Publications by authors named "Ashraf Khalil"

109 Publications

Early assessment of lung function in coronavirus patients using invariant markers from chest X-rays images.

Sci Rep 2021 06 8;11(1):12095. Epub 2021 Jun 8.

BioImaging Laboratory, Department of Bioengineering, University of Louisville, Louisville, KY, USA.

The primary goal of this manuscript is to develop a computer assisted diagnostic (CAD) system to assess pulmonary function and risk of mortality in patients with coronavirus disease 2019 (COVID-19). The CAD system processes chest X-ray data and provides accurate, objective imaging markers to assist in the determination of patients with a higher risk of death and thus are more likely to require mechanical ventilation and/or more intensive clinical care.To obtain an accurate stochastic model that has the ability to detect the severity of lung infection, we develop a second-order Markov-Gibbs random field (MGRF) invariant under rigid transformation (translation or rotation of the image) as well as scale (i.e., pixel size). The parameters of the MGRF model are learned automatically, given a training set of X-ray images with affected lung regions labeled. An X-ray input to the system undergoes pre-processing to correct for non-uniformity of illumination and to delimit the boundary of the lung, using either a fully-automated segmentation routine or manual delineation provided by the radiologist, prior to the diagnosis. The steps of the proposed methodology are: (i) estimate the Gibbs energy at several different radii to describe the inhomogeneity in lung infection; (ii) compute the cumulative distribution function (CDF) as a new representation to describe the local inhomogeneity in the infected region of lung; and (iii) input the CDFs to a new neural network-based fusion system to determine whether the severity of lung infection is low or high. This approach is tested on 200 clinical X-rays from 200 COVID-19 positive patients, 100 of whom died and 100 who recovered using multiple training/testing processes including leave-one-subject-out (LOSO), tenfold, fourfold, and twofold cross-validation tests. The Gibbs energy for lung pathology was estimated at three concentric rings of increasing radii. The accuracy and Dice similarity coefficient (DSC) of the system steadily improved as the radius increased. The overall CAD system combined the estimated Gibbs energy information from all radii and achieved a sensitivity, specificity, accuracy, and DSC of 100%, 97% ± 3%, 98% ± 2%, and 98% ± 2%, respectively, by twofold cross validation. Alternative classification algorithms, including support vector machine, random forest, naive Bayes classifier, K-nearest neighbors, and decision trees all produced inferior results compared to the proposed neural network used in this CAD system. The experiments demonstrate the feasibility of the proposed system as a novel tool to objectively assess disease severity and predict mortality in COVID-19 patients. The proposed tool can assist physicians to determine which patients might require more intensive clinical care, such a mechanical respiratory support.
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http://dx.doi.org/10.1038/s41598-021-91305-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187631PMC
June 2021

A comprehensive review summarizing the recent biomedical applications of functionalized carbon nanofibers.

J Biomed Mater Res B Appl Biomater 2021 Mar 21. Epub 2021 Mar 21.

Materials Science and Technology Program, College of Arts and Sciences, Qatar University, Doha, 2713, Qatar.

Since the discovery and fabrication of carbon nanofibers (CNFs) over a decade ago, scientists foster to discover novel myriad potential applications for this material in both biomedicine and industry. The unique economic viability, mechanical, electrical, optical, thermal, and structural properties of CNFs led to their rapid emergence. CNFs become an artificial intelligence platform for different uses, including a wide range of biomedical applications. Furthermore, CNFs have exceptionally large surface areas that make them flexible for tailoring and functionalization on demand. This review highlights the recent progress and achievements of CNFs in a wide range of biomedical fields, including cancer therapy, biosensing, tissue engineering, and wound dressing. Besides the synthetic techniques of CNFs, their potential toxicity and limitations, as biomaterials in real clinical settings, will be presented. This review discusses CNF's future investigations in other biomedical fields, including gene delivery and bioimaging and CNFs risk assessment.
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http://dx.doi.org/10.1002/jbm.b.34828DOI Listing
March 2021

Mesoporous silica coated carbon nanofibers reduce embryotoxicity via ERK and JNK pathways.

Mater Sci Eng C Mater Biol Appl 2021 Mar 27;122:111910. Epub 2021 Jan 27.

Biomedical Research Centre, Qatar University, PO Box 2713, Doha, Qatar; College of Medicine, QU Health, Qatar University, PO Box 2713, Doha, Qatar. Electronic address:

Carbon nanofibers (CNFs) have been implicated in biomedical applications, yet, they are still considered as a potential hazard. Conversely, mesoporous silica is a biocompatible compound that has been used in various biomedical applications. In this regard, we recently reported that CNFs induce significant toxicity on the early stage of embryogenesis in addition to the inhibition of its angiogenesis. Thus, we herein use mesoporous silica coating of CNFs (MCNFs) in order to explore their outcome on normal development and angiogenesis using avian embryos at 3 days and its chorioallantoic membrane (CAM) at 6 days of incubation. Our data show that mesoporous silica coating of CNFs significantly reduces embryotoxicity provoked by CNFs. However, MCNFs exhibit slight increase in angiogenesis inhibition in comparison with CNFs. Further investigation revealed that MCNFs slightly deregulate the expression patterns of key controller genes involved in cell proliferation, survival, angiogenesis, and apoptosis as compared to CNFs. We confirmed these data using avian primary normal embryonic fibroblast cells established in our lab. Regarding the molecular pathways, we found that MCNFs downregulate the expression of ERK1/ERK2, p-ERK1/ERK2 and JNK1/JNK2/JNK3, thus indicating a protective role of MCNFs via ERK and JNK pathways. Our data suggest that coating CNFs with a layer of mesoporous silica can overcome their toxicity making them suitable for use in biomedical applications. Nevertheless, further investigations are required to evaluate the effects of MCNFs and their mechanisms using different in vitro and in vivo models.
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http://dx.doi.org/10.1016/j.msec.2021.111910DOI Listing
March 2021

Evaluating Flinders Technology Associates card for transporting bacterial isolates and retrieval of bacterial DNA after various storage conditions.

Vet World 2020 Oct 28;13(10):2243-2251. Epub 2020 Oct 28.

Institute of Biotechnology and Genetic Engineering, City of Scientific Research and Technology Applications, Borg Elarab, Alexandria, Egypt.

Background And Aim: Flinders Technology Associates (FTA) cards simplify sample storage, transport, and extraction by reducing cost and time for diagnosis. This study evaluated the FTA suitability for safe transport and storage of Gram-positive and Gram-negative bacterial cells of animal origin on its liquid culture form and from organ impression smears (tissues) under the same routine condition of microbiological laboratory along with detecting their nucleic acid over different storage conditions.

