
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- 2021
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24. Programming of intestinal homeostasis in male rat offspring after maternal exposure to chlorpyrifos and/or to a high fat diet
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Guibourdenche, Marion, El Khayat El Sabbouri, Hiba, Djekkoun, Narimane, Khorsi-Cauet, Hafida, Bach, Véronique, Anton, Pauline M., and Gay-Quéheillard, Jérôme
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- 2021
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25. A small interfering RNA (siRNA) database for SARS-CoV-2
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Medeiros, Inácio Gomes, Khayat, André Salim, Stransky, Beatriz, Santos, Sidney, Assumpção, Paulo, and de Souza, Jorge Estefano Santana
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- 2021
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26. Kernel machine SNP set analysis finds the association of BUD13, ZPR1, and APOA5 variants with metabolic syndrome in Tehran Cardio-metabolic Genetics Study
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Masjoudi, Sajedeh, Sedaghati-khayat, Bahareh, Givi, Niloufar Javanrouh, Bonab, Leila Najd Hassan, Azizi, Fereidoun, and Daneshpour, Maryam S.
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- 2021
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27. GWAS findings improved genomic prediction accuracy of lipid profile traits: Tehran Cardiometabolic Genetic Study
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Akbarzadeh, Mahdi, Dehkordi, Saeid Rasekhi, Roudbar, Mahmoud Amiri, Sargolzaei, Mehdi, Guity, Kamran, Sedaghati-khayat, Bahareh, Riahi, Parisa, Azizi, Fereidoun, and Daneshpour, Maryam S.
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- 2021
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28. SARS-CoV-2 infection susceptibility influenced by ACE2 genetic polymorphisms: insights from Tehran Cardio-Metabolic Genetic Study
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Lanjanian, Hossein, Moazzam-Jazi, Maryam, Hedayati, Mehdi, Akbarzadeh, Mahdi, Guity, Kamran, Sedaghati-khayat, Bahareh, Azizi, Fereidoun, and Daneshpour, Maryam S.
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- 2021
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29. Targeting aurora kinases as a potential prognostic and therapeutical biomarkers in pediatric acute lymphoblastic leukaemia
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Moreira-Nunes, Caroline Aquino, Mesquita, Felipe Pantoja, Portilho, Adrhyann Jullyanne de Sousa, Mello Júnior, Fernando Augusto Rodrigues, Maués, Jersey Heitor da Silva, Pantoja, Laudreísa da Costa, Wanderley, Alayde Vieira, Khayat, André Salim, Zuercher, William J., Montenegro, Raquel Carvalho, de Moraes-Filho, Manoel Odorico, and de Moraes, Maria Elisabete Amaral
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- 2020
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30. Cryo-electron microscopy structure of the 70S ribosome from Enterococcus faecalis
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Murphy, Eileen L., Singh, Kavindra V., Avila, Bryant, Kleffmann, Torsten, Gregory, Steven T., Murray, Barbara E., Krause, Kurt L., Khayat, Reza, and Jogl, Gerwald
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- 2020
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31. Characterization of pharmacogenetic markers related to Acute Lymphoblastic Leukemia toxicity in Amazonian native Americans population
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de Carvalho, Darlen Cardoso, Wanderley, Alayde Vieira, dos Santos, André Mauricio Ribeiro, Moreira, Fabiano Cordeiro, de Sá, Roberta Borges Andrade, Fernandes, Marianne Rodrigues, Modesto, Antonio André Conde, de Souza, Tatiane Piedade, Cohen-Paes, Amanda, Leitão, Luciana Pereira Colares, Rodrigues, Juliana Carla Gomes, da Silva, Artur Luiz da Costa, Guerreiro, João Farias, Santos, Sidney, Khayat, André Salim, de Assumpção, Paulo Pimentel, and dos Santos, Ney Pereira Carneiro
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- 2020
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32. Molecular characterization of sarcomatoid clear cell renal cell carcinoma unveils new candidate oncogenic drivers
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Malouf, Gabriel G., Flippot, Ronan, Dong, Yiyu, Dinatale, Renzo G., Chen, Ying-Bei, Su, Xiaoping, Compérat, Eva, Rouprêt, Morgan, Mano, Roy, Blum, Kyle A., Yao, Hui, Mouawad, Roger, Spano, Jean-Philippe, Khayat, David, Karam, Jose A., Ho, Thai H., Tickoo, Satish K., Russo, Paul, Hsieh, James J., Tannir, Nizar M., and Hakimi, Abraham A.
