29 results on '"N. Haddadi"'
Search Results
2. 133 UVB-induced type-I interferon in keratinocytes is associated with expansion of CXCL13+ skin-resident memory T cells in dermatomyositis skin
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K. Afshari, Y. Wang, N. Haddadi, S. Sherman, J. Richmond, R. Vleugels, M. Garber, and M. Rashighi
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Cell Biology ,Dermatology ,Molecular Biology ,Biochemistry - Published
- 2023
3. 140 Comparative scRNA-Seq profiling of four autoimmune skin diseases points to CXCL13 as a potential player in skin autoimmunity
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Y. Wang, K. Afshari, M. Frisoli, N. Haddadi, S. Sherman, J.E. Harris, M. Rashighi, and M. Garber
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Cell Biology ,Dermatology ,Molecular Biology ,Biochemistry - Published
- 2023
4. 109 Bidirectional TGF-beta signaling between CD8+ T cells and melanocytes determines melanocyte death in vitiligo
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S. Sherman, E. Katz, K. Okamura, S. Shan, Y. Wang, K. Afshari, N. Haddadi, M. Garber, and J.E. Harris
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Cell Biology ,Dermatology ,Molecular Biology ,Biochemistry - Published
- 2023
5. 1178 Mechanisms of type I interferon-mediated UVB sensitivity in human keratinocytes
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N. Haddadi, K. Afshari, Y. Wang, S. Sherman, M. Garber, R. Vleugels, M.H. Orzalli, and M. Rashighi
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Cell Biology ,Dermatology ,Molecular Biology ,Biochemistry - Published
- 2023
6. Optimal Control of Delay Systems by Using a Hybrid Functions Approximation.
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N. Haddadi, Yadollah Ordokhani, and Mohsen Razzaghi
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- 2012
- Full Text
- View/download PDF
7. LB868 Th2 skewing promotes the expression of skin-homing molecules on T cells and is required for the induction of skin lesions in lupus-prone mice
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N. Haddadi, P. Mande, T. Brodeur, K. Hao, G. Ryan, S. Moses, S. Subramanian, X. Picari, K. Afshari, A. Marshak-Rothstein, and J.M. Richmond
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Cell Biology ,Dermatology ,Molecular Biology ,Biochemistry - Published
- 2022
8. 021 CXCL13-producing peripheral T helper cells as potential mediators of photosensitivity in dermatomyositis
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K. Afshari, N. Haddadi, Y. Wang, J.M. Richmond, R. Vleugels, M. Garber, and M. Rashighi
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Cell Biology ,Dermatology ,Molecular Biology ,Biochemistry - Published
- 2022
9. 828 Targeted proteomics and spectral flow cytometry analysis of cutaneous lupus erythematosus
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N. Haddadi, H.S. Raef, K. Afshari, M. Ahmed Refat, E. Kim, J. Galindo de Laflin, J. Harris, M. Rashighi, and J.M. Richmond
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Cell Biology ,Dermatology ,Molecular Biology ,Biochemistry - Published
- 2022
10. Core Muscles Endurance in Sedentary Individuals with and without Nonspecific Chronic Low Back: A Cross-Sectional Study
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N. Haddadi Esfahani, Z. Sadat Rezaeian, and Jan Dommerholt
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medicine.medical_specialty ,Physical medicine and rehabilitation ,Cross-sectional study ,business.industry ,medicine ,Orthopedics and Sports Medicine ,business ,Low back - Published