Materials And Methods: Increase in bacterial count from 10 to 10 (colony-forming units/mL) of 78 isolates representing seven bacterial species was applied onto cards. FTA cards were grouped and inoculated by these bacteria and then stored at different conditions of 24-27°C, 4°C, and -20°C for 24 h, for 2 weeks, for 1 and 3 month storage, respectively. Bacteriological examination was done, after which bacterial DNA was identified using specific primers for each bacterial type and detected by polymerase chain reaction (PCR).

Results: The total percentage of recovered bacteria from FTA cards was 66.7% at 24-27°C for 24 h, the detection limit was 100% in Gram-positive species, while it was 57.4% in Gram-negative ones. Regarding viable cell detection from organ impression smears, it was successful under the previous conditions. No live bacterial cells were observed by bacteriological isolation rather than only at 24-27°C for 24 h storage. All bacterial DNA were sufficiently confirmed by the PCR technique at different conditions.

Conclusion: Overall, the FTA card method was observed to be a valid tool for nucleic acid purification for bacteria of animal origin in the form of culture or organ smears regardless of its Gram type and is used for a short time only 24 h for storage and transport of live bacteria specifically Gram-positive type. Moreover, the bacterial nucleic acid was intact after storage in -20°C for 3 months and was PCR amplifiable.
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http://dx.doi.org/10.14202/vetworld.2020.2243-2251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704315PMC
October 2020

A comprehensive review on the antiviral activities of chalcones.

J Drug Target 2021 04 16;29(4):403-419. Epub 2020 Dec 16.

College of Pharmacy, QU Health, Qatar University, Doha, Qatar.

Some viral outbreaks have plagued the world since antiquity, including the most recent COVID-19 pandemic. The continuous spread and emergence of new viral diseases have urged the discovery of novel treatment options that can overcome the limitations of currently marketed antiviral drugs. Chalcones are natural open chain flavonoids that are found in various plants and can be synthesised in labs. Several studies have shown that these small organic molecules exert a number of pharmacological activities, including antiviral, anti-inflammatory, antimicrobial and anticancer. The purpose of this review is to provide a summary of the antiviral activities of chalcones and their derivatives on a set of human viral infections and their potential for targeting the most recent COVID-19 disease. Accordingly, we herein review chalcones activities on the following human viruses: Middle East respiratory syndrome coronavirus, severe acute respiratory syndrome coronavirus, human immunodeficiency, influenza, human rhinovirus, herpes simplex, dengue, human cytomegalovirus, hepatitis B and C, Rift Valley fever and Venezuelan equine encephalitis. We hope that this review will pave the way for the design and development of potentially potent and broad-spectrum chalcone based antiviral drugs.
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http://dx.doi.org/10.1080/1061186X.2020.1853759DOI Listing
April 2021

Significant Toxic Effect of Carbon Nanofibers at the Early Stage of Embryogenesis.

J Biomed Nanotechnol 2020 Jun;16(6):975-984

Implementation of carbon nanofibers (CNFs) in biomedical applications have successful outcomes, however, they are still considered as a potential hazard. We herein used avian embryos at 3 days and its chorioallantoic membrane (CAM) at 6 days of incubation to evaluate the impact of synthesized CNFs on the early stage of embryogenesis and angiogenesis. Our data point out that 50 g/embryo concentration of CNFs provoke adverse effects as 75% of CNFs-exposed embryos die within 1-5 days after exposure compared with their matched controls. Furthermore, CNFs significantly inhibit angiogenesis of the CAM after 48-hours post-treatment. Additionally, RT-PCR analysis on seven key controller genes responsible for proliferation, survival, angiogenesis, and apoptosis showed that these genes are deregulated in brain, heart, and liver tissues of CNFs-exposed embryos compared to their matched control. Our investigation suggests that CNFs could have a toxic effect on the early stages of embryogenesis as well as angiogenesis. Nevertheless, further investigations are required to evaluate the effects of CNFs and elucidate their mechanism on the early stage of the normal development and human health.
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http://dx.doi.org/10.1166/jbn.2020.2937DOI Listing
June 2020

Water-Pipe Smoking Exposure Deregulates a Set of Genes Associated with Human Head and Neck Cancer Development and Prognosis.

Toxics 2020 Sep 18;8(3). Epub 2020 Sep 18.

College of Medicine, QU Health, Qatar University, Doha PO Box 2713, Qatar.

Water-pipe smoking (WPS) is becoming the most popular form of tobacco use among the youth, especially in the Middle East, replacing cigarettes rapidly and becoming a major risk of tobacco addiction worldwide. Smoke from WPS contains similar toxins as those present in cigarette smoke and is linked directly with different types of cancers including lung and head and neck (HN) carcinomas. However, the underlying molecular pathways and/or target genes responsible for the carcinogenic process are still unknown. In this study, human normal oral epithelial (HNOE) cells, NanoString PanCancer Pathways panel of 770 gene transcripts and quantitative real-time polymerase chain reaction (qRT-PCR) analysis were applied to discover differentially expressed genes (DEG) modulated by WPS. In silico analysis was performed to analyze the impact of these genes in HN cancer patient's biology and outcome. We found that WPS can induce the epithelial-mesenchymal transition (EMT: hallmark of cancer progression) of HNOE cells. More significantly, our analysis of NanoString revealed 23 genes deregulated under the effect of WPS, responsible for the modulation of cell cycle, proliferation, migration/invasion, apoptosis, signal transduction, and inflammatory response. Further analysis was performed using qRT-PCR of HNOE WPS-exposed and unexposed cells supported the reliability of our NanoString data. Moreover, we demonstrate those DEG to be upregulated in cancer compared with normal tissue. Using the Kaplan-Meier analysis, we observed a significant association between WPS-deregulated genes and relapse-free survival/overall survival in HN cancer patients. Our findings imply that WPS can modulate EMT as well as a set of genes that are directly involved in human HN carcinogenesis, thereby affecting HN cancer patients' survival.
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http://dx.doi.org/10.3390/toxics8030073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560251PMC
September 2020

The implication of genetic variation in the complement C3 allotypes on the first-year allograft outcome after live donor liver transplantation.

Transpl Immunol 2020 06 17;60:101294. Epub 2020 Apr 17.

Department of Clinical Biochemistry and Molecular Diagnostics, National Liver Institute, Menoufia University, Egypt. Electronic address:

Background: The component (C3) of the complement system constitutes a central element in liver transplantation. C3 is produced mainly by the liver and comprises both slow (C3-S), and fast (C3-F) components.

Methods: The effect of a single nucleotide variation in the C3 gene on the first-year outcome examined by ARMS PCR in 30 recipients of living donor allograft.