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- 2020
- Full Text
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33. Expression of long non-coding RNA MFI2-AS1 is a strong predictor of recurrence in sporadic localized clear-cell renal cell carcinoma
- Author
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Ronan Flippot, Roger Mouawad, Jean-Philippe Spano, Morgan Rouprêt, Eva Compérat, Marc-Olivier Bitker, Jérôme Parra, Christophe Vaessen, Frederick Allanic, Quentin Manach, Nizar M. Tannir, David Khayat, Xiaoping Su, and Gabriel G. Malouf
- Subjects
Medicine ,Science - Abstract
Abstract Prediction of recurrence is a challenge for the development of adjuvant treatments in clear-cell renal cell carcinoma (ccRCC). In these tumors, expression of long non-coding RNAs (lncRNAs) are deregulated and closely associated with prognosis. Thus, we aimed to predict ccRCC recurrence risk using lncRNA expression. We identified prognostic lncRNAs in a training set of 351 localized ccRCCs from The Cancer Genome Atlas and validated lncRNA-based recurrence classification in an independent cohort of 167 localized ccRCCs. We identified lncRNA MFI2-AS1 as best candidate in the training set. In the validation cohort, MFI2-AS1 expression was independently associated with shorter disease-free survival (Hazard Ratio (HR) for relapse 3.5, p = 0.0001). Combined with Leibovich classification, MFI2-AS1 status improved prediction of recurrence (C-index 0.70) compared to MFI2-AS1 alone (0.67) and Leibovich classification alone (0.66). In patients with aggressive tumors (Leibovich ≥5), MFI2-AS1 expression was associated with dramatically increased risk of relapse (HR 12.16, p
- Published
- 2017
- Full Text
- View/download PDF
34. Genome-wide association study on blood pressure traits in the Iranian population suggests ZBED9 as a new locus for hypertension
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Mahmoud Amiri Roudbar, Fereidoun Azizi, Siamak Sabour, Bahareh Sedaghati-khayat, Kamran Guity, Goodarz Kolifarhood, Mahdi Akbarzadeh, Farzad Hadaegh, Saeid Rasekhi Dehkordi, and Maryam S. Daneshpour
- Subjects
0301 basic medicine ,Adult ,Male ,Science ,Population ,Diastole ,Locus (genetics) ,Genome-wide association study ,Blood Pressure ,030204 cardiovascular system & hematology ,Biology ,Arrhythmias ,Iran ,Article ,03 medical and health sciences ,0302 clinical medicine ,Quantitative Trait, Heritable ,Genetic linkage ,Chronic kidney disease ,Humans ,Genetic Predisposition to Disease ,cardiovascular diseases ,education ,Allele frequency ,Genetic association ,Genetics ,education.field_of_study ,Multidisciplinary ,Middle Aged ,030104 developmental biology ,Blood pressure ,Cardiovascular diseases ,Hypertension ,Medicine ,Female ,Genome-Wide Association Study - Abstract
High blood pressure is the heritable risk factor for cardiovascular and kidney diseases. Genome-wide association studies(GWAS) on blood pressure traits increase our understanding of its underlying genetic basis. However, a large proportion of GWAS was conducted in Europeans, and some roadblocks deprive other populations to benefit from their results. Iranians population with a high degree of genomic specificity has not been represented in international databases to date, so to fill the gap, we explored the effects of 652,919 genomic variants on Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Hypertension (HTN) in 7694 Iranian adults aged 18 and over from Tehran Cardiometabolic Genetic Study (TCGS). We identified consistent signals on ZBED9 associated with HTN in the genome-wide borderline threshold after adjusting for different sets of environmental predictors. Moreover, strong signals on ABHD17C and suggestive signals on FBN1 were detected for DBP and SBP, respectively, while these signals were not consistent in different GWA analysis. Our finding on ZBED9 was confirmed for all BP traits by linkage analysis in an independent sample. We found significant associations with similar direction of effects and allele frequency of genetic variants on ZBED9 with DBP (genome-wide threshold) and HTN (nominal threshold) in GWAS summary data of UK Biobank. Although there is no strong evidence to support the function of ZBED9 in blood pressure regulation, it provides new insight into the pleiotropic effects of hypertension and other cardiovascular diseases.