- 2021
11. Core Muscles Endurance in Sedentary Staffs with and without Nonspecific Chronic Low Back: A Cross-sectional Study.
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Esfahani, N. Haddadi, Dommerholt, J., and Rezaeian, Z. Sadat
- Subjects
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LUMBAR pain , *CHRONIC pain , *SEDENTARY lifestyles , *MCGILL Pain Questionnaire , *ANALYSIS of variance , *CROSS-sectional method , *TORSO , *SELF-evaluation , *PHYSICAL fitness , *MUSCLE strength testing , *OCCUPATIONS , *COMPARATIVE studies , *SITTING position , *DESCRIPTIVE statistics , *QUESTIONNAIRES , *ABDOMINAL exercises , *BACK exercises - Abstract
Background. Musculoskeletal dysfunction is one of the most important occupational health issues. Prolonged sitting may be a risk factor for low back pain (LBP) associated with reduced muscle endurance, although many people with a sedentary lifestyle and sitting-type job report no pain and discomfort in the lumbar region. In the present study, endurance of the core muscles in individuals with sedentary jobs with nonspecific chronic LBP were compared with those without LBP. Objective. The present study compared core muscle endurance in individuals with sedentary jobs with and without nonspecific chronic low back pain. Methods. A total of 50 sedentary staffs were selected and divided into LBP and control group. Trunk muscle endurance was measured in seconds using the McGill's trunk flexor endurance test, the Sorenson's trunk extensor endurance test, and the right and left trunk flexor endurance test (Side-bridge test). Differences between the two groups were analyzed using multivariate general linear models in 2 ways ANOVA. Results. There were no significant between-group differences in the raw endurance of the extensor, flexor, right/ left flexor muscles (P ≥ 0.05). However, there were significant between-group differences in some self-reported physical fitness subscales (P < 0.05), duration of sitting at home (P = 0.035), frequency of assuming a slump sitting position (P = 0.049), and sitting with leaning back to the backrest (P = 0.02) at work. We developed uni- and multivariate general linear models, which showed adjustments to these parameters and unmasked fundamental between-group differences in extensor muscle endurance. Conclusions. Our finding does not support the popular opinion that daily sitting-while-at-work for long durations is necessarily associated with LBP. Instead, sitting posture, lower physical fitness levels, and shorter duration of sitting activities at home may be associated with reduced extensor muscle endurance in nonspecific chronic low back pain. [ABSTRACT FROM AUTHOR]
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- 2021
- Full Text
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12. Optimal Control of Delay Systems by Using a Hybrid Functions Approximation
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Mohsen Razzaghi, Yadollah Ordokhani, and N. Haddadi
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Mathematical optimization ,Control and Optimization ,Applied Mathematics ,Numerical analysis ,Management Science and Operations Research ,Cross product ,Optimal control ,Bernoulli polynomials ,Algebraic equation ,symbols.namesake ,Quadratic equation ,Product (mathematics) ,ComputingMethodologies_SYMBOLICANDALGEBRAICMANIPULATION ,Theory of computation ,symbols ,Mathematics - Abstract
In this paper, a new numerical method for solving the optimal control of linear time-varying delay systems with quadratic performance index is presented. The method is based upon hybrid functions approximation. The properties of hybrid functions, consisting of block-pulse functions and Bernoulli polynomials, are presented. The operational matrices of integration, product, delay and the integration of the cross product of two hybrid functions of block-pulse and Bernoulli polynomials vectors are given. These matrices are then utilized to reduce the solution of the optimal control of delay systems to the solution of algebraic equations. Illustrative examples are included to demonstrate the validity and applicability of the technique.
- Published
- 2011
13. Regional geology and petroleum systems of the Illizi–Berkine area of the Algerian Saharan Platform: An overview
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O. Point, J. Mather, N. Haddadi, S. Galeazzi, and D. Druesne
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Paleozoic ,Stratigraphy ,Geology ,Orogeny ,Structural basin ,Oceanography ,Paleontology ,Gondwana ,Geophysics ,Source rock ,Phanerozoic ,Ordovician ,Economic Geology ,Sedimentary rock - Abstract
The Berkine and Illizi basins are Palaeozoic–Mesozoic intraplate depressions that preserve an over 7000 m thick sedimentary rock record and contain world-class petroleum systems with over 39 BBOE EUR hydrocarbon reserves. Regional seismic transects and a wealth of well data are used to review the tectonostratigraphic evolution of the area. The Gondwana (Palaeozoic) and Tethys (Mesozoic) supercycles make up the bulk of the Phanerozoic succession. These 1st order cycles record extensional basin formation, followed by a protracted period of overall net subsidence, and conclude with basin inversion and regional uplift during the Hercynian and Alpine orogenies respectively. Structural styles were dictated by transpressional or transtensional reactivation of mostly NNE oriented basement structural grain of Late Proterozoic–Ea.Cambrian (Pan-African) age and vertical movement of long wavelength regional highs and lows. Local tectonism is considered to be the far-field effect of plate-tectonic processes that affected the North African plate-boundaries, such as the Caledonian and Hercynian Orogenies, the opening of the Tethys and Atlantic oceans, and the Alpine Orogeny. These were accompanied by localised thermal mantle processes. Regional unconformities subdivide the Gondwana and Tethys supercycles into eight and seven megasequences respectively. These regional units often record 2nd order transgressive–regressive cycles that constrain the mapping of reservoir-seal pairs and of main source rock intervals. The lower Palaeozoic megasequences are characterised by sand-rich laterally extensive coarse-grained fluvial and shallow marine reservoirs interbedded with thin and widespread marine shales. They were mostly deposited in shorelines of shallow epeiric seas and continental braided river systems, or during the Late Ordovician, in a short-lived continental glacial system. Third order sequences display ramp-style geometries with largely parallel to low-angle sigmoidal stratal patterns. Early Mesozoic sedimentation followed the Late Palaeozoic uplift and peneplanation in the form of hinterland sequences containing fluvial and alluvial sandstones and playa-lake mudstones and evaporites interbedded with thin lacustrine or shallow marine shales and dolomites. The prolific petroleum systems that evolved within these series are associated with the Early Silurian and Late Devonian world-class source rocks and numerous Paleozoic and Triassic reservoirs. This regional review provides a renewed comprehensive insight into the geological evolution of the area that can help guide local exploration efforts, but also serves as a model for exploration in other intracratonic basins of the world.