Results: Frequencies of C3-S and C3-F in the Egyptian recipients' population were 67% and 33%. C3-F allele frequency was prevalent than the C3-S allele in recipients who developed acute rejection. The C3-SF and C3-FF genotypes significantly associated with acute rejection with 6.25 times increase in the risk of rejection than C3-SS (OR: 6.25; CI:1.05-37.07, p < .05). C3-SS increases the survival 2.5 times more than C3-SF or C3-FF but without significant association (OR: 0.40, CI: 0.07-2.44, p = .3). C3 genotypes or allotypes had no significant association with the recipient's survival, death, graft loss, infection, or serum levels of tacrolimus (all p > .05). C3-FF and C3-SF genotypes had the highest HCV recurrence rate but without significant association (p > .05).

Conclusion: In liver allograft recipients, C3-SF and C3-FF genotypes significantly associated with acute rejection with the C3-F allele more prevalent than the C3-S. C3-SS genotype increases survival without significant association.
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http://dx.doi.org/10.1016/j.trim.2020.101294DOI Listing
June 2020

A multimodal computer-aided diagnostic system for precise identification of renal allograft rejection: Preliminary results.

Med Phys 2020 Jun 3;47(6):2427-2440. Epub 2020 Apr 3.

Department of Bioengineering, University of Louisville, Louisville, KY, 40208, USA.

Purpose: Early assessment of renal allograft function post-transplantation is crucial to minimize and control allograft rejection. Biopsy - the gold standard - is used only as a last resort due to its invasiveness, high cost, adverse events (e.g., bleeding, infection, etc.), and the time for reporting. To overcome these limitations, a renal computer-assisted diagnostic (Renal-CAD) system was developed to assess kidney transplant function.

Methods: The developed Renal-CAD system integrates data collected from two image-based sources and two clinical-based sources to assess renal transplant function. The imaging sources were the apparent diffusion coefficients (ADCs) extracted from 47 diffusion-weighted magnetic resonance imaging (DW-MRI) scans at 11 different b-values (b0, b50, b100, ..., b1000 s/mm ), and the transverse relaxation rate (R2*) extracted from 30 blood oxygen level-dependent MRI (BOLD-MRI) scans at 5 different echo times (TEs = 2, 7, 12, 17, and 22 ms). Serum creatinine (SCr) and creatinine clearance (CrCl) were the clinical sources for kidney function evaluation. The Renal-CAD system initially performed kidney segmentation using the level-set method, followed by estimation of the ADCs from DW-MRIs and the R2* from BOLD-MRIs. ADCs and R2* estimates from 30 subjects that have both types of scans were integrated with their associated SCr and CrCl. The integrated biomarkers were then used as our discriminatory features to train and test a deep learning-based classifier, namely stacked autoencoders (SAEs) to differentiate non-rejection (NR) from acute rejection (AR) renal transplants.

Results: Using a leave-one-subject-out cross-validation approach along with SAEs, the Renal-CAD system demonstrated 93.3% accuracy, 90.0% sensitivity, and 95.0% specificity in differentiating AR from NR. Robustness of the Renal-CAD system was also confirmed by the area under the curve value of 0.92. Using a stratified tenfold cross-validation approach, the Renal-CAD system demonstrated its reproducibility and robustness by a diagnostic accuracy of 86.7%, sensitivity of 80.0%, specificity of 90.0%, and AUC of 0.88.

Conclusion: The obtained results demonstrate the feasibility and efficacy of accurate, noninvasive identification of AR at an early stage using the Renal-CAD system.
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http://dx.doi.org/10.1002/mp.14109DOI Listing
June 2020

Novel Polymethoxylated Chalcones as Potential Compounds Against KRAS-Mutant Colorectal Cancers.

Curr Pharm Des 2020 ;26(14):1622-1633

College of Pharmacy, QU Health, Qatar University, Doha, Qatar.

Background/objective: KRAS-mutant colorectal cancers (CRC) are tumors that are associated with poor prognosis. However, no effective treatments are available to target them. Therefore, we designed and synthesized novel chalcone analogs, small organic molecules, to investigate their effects on KRAS-mutant CRC cells.

Methods: Fourteen new chalcone analogs were synthesized, optimized, characterized, and tested against two KRAS-mutant CRC cell lines (HCT-116 and LoVo), one p-53 and BRAF mutant CRC cell line (HT-29) and one normal immortalized colon cells (NCE-1 E6/E7). Effects on cell viability, apoptosis, cell cycle, migration, colony formation, EMT, and angiogenesis were investigated.

Results: Compounds 3 and 14 were the most effective. Compound 3 showed potent activity against HCT-116 and LoVo cell lines (GI50 of 6.10 μM and 7.00 μM, respectively). While compound 14 showed GI50 of 8.60 μM and 8.80 μM on HCT-116 and LoVo cell lines, respectively. Both compounds were approximately 2-3 times more selective toward cancer cells rather than normal colon cells. Compound 3 was effective in inducing apoptosis in HCT-116 cells via Bax upregulation and Bcl-2 downregulation. Invasion and metastasis of KRAS-mutant cells were modulated by compounds 3 and 14 through significant inhibition of cell migration and the prevention of colony formation. In addition, they reversed EMT by downregulation of EMT markers (vimentin, fascin, and β- catenin) and upregulation of cell-cell adhesion marker, E-cadherin. Furthermore, compounds 3 and 14 had significantly inhibited angiogenesis in ovo.

Conclusion: Compounds 3 and 14 represent potent and selective leads for KRAS-mutant CRC cells, thus, further in vitro and in vivo studies are necessary to confirm their effect on KRAS-mutant CRCs.
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http://dx.doi.org/10.2174/1381612826666200206095400DOI Listing
November 2020

Design, synthesis, and validation of novel nitrogen-based chalcone analogs against triple negative breast cancer.

Eur J Med Chem 2020 Feb 7;187:111954. Epub 2019 Dec 7.