- Published
- 2021
35. Kernel machine SNP set analysis finds the association of BUD13, ZPR1, and APOA5 variants with metabolic syndrome in Tehran Cardio-metabolic Genetics Study
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Maryam S. Daneshpour, Niloufar Javanrouh Givi, Sajedeh Masjoudi, Fereidoun Azizi, Bahareh Sedaghati-khayat, and Leila Najd Hassan Bonab
- Subjects
Male ,Science ,Single-nucleotide polymorphism ,Disease ,Biology ,Iran ,Polymorphism, Single Nucleotide ,Article ,Machine Learning ,medicine ,Genetics ,SNP ,Humans ,Genetic Predisposition to Disease ,Allele ,Metabolic Syndrome ,Multidisciplinary ,Molecular medicine ,Cardiometabolic Risk Factors ,Membrane Transport Proteins ,RNA-Binding Proteins ,Regression analysis ,Odds ratio ,medicine.disease ,Apolipoprotein A-V ,Chromosomal region ,Medicine ,Female ,Metabolic syndrome - Abstract
Metabolic syndrome (MetS) is one of the most important risk factors for cardiovascular disease. The 11p23.3 chromosomal region plays a potential role in the pathogenesis of MetS. The present study aimed to assess the association between 18 single nucleotide polymorphisms (SNPs) located at the BUD13, ZPR1, and APOA5 genes with MetS in the Tehran Cardio-metabolic Genetics Study (TCGS). In 5421 MetS affected and non-affected participants, we analyzed the data using two models. The first model (MetS model) examined SNPs' association with MetS. The second model (HTg-MetS Model) examined the association of SNPs with MetS affection participants who had a high plasma triglyceride (TG). The four-gamete rules were used to make SNP sets from correlated nearby SNPs. The kernel machine regression models and single SNP regression evaluated the association between SNP sets and MetS. The kernel machine results showed two sets over three sets of correlated SNPs have a significant joint effect on both models (p –7; HTg-MetS: OR = 1.4, p = 2.3 × 10–11) and the T allele in rs651821 (MetS: OR = 1.3, p = 2.8 × 10–7; HTg-MetS: OR = 1.4, p = 3.6 × 10–11). In the present study, the kernel machine regression models could help assess the association between the BUD13, ZPR1, and APOA5 gene variants (11p23.3 region) with lipid-related traits in MetS and MetS affected with high TG.
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- 2021
36. GWAS findings improved genomic prediction accuracy of lipid profile traits: Tehran Cardiometabolic Genetic Study
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Fereidoun Azizi, Kamran Guity, Saeid Rasekhi Dehkordi, Mahmoud Amiri Roudbar, Maryam S. Daneshpour, Mehdi Sargolzaei, Mahdi Akbarzadeh, Parisa Riahi, and Bahareh Sedaghati-khayat
- Subjects
Science ,Inheritance Patterns ,Genome-wide association study ,Single-nucleotide polymorphism ,Computational biology ,Biology ,Best linear unbiased prediction ,Significant snps ,Iran ,Article ,Metabolic Diseases ,Snp markers ,Developmental biology ,medicine ,Genetics ,SNP ,Humans ,Multidisciplinary ,medicine.diagnostic_test ,Molecular Sequence Annotation ,Genomics ,Heritability ,Lipids ,Computational biology and bioinformatics ,Phenotype ,Cardiovascular Diseases ,Medicine ,Lipid profile ,Genome-Wide Association Study - Abstract
In recent decades, ongoing GWAS findings discovered novel therapeutic modifications such as whole-genome risk prediction in particular. Here, we proposed a method based on integrating the traditional genomic best linear unbiased prediction (gBLUP) approach with GWAS information to boost genetic prediction accuracy and gene-based heritability estimation. This study was conducted in the framework of the Tehran Cardio-metabolic Genetic study (TCGS) containing 14,827 individuals and 649,932 SNP markers. Five SNP subsets were selected based on GWAS results: top 1%, 5%, 10%, 50% significant SNPs, and reported associated SNPs in previous studies. Furthermore, we randomly selected subsets as large as every five subsets. Prediction accuracy has been investigated on lipid profile traits with a tenfold and 10-repeat cross-validation algorithm by the gBLUP method. Our results revealed that genetic prediction based on selected subsets of SNPs obtained from the dataset outperformed the subsets from previously reported SNPs. Selected SNPs’ subsets acquired a more precise prediction than whole SNPs and much higher than randomly selected SNPs. Also, common SNPs with the most captured prediction accuracy in the selected sets caught the highest gene-based heritability. However, it is better to be mindful of the fact that a small number of SNPs obtained from GWAS results could capture a highly notable proportion of variance and prediction accuracy.
- Published
- 2021
37. Cryo-electron microscopy structure of the 70S ribosome from Enterococcus faecalis
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Reza Khayat, Bryant Avila, Barbara E. Murray, Eileen L Murphy, Gerwald Jogl, Kurt L. Krause, Steven T. Gregory, Torsten Kleffmann, and Kavindra V. Singh
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0301 basic medicine ,Translation ,Protein Conformation ,lcsh:Medicine ,medicine.disease_cause ,Ribosome ,Enterococcus faecalis ,Article ,03 medical and health sciences ,0302 clinical medicine ,Protein structure ,Large ribosomal subunit ,medicine ,Escherichia coli ,Electron microscopy ,lcsh:Science ,Multidisciplinary ,Binding Sites ,biology ,Chemistry ,Cryoelectron Microscopy ,lcsh:R ,Ribosomal RNA ,biology.organism_classification ,Anti-Bacterial Agents ,030104 developmental biology ,Biochemistry ,Ribosome Subunits ,Transfer RNA ,lcsh:Q ,Ribosome Subunits, Large ,Structural biology ,030217 neurology & neurosurgery - Abstract
Enterococcus faecalis is a gram-positive organism responsible for serious infections in humans, but as with many bacterial pathogens, resistance has rendered a number of commonly used antibiotics ineffective. Here, we report the cryo-EM structure of the E. faecalis 70S ribosome to a global resolution of 2.8 Å. Structural differences are clustered in peripheral and solvent exposed regions when compared with Escherichia coli, whereas functional centres, including antibiotic binding sites, are similar to other bacterial ribosomes. Comparison of intersubunit conformations among five classes obtained after three-dimensional classification identifies several rotated states. Large ribosomal subunit protein bL31, which forms intersubunit bridges to the small ribosomal subunit, assumes different conformations in the five classes, revealing how contacts to the small subunit are maintained throughout intersubunit rotation. A tRNA observed in one of the five classes is positioned in a chimeric pe/E position in a rotated ribosomal state. The 70S ribosome structure of E. faecalis now extends our knowledge of bacterial ribosome structures and may serve as a basis for the development of novel antibiotic compounds effective against this pathogen.