College of Pharmacy, Qatar Health, Qatar University, Doha, Qatar. Electronic address:

Great strides have been made in triple negative breast cancer (TNBC) treatment, which represents 20% of total predicted annual US breast cancer (BC) cases. Despite the development of several therapeutics, TNBC patients have poor overall survival rate, compared to other BC patients, justifying the urgent need to discover new entities for use to control TNBC. Chalcones are important natural products with diverse bioactivities including anticancer effects. This study aimed to design, synthesize and validate novel chalcone leads as potential therapies for TNBC. Fourteen novel chalcone analogs were designed and synthesized comprising alicyclic amines (pyrrolidine, morpholine and piperidine) or nitrogen mustard (Bis-(2-chloroethyl) amine) substituents. Among them, compound 14((E)-3-(4-(Bis(2-chloroethyl) amino) phenyl)-1-(3-methoxyphenyl) prop-2-en-1-one) was identified as the most effective against TNBC and other BC phenotypes, with anti-proliferative IC values ranging between 3.94 and 9.22 μM against the TNBC cell lines MDA-MB-231 and MDA-MB-468, as well as against the estrogen positive MCF-7 cell line. Chalcone 14 effectively suppressed the colony formation capacity of MDA-MB-231, MDA-MB-468, and MCF-7 cell lines at 5 and 10 μM treatment concentrations. Furthermore, compound 14 has significantly inhibited cell invasion and migration of MDA-MB-231 and MCF-7 BC cell lines. Additionally, compound 14 had significantly promoted apoptosis by upregulating BAX and downregulating Bcl-2 proteins. Compound 14 induced significant cell cycle arrest of TNBC cells at the G2/M phase. It also induced a reversal of Epithelial Mesenchymal Transition (EMT) by upregulating the epithelial markers E-cadherin and Pan-cadherin and downregulating FAK. Furthermore, it had dramatically diminished new vessel formation (vasculogenesis) in chick chorioallantoic membrane (CAM) model by 60.20 ± 8.47%. Chalcone 14 inhibited 46.41 ± 0.71% of the TNBC MAD-MB-231 cells growth in a nude mouse orthotopic xenograft model in comparison with vehicle control treated animals. Collectively, this study results propose chalcone 14 as a promising lead molecule for the control of TNBC as well as other breast cancer phenotypes.
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http://dx.doi.org/10.1016/j.ejmech.2019.111954DOI Listing
February 2020

A novel computer-aided diagnosis system for the early detection of hypertension based on cerebrovascular alterations.

Neuroimage Clin 2020 2;25:102107. Epub 2019 Dec 2.

Bioimaging Laboratory, J.B Speed School of Engineering, University of Louisville, KY, USA. Electronic address:

Hypertension is a leading cause of mortality in the USA. While simple tools such as the sphygmomanometer are widely used to diagnose hypertension, they could not predict the disease before its onset. Clinical studies suggest that alterations in the structure of human brains' cerebrovasculature start to develop years before the onset of hypertension. In this research, we present a novel computer-aided diagnosis (CAD) system for the early detection of hypertension. The proposed CAD system analyzes magnetic resonance angiography (MRA) data of human brains to detect and track the cerebral vascular alterations and this is achieved using the following steps: i) MRA data are preprocessed to eliminate noise effects, correct the bias field effect, reduce the contrast inhomogeneity using the generalized Gauss-Markov random field (GGMRF) model, and normalize the MRA data, ii) the cerebral vascular tree of each MRA volume is segmented using a 3-D convolutional neural network (3D-CNN), iii) cerebral features in terms of diameters and tortuosity of blood vessels are estimated and used to construct feature vectors, iv) feature vectors are then used to train and test various artificial neural networks to classify data into two classes; normal and hypertensive. A balanced data set of 66 subjects were used to test the CAD system. Experimental results reported a classification accuracy of 90.9% which supports the efficacy of the CAD system components to accurately model and discriminate between normal and hypertensive subjects. Clinicians would benefit from the proposed CAD system to detect and track cerebral vascular alterations over time for people with high potential of developing hypertension and to prepare appropriate treatment plans to mitigate adverse events.
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http://dx.doi.org/10.1016/j.nicl.2019.102107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6926373PMC
January 2021

Antitumor effect of insulin-like growth factor-1 receptor inhibition in head and neck squamous cell carcinoma.

Laryngoscope 2020 06 21;130(6):1470-1478. Epub 2019 Aug 21.

Department of Otolaryngology-Head and Neck Surgery, University of Virginia Health System, Charlottesville, Virginia, U.S.A.

Objectives: The insulin-like growth factor-1 receptor (IGF1R) has been implicated in therapeutic resistance in head and neck squamous cell carcinoma (HNSCC), and small molecule tyrosine kinase inhibitors (TKIs) of IGF1R activity may have anticancer activity. Therefore, the relationship between survival and IGF1R expression was assessed for oral cavity (OC) cancer, and the antitumor effects of two IGF1R-TKIs, OSI-906 and BMS-754807, were evaluated in HNSCC cell lines in vitro.

Methods: Clinical outcome data and tissue microarray immunohistochemistry were used to generate IGF1R expression-specific survival curves. Immunoblot, alamarBlue proliferation assay, trypan blue exclusion viability test, clonogenic assay, flow cytometry, and reverse phase protein array (RPPA) were used to evaluate in vitro responses to IGF1R-TKIs.

Results: For patients with stage III/IV OCSCC, higher IGF1R expression was associated with poorer overall 5-year survival (P = 0.029). Both BMS-754807 and OSI-906 caused dose-dependent inhibition of IGF1R and Akt phosphorylation and inhibited proliferation; BMS-754807 was more potent than OSI-906. Both drugs reduced HNSCC cell viability; only OSI-906 was able to eliminate all viable cells at 10 μM. The two drugs similarly inhibited clonogenic cell survival. At 1 μM, only BMS-754807 caused a fourfold increase in the basal apoptotic rate. RPPA demonstrated broad effects of both drugs on canonical IGF1R signaling pathways and also inhibition of human epidermal growth factor receptor-3 (HER3), Src, paxillin, and ezrin phosphorylation.

Conclusion: OSI-906 and BMS-754807 inhibit IGF1R activity in HNSCC cell lines with reduction in prosurvival and proliferative signaling and with concomitant antiproliferative and proapoptotic effects. Such antagonists may have utility as adjuvants to existing therapies for HNSCC.

Level Of Evidence: NA Laryngoscope, 130:1470-1478, 2020.
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http://dx.doi.org/10.1002/lary.28236DOI Listing
June 2020

SAR and molecular mechanism studies of monoamine oxidase inhibition by selected chalcone analogs.

J Enzyme Inhib Med Chem 2019 Dec;34(1):863-876

a Department of Pharmaceutical Sciences, College of Pharmacy , Qatar University , Doha , Qatar.