- Published
- 2020
38. Targeting aurora kinases as a potential prognostic and therapeutical biomarkers in pediatric acute lymphoblastic leukaemia
- Author
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Felipe Pantoja Mesquita, Fernando Augusto Rodrigues Mello Júnior, William J. Zuercher, Alayde Vieira Wanderley, Jersey Heitor da Silva Maués, Maria Elisabete Amaral de Moraes, Raquel Carvalho Montenegro, André Salim Khayat, Laudreísa da Costa Pantoja, Adrhyann Jullyanne de Sousa Portilho, Manoel Odorico de Moraes-Filho, and Caroline Aquino Moreira-Nunes
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0301 basic medicine ,Male ,Programmed cell death ,Cell biology ,Cell cycle checkpoint ,Molecular biology ,Fusion Proteins, bcr-abl ,Article ,03 medical and health sciences ,0302 clinical medicine ,Gene expression ,medicine ,Genetics ,Biomarkers, Tumor ,Aurora Kinase B ,Humans ,Protein Interaction Maps ,Child ,Mitosis ,Gene ,Cancer genetics ,Cancer ,Aurora Kinase A ,Haematological cancer ,Multidisciplinary ,Kinase ,business.industry ,Infant ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,Leukemia ,030104 developmental biology ,Apoptosis ,030220 oncology & carcinogenesis ,Case-Control Studies ,Child, Preschool ,Cancer research ,Female ,business ,K562 Cells ,Brazil - Abstract
Aurora kinases (AURKA and AURKB) are mitotic kinases with an important role in the regulation of several mitotic events, and in hematological malignancies, AURKA and AURKB hyperexpression are found in patients with cytogenetic abnormalities presenting a unfavorable prognosis. The aim of this study was evaluated the mRNA expression profile of pediatric Acute Lymphoblastic Leukaemia (ALL) patients and the efficacy of two AURKA and AURKB designed inhibitors (GW809897X and GW806742X) in a leukemia cell line as a potential novel therapy for ALL patients. Cellular experiments demonstrated that both inhibitors induced cell death with caspase activation and cell cycle arrest, however only the GW806742X inhibitor decreased with more efficacy AURKA and AURKB expression in K-562 leukemia cells. In ALL patients both AURKA and AURKB showed a significant overexpression, when compared to health controls. Moreover, AURKB expression level was significant higher than AURKA in patients, and predicted a poorer prognosis with significantly lower survival rates. No differences were found in AURKA and AURKB expression between gene fusions, immunophenotypic groups, white blood cells count, gender or age. In summary, the results in this study indicates that the AURKA and AURKB overexpression are important findings in pediatric ALL, and designed inhibitor, GW806742X tested in vitro were able to effectively inhibit the gene expression of both aurora kinases and induce apoptosis in K-562 cells, however our data clearly shown that AURKB proves to be a singular finding and potential prognostic biomarker that may be used as a promising therapeutic target to those patients.
- Published
- 2020
39. SARS-CoV-2 infection susceptibility influenced by ACE2 genetic polymorphisms: insights from Tehran Cardio-Metabolic Genetic Study
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Lanjanian, Hossein, Moazzam-Jazi, Maryam, Hedayati, Mehdi, Akbarzadeh, Mahdi, Guity, Kamran, Sedaghati-khayat, Bahareh, Azizi, Fereidoun, and Daneshpour, Maryam S.
- Subjects
Genotype ,Science ,Mutation, Missense ,Gene Expression ,Single-nucleotide polymorphism ,Iran ,medicine.disease_cause ,Polymorphism, Single Nucleotide ,Article ,INDEL Mutation ,Genetic variation ,medicine ,Humans ,Indel ,Gene ,Genotyping ,Whole genome sequencing ,Genetics ,Mutation ,Multidisciplinary ,Binding Sites ,Whole Genome Sequencing ,SARS-CoV-2 ,Serine Endopeptidases ,COVID-19 ,Personalized medicine ,Protein Structure, Tertiary ,Molecular Docking Simulation ,Spike Glycoprotein, Coronavirus ,Medicine ,Angiotensin-Converting Enzyme 2 ,Disease Susceptibility ,Molecular modelling ,hormones, hormone substitutes, and hormone antagonists ,Protein Binding - Abstract
The genetic variations among individuals are one of the notable factors determining disease severity and drug response. Nowadays, COVID-19 pandemic has been adversely affecting many aspects of human life. We used the Tehran Cardio-Metabolic Genetic Study (TCGS) data that is an ongoing genetic study including the whole-genome sequencing of 1200 individuals and chip genotyping of more than 15,000 participants. Here, the effect of ACE2 variations by focusing on the receptor-binding site of SARS-CoV-2 and ACE2 cleavage by TMPRSS2 protease were investigated through simulations study. After analyzing TCGS data, 570 genetic variations on the ACE2 gene, including single nucleotide polymorphisms (SNP) and insertion/deletion (INDEL) were detected. Interestingly, two observed missense variants, K26R and S331F, which only the first one was previously reported, can reduce the receptor affinity for the viral Spike protein. Moreover, our bioinformatics simulation of 3D structures and docking of proteins explains important details of ACE2-Spike and ACE2-TMPRSS2 interactions, especially the critical role of Arg652 of ACE2 for protease function of TMPRSS2 was uncovered. As our results show that the genetic variation of ACE2 can at least influence the affinity of this receptor to its partners, we need to consider the genetic variations on ACE2 as well as other genes in the pathways that contribute to the pathogenesis of COVID-19 for designing efficient drugs and vaccines.
- Published
- 2020
40. Characterization of pharmacogenetic markers related to Acute Lymphoblastic Leukemia toxicity in Amazonian native Americans population
- Author
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Alayde Vieira Wanderley, Juliana Carla Gomes Rodrigues, Artur Silva, João Farias Guerreiro, Luciana Pereira Colares Leitão, Paulo Pimentel Assumpção, Amanda Cohen-Paes, Darlen Cardoso de Carvalho, Tatiane Piedade de Souza, André Salim Khayat, André Mauricio Ribeiro dos Santos, Marianne Rodrigues Fernandes, Antônio André Conde Modesto, Ney Pereira Carneiro dos Santos, Sidney Santos, Roberta Borges Andrade de Sá, and Fabiano Cordeiro Moreira
- Subjects
0301 basic medicine ,False discovery rate ,Genetic Markers ,Male ,Pharmacogenomic Variants ,Molecular biology ,Population ,Ethnic group ,lcsh:Medicine ,Antineoplastic Agents ,Biology ,Indigenous ,Article ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,Humans ,education ,lcsh:Science ,Child ,Cancer ,education.field_of_study ,Multidisciplinary ,Indians, South American ,lcsh:R ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Genotype frequency ,Exact test ,030104 developmental biology ,Evolutionary biology ,030220 oncology & carcinogenesis ,Child, Preschool ,lcsh:Q ,Female ,Pharmacogenetics ,Brazil - Abstract
Acute Lymphoblastic Leukemia (ALL) is the most common cancer in children. Differences are found among ethnic groups in the results of the treatment of pediatric ALL. In general, children with a high level of native American ancestry tend to respond less positively to ALL treatments, which may be related to specific genomic variants found in native American groups. Despite the evidence, few data are available on the distribution of the pharmacogenomic variants relevant to the treatment of ALL in traditional Amerindian populations, such the those of the Amazon region. Given this, the present study investigated 27 molecular markers related to the treatment of ALL in Amerindians from Brazilian Amazonia and compared the frequencies with those recorded previously on five continents, that are available in the 1,000 Genomes database. The variation in the genotype frequencies among populations was evaluated using Fisher’s exact test. The False Discovery Rate method was used to correct the results of the multiple analyses. Significant differences were found in the frequencies of the majority of markers between the Amerindian populations and those of other regions around the world. These findings highlight the unique genetic profile of the indigenous population of Brazilian Amazonia, which may reflect a distinct therapeutic profile for the treatment of ALL in these populations.