The present study describes the synthesis of a series of 22 chalcone analogs. These compounds were evaluated as potential human MAO-A and MAO-B inhibitors. The compounds showed varied selectivity against the two isoforms. The IC values were found to be in the micromolar to submicromolar range. The K values of compound 16 were determined to be 0.047 and 0.020 μM for the inhibition of MAO-A and MAO-B, respectively. Dialysis of enzyme-inhibitor mixtures indicated a reversible competitive mode of inhibition. Most of the synthesized chalcone analogs showed a better selectivity toward MAO-B. However, introducing of 2,4,6-trimethoxy substituents on ring B shifted the selectivity toward MAO-A. In addition, we investigated the molecular mechanism of MAO-B inhibition by selected chalcone analogs. Our results revealed that these selected chalcone analogs increased dopamine levels in the rat hepatoma (H4IIE) cells and decreased the relative mRNA expression of the MAO-B enzyme.
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http://dx.doi.org/10.1080/14756366.2019.1593158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442233PMC
December 2019

Survivin in Insulin-Like Growth Factor-Induced Resistance to Lapatinib in Head and Neck Squamous Carcinoma Cells.

Front Oncol 2019 23;9:13. Epub 2019 Jan 23.

Division of Head and Neck Oncologic and Microvascular Surgery, Department of Otolaryngology-Head and Neck Surgery, University of Virginia Health System, Charlottesville, VA, United States.

Epidermal growth factor receptor (EGFR) inhibitors have limited efficacy in head and neck squamous cell carcinoma (HNSCC) due to various resistance mechanisms, such as activation of the insulin-like growth factor-1 receptor (IGF1R), which initiates pro-survival signaling. Survivin, a member of the inhibitor of apoptosis proteins family, is expressed at relatively high levels in malignant tissues and plays a role in cell division. Expression of survivin in tumors has been shown to correlate with poor prognosis due to chemotherapy resistance and anti-apoptotic behavior. We previously demonstrated that activation of the IGF1R reduces sensitivity to EGFR-tyrosine kinase inhibitors (TKIs) via reduced apoptosis suggesting a role of survivin in this process. This study evaluates the role of survivin in IGF1R-mediated lapatinib resistance. Using HNSCC cell lines FaDu and SCC25, survivin expression increased and lapatinib sensitivity decreased with IGF1R activation. Further, these effects were reversed by the survivin inhibitor YM-155. Conversely, survivin expression and lapatinib sensitivity were unchanged with IGF1R activation in UNC10 cells. YM-155 enhanced the inhibitory effect of lapatinib on UNC10 cells, regardless of activation of the IGF1R. These results demonstrate that enhanced survivin expression correlates with IGF1R-mediated lapatinib resistance in HNSCC cells and suggest that regulation of survivin expression may be a key mechanistic element in IGF1R-based therapeutic resistance. Combinatorial treatment with survivin antagonists and EGFR-TKIs warrants further investigation.
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http://dx.doi.org/10.3389/fonc.2019.00013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351440PMC
January 2019

Teucrium Polium Plant Extract Provokes Substantial Cytotoxicity at the Early Stage of Embryonic Development.

Bosn J Basic Med Sci 2019 Feb 12;19(1):67-71. Epub 2019 Feb 12.

College of Medicine, Qatar University; Biomedical Research Centre, Qatar University, Doha, Qatar.

The aim of this study is to explore the outcome of Teucrium polium (TP) medicinal plant consumption on the early stage of fetal development. We used the chicken embryo at 3 days of incubation as a model to evaluate the effect of TP plant extract during embryogenesis. In addition, quantitative polymerase chain reaction (qPCR) was applied to explore the expression of six genes related to cell proliferation, apoptosis, sur-vival, angiogenesis, and migration. Our data revealed that TP exposure inhibits angiogenesis of the chicken embryo and its chorioallantoic membrane. In addition, we found that TP extract significantly harms the normal development of the embryos since around 95% of TP-exposed embryos died after 1-3 days of treatment. Macroscopic examination did not show any anomalies in these embryos. However, qPCR analysis of activation transcription factor-3, B-cell lymphoma-2, caspase 8, inhibin subunit beta A, vascular endothelial growth factor-C, and Cadherin-6 type-2 genes revealed that these genes are considerably deregulated in heart and brain tissues from TP-exposed embryos in comparison with their matched tissues from unexposed ones. Our study implies that TP plant can have very toxic effects on the early stage of the embryo. Therefore, it is important to alert expectant women to avoid the use of this medicinal plant during pregnancy.
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http://dx.doi.org/10.17305/bjbms.2018.4052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387674PMC
February 2019

The Role of Diuretics in Treatment of Aromatase Inhibitors Induced Musculoskeletal Symptoms in Women with Non Metastatic Breast Cancer

Asian Pac J Cancer Prev 2018 Dec 25;19(12):3525-3531. Epub 2018 Dec 25.

Department of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Menoufia University, Shebin El kom, Egypt. Email:

Background: Around 50% of women receiving Aromatase Inhibitors (AIs) develop musculoskeletal symptoms which may become severe causing interruption of treatment. Patients with AI-induced arthralgia had higher rates of joint effusions and fluid in the tendons, so use of diuretics may be helpful. Methods: This prospective phase II study was conducted in department of clinical oncology and nuclear medicine, Menoufia University Hospital, Egypt, between Jan. to Dec. 2015. Fifty Women with stage I,II and III breast cancer receiving AIs as adjuvant hormonal treatment complaining of AIs related musculoskeletal symptoms received Lasilactone® 50 mg tablet; (an oral combination of Frusemide 20mg/Spironolactone 50 mg), every other day for 4 weeks. Patients were assessed by modified Western Ontario and McMaster Universities osteoarthritis (WOMAC) index for lower limb and the quick Disabilities of the Arm, Shoulder and Hand Score (DASH) scoring system for upper limbs, Arabic versions, at baseline and after 4 weeks of treatment. Results: The mean WOMAC pain score improved significantly (6.0 v 10; P < 0.001), the mean WOMAC stiffness score improved (2.3 v 3.9; P = 0.002), the mean WOMAC functional score improved (8.7 v 15; P < 0.001), the total WOMAC score improved (17 v 29; P < 0.001), also a significant difference was noticed for the quick DASH score; total score (16 v 25; P = 0.02) After use of diuretics for 4 weeks of treatment compared with baseline scores. Conclusions: The use of diuretics effectively reduces AI related musculoskeletal symptoms with good tolerance.
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http://dx.doi.org/10.31557/APJCP.2018.19.12.3525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428535PMC
December 2018

Targeting triple negative breast cancer heterogeneity with chalcones: a molecular insight.

J Drug Target 2019 09 11;27(8):830-838. Epub 2019 Feb 11.

a College of Pharmacy , Qatar University , Doha , Qatar.

Triple negative breast cancers (TNBCs) are aggressive heterogeneous cancers with not yet determined conventional targeted medication. Therefore, identification of new alternatives or improved treatment options to combat this deadly disease is highly needed. On the other hand, various derived products with chalcone scaffold were historically considered excellent candidates for the development of anticancer drugs. Chalcones unique chemical structure and their substantial biological activities in cancer cells make them an extremely attractive target for the treatment of several human carcinomas including TNBCs. This review highlights the promising therapeutic role of chalcones in TNBC management.
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http://dx.doi.org/10.1080/1061186X.2018.1561889DOI Listing
September 2019

GDF11 Decreases Pressure Overload-Induced Hypertrophy, but Can Cause Severe Cachexia and Premature Death.