- Published
- 2020
41. Molecular characterization of sarcomatoid clear cell renal cell carcinoma unveils new candidate oncogenic drivers
- Author
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Nizar M. Tannir, Yiyu Dong, Ronan Flippot, Xiaoping Su, Morgan Rouprêt, Jose A. Karam, Paul Russo, Eva Compérat, Gabriel G. Malouf, James J. Hsieh, Satish K. Tickoo, Ying-Bei Chen, Renzo G. DiNatale, Hui Yao, A. Ari Hakimi, Roger Mouawad, Jean Philippe Spano, Roy Mano, Kyle A. Blum, David Khayat, Thai H. Ho, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Strasbourg, Institut de Cancérologie de Strasbourg Europe (ICANS), Memorial Sloan Kettering Cancer Center (MSKCC), The University of Texas M.D. Anderson Cancer Center [Houston], CHU Tenon [AP-HP], Sorbonne Université (SU), Epidémiologie, Systèmes d'Information, Modélisation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), MD Anderson Cancer Center [Houston], The University of Texas Health Science Center at Houston (UTHealth), Mayo Clinic [Scottsdale], Mayo Clinic, Mayo Clinic [Rochester], Washington University in Saint Louis (WUSTL), and univOAK, Archive ouverte
- Subjects
Male ,Cell ,Gene regulatory network ,lcsh:Medicine ,Mice ,0302 clinical medicine ,Gene Regulatory Networks ,lcsh:Science ,Cancer genetics ,Cancer ,Laser capture microdissection ,YAP1 ,Neurofibromin 2 ,0303 health sciences ,Multidisciplinary ,Kidney Neoplasms ,Up-Regulation ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Signal Transduction ,animal structures ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Laser Capture Microdissection ,Protein Serine-Threonine Kinases ,Biology ,Article ,03 medical and health sciences ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,medicine ,Carcinoma ,Animals ,Humans ,Genetic Predisposition to Disease ,Hippo Signaling Pathway ,Carcinoma, Renal Cell ,Adaptor Proteins, Signal Transducing ,Cell Proliferation ,030304 developmental biology ,Cell Nucleus ,Hippo signaling pathway ,Cell growth ,lcsh:R ,YAP-Signaling Proteins ,Sequence Analysis, DNA ,medicine.disease ,Clear cell renal cell carcinoma ,Transcriptional Coactivator with PDZ-Binding Motif Proteins ,Mutation ,Trans-Activators ,Cancer research ,lcsh:Q ,Neoplasm Transplantation ,Transcription Factors - Abstract
Sarcomatoid clear-cell renal cell carcinomas (sRCC) are associated with dismal prognosis. Genomic alterations associated with sarcomatoid dedifferentiation are poorly characterized. We sought to define the genomic landscape of sRCC and uncover potentially actionable therapeutic targets. We assessed the genomic landscape of sRCC using targeted panel sequencing including patients with microdissected sarcomatoid and epithelial components. Along with common genomic alterations associated with clear-cell histology, we found that Hippo was one of the most frequently altered pathways in these tumours. Hippo alterations were differentially enriched in sRCC compared to non-sRCC. Functional analysis showed that Hippo members mutations were associated with higher nuclear accumulation of YAP/TAZ, core effectors of the Hippo pathway. In a NF2-mutant sRCC model, YAP1 knockdown and NF2 reconstitution suppressed cell proliferation, tumour growth and invasion, both in vitro and in vivo. Overall, we show that Hippo pathway alterations are a feature of sRCC, and enable the exploration of the Hippo pathway as a novel potential therapeutic target.
- Published
- 2020
42. Expression of long non-coding RNA MFI2-AS1 is a strong predictor of recurrence in sporadic localized clear-cell renal cell carcinoma
- Author
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Quentin Manach, Roger Mouawad, Christophe Vaessen, Marc Olivier Bitker, Eva Comperat, Jean Philippe Spano, Nizar M. Tannir, Xiaoping Su, Gabriel G. Malouf, Jérôme Parra, David Khayat, Ronan Flippot, Frederick Allanic, Morgan Rouprêt, HAL UPMC, Gestionnaire, Institut Universitaire de Cancérologie [Paris] (IUC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service d'Oncologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pathologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), The University of Texas M.D. Anderson Cancer Center [Houston], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Universitaire de Cancérologie [Sorbonne Université] (IUC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and CHU Tenon [AP-HP]
- Subjects