Circ Res 2018 11;123(11):1220-1231

From the Cardiovascular Research Center (S.C.H., J.J., G.B., T.W., M.W., H.K., E.A.F., Y.Y., Y.J., X.G., A.K.S., S.R.H.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA.

Rationale: Possible beneficial effects of GDF11 (growth differentiation factor 11) on the normal, diseased, and aging heart have been reported, including reversing aging-induced hypertrophy. These effects have not been well validated. High levels of GDF11 have also been shown to cause cardiac and skeletal muscle wasting. These controversies could be resolved if dose-dependent effects of GDF11 were defined in normal and aged animals as well as in pressure overload-induced pathological hypertrophy.

Objective: To determine dose-dependent effects of GDF11 on normal hearts and those with pressure overload-induced cardiac hypertrophy.

Methods And Results: Twelve- to 13-week-old C57BL/6 mice underwent transverse aortic constriction (TAC) surgery. One-week post-TAC, these mice received rGDF11 (recombinant GDF11) at 1 of 3 doses: 0.5, 1.0, or 5.0 mg/kg for up to 14 days. Treatment with GDF11 increased plasma concentrations of GDF11 and p-SMAD2 in the heart. There were no significant differences in the peak pressure gradients across the aortic constriction between treatment groups at 1 week post-TAC. Two weeks of GDF11 treatment caused dose-dependent decreases in cardiac hypertrophy as measured by heart weight/tibia length ratio, myocyte cross-sectional area, and left ventricular mass. GDF11 improved cardiac pump function while preventing TAC-induced ventricular dilation and caused a dose-dependent decrease in interstitial fibrosis (in vivo), despite increasing markers of fibroblast activation and myofibroblast transdifferentiation (in vitro). Treatment with the highest dose (5.0 mg/kg) of GDF11 caused severe body weight loss, with significant decreases in both muscle and organ weights and death in both sham and TAC mice.

Conclusions: Although GDF11 treatment can reduce pathological cardiac hypertrophy and associated fibrosis while improving cardiac pump function in pressure overload, high doses of GDF11 cause severe cachexia and death. Use of GDF11 as a therapy could have potentially devastating actions on the heart and other tissues.
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http://dx.doi.org/10.1161/CIRCRESAHA.118.312955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309347PMC
November 2018

Downregulation of IGF1R Expression Inhibits Growth and Enhances Cisplatin Sensitivity of Head and Neck Squamous Cell Carcinoma Cells In Vitro.

Horm Cancer 2019 02 23;10(1):11-23. Epub 2018 Oct 23.

Department of Otolaryngology - Head and Neck Surgery, Division of Head and Neck Oncologic and Microvascular Surgery, University of Virginia Health System, Charlottesville, VA, USA.

A lentivirus-mediated doxycycline-inducible pTRIPZ shRNAmir plasmid targeting IGF1R transcript was transfected into two head and neck squamous cell carcinoma (HNSCC) cell lines to silence IGF1R expression and to assess the effect of its downregulation on cisplatin sensitivity in vitro. In Cal27-regIGF1R and SCC25-regIGF1R cell lines, IGF1R protein expression was reduced by more than 90% after 72 h of incubation with doxycycline. Both basal and IGF-stimulated pIGF1R, pAKT, and pERK were significantly reduced, without influence on total AKT and ERK expression. Downregulation of the IGF1R was associated with decreased proliferation and cell viability in both cell lines. Reduced IGF1R expression was also associated with increased sub-G0/G1-phase and G0/G1-phase populations and decreased S-phase and G2/M-phase populations. IGF1R downregulation enhanced sensitivity to cisplatin with decrease of cisplatin IC from 15 to 7.1 in Cal27-regIGF1R cells and from 11 to 6.3 in SCC25-regIGF1R cells. Cisplatin exhibited increased pro-apoptotic activity by annexin V staining and PARP cleavage in both cells lines when cultured in doxycycline. Thus, in two HNSCC cell lines in vitro, reduced IGF1R expression results in reduced growth rate and increased sensitivity to cisplatin. Thus, IGF1R downregulation and/or inhibition may serve as a useful adjunct to platinum-based cytotoxic chemotherapy.
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http://dx.doi.org/10.1007/s12672-018-0352-7DOI Listing
February 2019

Could Araucaria heterophylla resin extract be used as a new treatment for toxoplasmosis?

Exp Parasitol 2018 Dec 16;195:44-53. Epub 2018 Oct 16.

Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.

Toxoplasmosis is a worldwide parasitic disease responsible for serious health problems to human. The currently available drugs used for toxoplasmosis treatment showed a limited efficacy and cause serious host toxicity. The in vitro screening for toxoplasmicidal activity of Araucaria heterophylla resin (AHR) extract and its major component 13-epi-cupressic acid (CUP) showed that both AHR (EC = 3.90) and CUP (EC = 3.69) have high toxoplasmicidal activity in comparison with standard cotrimoxazole (EC = 4.28). The antiprotozoal effects of AHR and CUP were investigated against acute and chronic toxoplasmosis using mice models. Two groups of Swiss albino mice were infected by RH Toxoplasma strain intraperitoneally and by Me49 strain orally. Both groups were treated with AHR and CUP in different doses. Their effects were evaluated by survival rate, peritoneal, spleen and liver parasite burdens, brain cyst burden, NO serum level and histopathological lesions. The ultrastructural changes of tachyzoites of acutely infected mice were studied using scanning electron microscopy (SEM). There is an evidence of toxoplasmicidal activity of AHR and CUP in acute and chronic experimental toxoplasmosis. In the acute model, mice treated with AHR and CUP showed prolonged survival rates, a significant decrease in the parasite density in peritoneal lavage and pathological insult in both liver and spleen compared with that of untreated ones. SEM results denote evident morphological alterations of treated tachyzoites. In chronic experimental toxoplasmosis, AHR and CUP treated groups could significantly reduce brain cyst burden by 96.05% and 98.02% respectively. This study indicates that AHR and CUP showed potent toxoplasmicidal activities experimentally and could be used as a potential natural nontoxic agent for treatment of toxoplasmosis.
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http://dx.doi.org/10.1016/j.exppara.2018.10.003DOI Listing
December 2018

Deep Learning Role in Early Diagnosis of Prostate Cancer.