0301 basic medicine ,Oncology ,Male ,Kaplan-Meier Estimate ,Bioinformatics ,[SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology ,Cohort Studies ,0302 clinical medicine ,Renal cell carcinoma ,Regulation of gene expression ,Aged, 80 and over ,0303 health sciences ,Multidisciplinary ,Hazard ratio ,Hematology ,Middle Aged ,Prognosis ,Kidney Neoplasms ,Long non-coding RNA ,3. Good health ,Gene Expression Regulation, Neoplastic ,030220 oncology & carcinogenesis ,Cohort ,[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,Medicine ,Female ,RNA, Long Noncoding ,Adult ,medicine.medical_specialty ,Science ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Article ,03 medical and health sciences ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Internal medicine ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,Carcinoma ,Biomarkers, Tumor ,medicine ,Humans ,Carcinoma, Renal Cell ,Aged ,030304 developmental biology ,business.industry ,Gene Expression Profiling ,medicine.disease ,[SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology ,Gene expression profiling ,Clear cell renal cell carcinoma ,030104 developmental biology ,Cancer research ,Neoplasm Recurrence, Local ,business - Abstract
Prediction of recurrence is a challenge for the development of adjuvant treatments in clear-cell renal cell carcinoma (ccRCC). In these tumors, expression of long non-coding RNAs (lncRNAs) are deregulated and closely associated with prognosis. Thus, we aimed to predict ccRCC recurrence risk using lncRNA expression. We identified prognostic lncRNAs in a training set of 351 localized ccRCCs from The Cancer Genome Atlas and validated lncRNA-based recurrence classification in an independent cohort of 167 localized ccRCCs. We identified lncRNA MFI2-AS1 as best candidate in the training set. In the validation cohort, MFI2-AS1 expression was independently associated with shorter disease-free survival (Hazard Ratio (HR) for relapse 3.5, p = 0.0001). Combined with Leibovich classification, MFI2-AS1 status improved prediction of recurrence (C-index 0.70) compared to MFI2-AS1 alone (0.67) and Leibovich classification alone (0.66). In patients with aggressive tumors (Leibovich ≥5), MFI2-AS1 expression was associated with dramatically increased risk of relapse (HR 12.16, p MFI2-AS1 who had favorable outcomes. Compared to normal samples, MFI2-AS1 was upregulated in tumor tissue, and higher expression was associated with metastatic dissemination. Overall, MFI2-AS1 status improves patient stratification in localized ccRCC, which supports further integration of lncRNAs in molecular cancer classifications.
- Published
- 2017
43. The interaction of fat mass and obesity associated gene polymorphisms and dietary fiber intake in relation to obesity phenotypes
- Author
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Hosseini-Esfahani, Firoozeh, primary, Koochakpoor, Gelareh, additional, Daneshpour, Maryam S., additional, Mirmiran, Parvin, additional, Sedaghati-khayat, Bahareh, additional, and Azizi, Fereidoun, additional
- Published
- 2017
- Full Text
- View/download PDF
44. Expression of long non-coding RNA MFI2-AS1 is a strong predictor of recurrence in sporadic localized clear-cell renal cell carcinoma
- Author
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Flippot, Ronan, primary, Mouawad, Roger, additional, Spano, Jean-Philippe, additional, Rouprêt, Morgan, additional, Compérat, Eva, additional, Bitker, Marc-Olivier, additional, Parra, Jérôme, additional, Vaessen, Christophe, additional, Allanic, Frederick, additional, Manach, Quentin, additional, Tannir, Nizar M., additional, Khayat, David, additional, Su, Xiaoping, additional, and Malouf, Gabriel G., additional
- Published
- 2017
- Full Text
- View/download PDF
45. Unique Transcriptomic Profile of Collecting Duct Carcinomas Relative to Upper Tract Urothelial Carcinomas and other Kidney Carcinomas
- Author
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Malouf, Gabriel G., primary, Compérat, Eva, additional, Yao, Hui, additional, Mouawad, Roger, additional, Lindner, Veronique, additional, Rioux-leclercq, Nathalie, additional, Verkarre, Virginie, additional, Leroy, Xavier, additional, Dainese, Linda, additional, Classe, Marion, additional, Descotes, Jean-Luc, additional, Barthelemy, Philippe, additional, Yacoub, Mokrane, additional, Rouprêt, Morgan, additional, Bernhard, Jean-Christophe, additional, Creighton, Chad J., additional, Spano, Jean-Philippe, additional, Su, Xiaoping, additional, and Khayat, David, additional
- Published
- 2016
- Full Text
- View/download PDF
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