Technol Cancer Res Treat 2018 01;17:1533034618775530

2 Department of Bioengineering, University of Louisville, Louisville, KY, USA.

The objective of this work is to develop a computer-aided diagnostic system for early diagnosis of prostate cancer. The presented system integrates both clinical biomarkers (prostate-specific antigen) and extracted features from diffusion-weighted magnetic resonance imaging collected at multiple b values. The presented system performs 3 major processing steps. First, prostate delineation using a hybrid approach that combines a level-set model with nonnegative matrix factorization. Second, estimation and normalization of diffusion parameters, which are the apparent diffusion coefficients of the delineated prostate volumes at different b values followed by refinement of those apparent diffusion coefficients using a generalized Gaussian Markov random field model. Then, construction of the cumulative distribution functions of the processed apparent diffusion coefficients at multiple b values. In parallel, a K-nearest neighbor classifier is employed to transform the prostate-specific antigen results into diagnostic probabilities. Finally, those prostate-specific antigen-based probabilities are integrated with the initial diagnostic probabilities obtained using stacked nonnegativity constraint sparse autoencoders that employ apparent diffusion coefficient-cumulative distribution functions for better diagnostic accuracy. Experiments conducted on 18 diffusion-weighted magnetic resonance imaging data sets achieved 94.4% diagnosis accuracy (sensitivity = 88.9% and specificity = 100%), which indicate the promising results of the presented computer-aided diagnostic system.
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http://dx.doi.org/10.1177/1533034618775530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972199PMC
January 2018

A Diagnostic Laboratory-Based Study on Frequency and Distribution of Viral Hepatitis B and C Among Sudanese.

Open Virol J 2017 31;11:98-107. Epub 2017 Oct 31.

Almokhtabar Moamena Kamel Medical Laboratories, Khartoum, Sudan.

Background: Hepatitis B infection is an alarming public health problem. Almost two billion people of the population alive today, would have been infected at some time in their lives by hepatitis B. Hepatitis C virus is another life threatening condition, and about 425,000 deaths occur each year due to its complications.The current study was carried out to provide care givers and health planners basic epidemiological data regarding the frequency and distribution of HBV and HCV based on age and sex during a time period of more than 5 years.

Result: A total of 2109 different patients were found to be infected by HBV during the study period; 1641 (77.81%) were males and 468 (22.19%) were females with the age group of 20-39 years predominating (64%). In addition,16% of patients tested for HBeAg were found reactive.

Conclusion: There were significant correlations observed between the levels of HBV DNA and ALT, AST and AFP. Regarding HCV, 70 males (54.9%) and 63 females (45.1%) were found to be infected, with preponderance of the age group 41 - 60 years and the genotype 4. Designing knowledge raising campaigns is appreciated as well as repetition of similar studies among larger populations in the following few years will help track a way to improvement.
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http://dx.doi.org/10.2174/1874357901711010098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5769029PMC
October 2017

Fracture Resistance of Tilted Premolars Restored with Different Post-Core Systems.

J Int Soc Prev Community Dent 2017 Nov-Dec;7(6):344-350. Epub 2017 Dec 29.

Internship Program, College of Dentistry, King Khalid University, Abha, Saudi Arabia.

Aims And Objective: To assess the effect of root tilt on the fracture resistance and failure pattern of endodontically-treated premolars restored with different post-core systems.

Materials And Methods: Ninety endodontically-treated premolars were mounted in acrylic blocks with 0°, 12°, and 24° axial root tilt. Teeth in each group were restored in three subgroups with cast post-core, readymade metal posts and composite cores, and fiber post and composite cores. Crowns of all teeth were prepared coinciding with the long axis of the acrylic blocks to receive all-ceramic crowns. All restored teeth were stressed to record the maximum load at failure and the associated failure pattern. The collected data were statistically analyzed using two-way ANOVA, Tukey's, and Kruskal-Wallis tests at α = 0.05 on past software to detect any differences between subgroups.

Results: Analysis of the collected data indicated significant differences between the tested subgroups (ANOVA, = 3.86). Further analysis showed significant difference between all test subgroups and the control (Tukey's, < 0.05). In general, teeth with 0° tilt seemed more resistant to fracture than the tilted ones. For all groups, teeth restored with fiber post and composite cores (SG3) were more resistant to fracture compared to other post-core systems (SG1 and SG2) (Tukey's, < 0.05). The root fracture was the most commonly seen mode of failure.

Conclusions: Root tilting usually affects the fracture resistance of teeth restored with post-core systems. The fiber post and composite cores seemed to be the best choice to restore teeth with different root tilting possibilities.
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http://dx.doi.org/10.4103/jispcd.JISPCD_382_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774055PMC
December 2017

A Novel Early Diagnosis System for Mild Cognitive Impairment Based on Local Region Analysis: A Pilot Study.

Front Hum Neurosci 2017 9;11:643. Epub 2018 Jan 9.

Department of Computer Science and Information Technology, College of Engineering, Abu Dhabi University, Abu Dhabi, United Arab Emirates.

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder that accounts for 60-70% of cases of dementia in the elderly. An early diagnosis of AD is usually hampered for many reasons including the variable clinical and pathological features exhibited among affected individuals. This paper presents a computer-aided diagnosis (CAD) system with the primary goal of improving the accuracy, specificity, and sensitivity of diagnosis. In this system, PiB-PET scans, which were obtained from the ADNI database, underwent five essential stages. First, the scans were standardized and de-noised. Second, an Automated Anatomical Labeling (AAL) atlas was utilized to partition the brain into 116 regions or labels that served for local (region-based) diagnosis. Third, scale-invariant Laplacian of Gaussian (LoG) was used, per brain label, to detect the discriminant features. Fourth, the regions' features were analyzed using a general linear model in the form of a two-sample -test. Fifth, the support vector machines (SVM) and their probabilistic variant (pSVM) were constructed to provide local, followed by global diagnosis. The system was evaluated on scans of normal control (NC) vs. mild cognitive impairment (MCI) (19 NC and 65 MCI scans). The proposed system showed superior accuracy, specificity, and sensitivity as compared to other related work.
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http://dx.doi.org/10.3389/fnhum.2017.00643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5767309PMC
January 2018

A fast stochastic framework for automatic MR brain images segmentation.

PLoS One 2017 14;12(11):e0187391. Epub 2017 Nov 14.

Bioengineering Department, University of Louisville, Louisville, KY, United States of America.

This paper introduces a new framework for the segmentation of different brain structures (white matter, gray matter, and cerebrospinal fluid) from 3D MR brain images at different life stages. The proposed segmentation framework is based on a shape prior built using a subset of co-aligned training images that is adapted during the segmentation process based on first- and second-order visual appearance characteristics of MR images. These characteristics are described using voxel-wise image intensities and their spatial interaction features. To more accurately model the empirical grey level distribution of the brain signals, we use a linear combination of discrete Gaussians (LCDG) model having positive and negative components. To accurately account for the large inhomogeneity in infant MRIs, a higher-order Markov-Gibbs Random Field (MGRF) spatial interaction model that integrates third- and fourth- order families with a traditional second-order model is proposed. The proposed approach was tested and evaluated on 102 3D MR brain scans using three metrics: the Dice coefficient, the 95-percentile modified Hausdorff distance, and the absolute brain volume difference. Experimental results show better segmentation of MR brain images compared to current open source segmentation tools.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0187391PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5685492PMC
December 2017

The EGFR Inhibitor Gefitinib Enhanced the Response of Human Oral Squamous Cell Carcinoma to Cisplatin In Vitro.

Drugs R D 2017 Dec;17(4):545-555

Division of Head and Neck Oncologic and Microvascular Surgery, Department of Otolaryngology-Head and Neck Surgery, University of Virginia Health System, Charlottesville, VA, USA.

Introduction: The epidermal growth factor receptor (EGFR) is highly expressed in a variety of solid tumors including oral cavity squamous cell carcinoma (OSCC) and has been implicated in the resistance of these tumors to cisplatin. This study was performed to determine if the EGFR tyrosine kinase inhibitor gefitinib could enhance the cytotoxic effect of cisplatin on OSCC cells in vitro.

Methods: The expression of EGFR and the phosphorylation of its downstream signaling to ERK, and AKT pathway were detected by Western blotting. Cell proliferation and survival were determined by AlamarBlue and colony formation assay respectively. Cells apoptosis were determined by Western blotting for cleaved PARP protein and by flowcytometry of cells stained with Annexin V and PI.

Results: Cal27, OSC19, and SCC25 cells treated with gefitinib 1 μM demonstrated reduced phosphorylation of EGFR, AKT, and ERK proteins with very limited inhibition of proliferation. Cisplatin inhibited proliferation of the same cell lines in a dose-dependent manner. The concentration producing 50% inhibition (IC) for cisplatin decreased in the presence of gefitinib 1 μM, and a combination of cisplatin 5 µM and gefitinib 1 µM caused synergistic growth inhibition and synergistic reduction in cell survival. The growth inhibitory effect of the combination was associated with reduced ERK and AKT activation, increased poly ADP ribose polymerase (PARP) cleavage, and increased apoptosis.

Conclusion: Thus, in OSCC cells in vitro, inhibition of EGFR activity with gefitinib enhances the apoptotic effect of cisplatin. This has potential implications for enhancement of cisplatin effectiveness in tumors that over-express the EGFR.
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http://dx.doi.org/10.1007/s40268-017-0204-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5694417PMC
December 2017

Predictive control strategy of a gas turbine for improvement of combined cycle power plant dynamic performance and efficiency.

Springerplus 2016 4;5(1):980. Epub 2016 Jul 4.

Production Department, General Electric Company of Libya, Tripoli, Libya.

This paper presents a novel strategy for implementing model predictive control (MPC) to a large gas turbine power plant as a part of our research progress in order to improve plant thermal efficiency and load-frequency control performance. A generalized state space model for a large gas turbine covering the whole steady operational range is designed according to subspace identification method with closed loop data as input to the identification algorithm. Then the model is used in developing a MPC and integrated into the plant existing control strategy. The strategy principle is based on feeding the reference signals of the pilot valve, natural gas valve, and the compressor pressure ratio controller with the optimized decisions given by the MPC instead of direct application of the control signals. If the set points for the compressor controller and turbine valves are sent in a timely manner, there will be more kinetic energy in the plant to release faster responses on the output and the overall system efficiency is improved. Simulation results have illustrated the feasibility of the proposed application that has achieved significant improvement in the frequency variations and load following capability which are also translated to be improvements in the overall combined cycle thermal efficiency of around 1.1 % compared to the existing one.
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http://dx.doi.org/10.1186/s40064-016-2679-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5396491PMC
July 2016

Structure-activity relationship of piperine and its synthetic amide analogs for therapeutic potential to prevent experimentally induced ER stress in vitro.

Cell Stress Chaperones 2017 05 10;22(3):417-428. Epub 2017 Apr 10.

College of Pharmacy, Qatar University, PO Box 2713, Doha, Qatar.

Endoplasmic reticulum (ER) is the key organelle involved in protein folding and maturation. Emerging studies implicate the role of ER stress in the development of chronic kidney disease. Thus, there is an urgent need for compounds that could ameliorate ER stress and prevent CKD. Piperine and its analogs have been reported to exhibit multiple pharmacological activities; however, their efficacy against ER stress in kidney cells has not been studied yet. Hence, the goal of this study was to synthesize amide-substituted piperine analogs and screen them for pharmacological activity to relieve ER stress using an in vitro model of tunicamycin-induced ER stress using normal rat kidney (NRK-52E) cells. Five amide-substituted piperine analogs were synthesized and their chemical structures were elucidated by pertinent spectroscopic techniques. An in vitro model of ER stress was developed using tunicamycin, and the compounds of interest were screened for their effect on cell viability, and the expression of ER chaperone GRP78, the pro-apoptotic ER stress marker CHOP, and apoptotic caspases 3 and 12 (via western blotting). Our findings indicate that exposure to tunicamycin (0.5 μg/mL) for 2 h induces the expression of GRP78 and CHOP, and apoptotic markers (caspase-3 and caspase-12) and causes a significant reduction in renal cell viability. Pre-treatment of cells with piperine and its cyclohexylamino analog decreased the tunicamycin-induced upregulation of GRP78 and CHOP and cell death. Taken together, our findings demonstrate that piperine and its analogs differentially regulate ER stress, and thus represent potential therapeutic agents to treat ER stress-related renal disorders. Graphical Abstract Piperine (PIP) reduces the expression of ER stress markers (GRP78 and CHOP) induced by pathologic stimuli and consequently decreases the activation of apoptotic caspase-12 and caspase-3; all of which contributes to its chemical chaperone and cytoprotective properties to protect renal cells against ER stress and ER stress-induced cell death, and would ultimately prevent the development of chronic kidney disease.
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http://dx.doi.org/10.1007/s12192-017-0786-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5425373PMC
May 2017

Response to: Comment to "No-Drain Single Incision Liposuction Pull-Through Technique for Gynecomastia".

Aesthetic Plast Surg 2017 08 3;41(4):992. Epub 2017 Apr 3.

Cairo University, Cairo, Egypt.

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http://dx.doi.org/10.1007/s00266-017-0857-4DOI Listing
August 2017