- Published
- 2010
14. Contributors for Volumes 1A, 1B and 1C
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A.A. Antobreh, Olav Antonio Blaich, I.M. Artemieva, Peter Aukes, A.W. Bally, Y. Bartov, Z. Ben-Avraham, G.T. Bertram, T.G. Bevan, K.M. Bohacs, W. Borkowski, D. Bosence, William Bosworth, Robert Bourrouilh, T.A. Brent, D.S. Broad, David Brown, P.M. Burgess, T. Burke, E. Carminati, Joe Cartwright, O. Catuneanu, James A. Chalmers, F. Charlet, F.A. Cook, T. Cope, Branko Corner, J.A. Cupertino, J. Craig, L. Desheng, E. Deville, M. De Batist, P.W. Dickerson, C. Doglioni, T. Dooley, D. Druesne, C. Ebinger, Olav Eldholm, A-J. Everts, Jerome A. Eyer, Roberto Fainstein, J.D. Fairhead, Jan Inge Faleide, C.M.R. Fowler, D. Franke, U. Frieslander, S. Galeazzi, K. Gallagher, Z. Garfunkel, B. Gelabert, Richard G. Gibson, D. Gilbert, A. Ginzburg, S. Graham, S.A. Graham, N. Haddadi, Mohammad Hafid, J.C. Harrison, K. Hinz, L-Y. Hsiao, Philippe Huchon, Michael R. Hudec, R. Hus, Haddou Jabour, Martin P.A. Jackson, C.L. Johnson, E.H.A. Jungslager, M. Kennedy, A.C. Kerr, S.M. Khalil, O. Khlystov, J. Klerkx, M. Lazar, D.P. Le Heron, Keith Louden, L.P. Magnavita, G. Manatschal, M.A. Martins-Neto, A. Mascle, J. Mather, Ken McClay, I.R. McLachlan, Kristian E. Meisling, M.A. Menzies, Webster Ueipass Mohriak, A.R. Moustafa, W.R. Muehlberger, N. Destro, L. Naudts, J.E. Neal, Robert Newton, A.A. Nezhdanov, A. Nicolas, I.O. Norton, P.E. Olsen, G.F. Panza, J.A.M.M. Peijs, J.T. Piombino, S. Planke, O. Point, J. Poort, B.E. Prather, D. Procaccianti, R.B. Raykova, T.C. Redshaw, M. Reshef, B. Ritts, D.G. Roberts, E. Roca, D. Roeder, Y. Rotstein, M. Rottman, J. Roux, F. Sabat, D. Sawyer, W. Schlager, R.W. Schlische, D. Scrocca, H. Shulman, A. Sinkewich, C. Sladen, R.M. Slatt, R. Stephenson, Edgar Stettler, S. Stovba, O.E. Sutcliffe, Roger Swart, Johan C. Sydow, P. Szatmari, Anthony Tankard, Gabor Tari, Filippos Tsikalas, Brian E. Tucholke, Christopher I. Uruski, D. van der Spuy, A.J. van der Velden, J.-H. van Konijnenburg, A.V. Vyssotski, V.N. Vyssotski, A.B. Watts, P. Weimer, Herman Welsink, J. Wendebourg, R.S. White, P. Whitehouse, Robert B. Whitmarsh, R. Whittington, E.L. Winterer, M.O. Withjack, Lesli J. Wood, J.E. Wu, V. Zampetti, and Mahmoud Zizi
- Published
- 2012
15. The Illizi and Berkine Basins in Southern Algeria
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D. Druesne, S. Galeazzi, O. Point, N. Haddadi, and J. Mather
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Sedimentary depositional environment ,Paleontology ,Basement (geology) ,Paleozoic ,Source rock ,Evaporite ,Sedimentary rock ,Structural basin ,Unconformity ,Geology - Abstract
The Berkine and Illizi basins contain over 7000 meters of Palaeozoic and Mesozoic sedimentary rocks and numerous world-class petroleum systems with over 39 BBOE EUR reserves. Regional seismic and a well data are used to review its tectono-stratigraphic evolution. Sedimentary rocks are split into two first-order depositional supercycles: Gondwana and Tethys. These record extensional basin formation, followed by protracted periods of overall net subsidence, and conclude with basin inversion and regional uplift. Structural styles are dominated by recurrently reactivated transpressional and transtensional features strongly controlled by the basement structural grain, sitting within a long wave-length pattern of regional highs and lows. Depositional sequences are made up of laterally extensive coarse-grained fluvial and shallow marine reservoirs interbedded with widespread marine shales. 3 rd -order sequences display ramp-style to very low-angle sigmoidal stratal patterns. Unconformities are often structurally enhanced and record important and frequent breaks in sedimentation. Early Mesozoic evaporites interbedded with thin lacustrine and shallow marine deposits top-seal the petroleum systems, which are associated with Early Silurian and Late Devonian world-class source rocks and numerous Palaeozoic and Triassic reservoirs. This regional review provides a renewed comprehensive insight into the geological evolution of the area: a model for a world class petroleum province in an intracratonic setting.
- Published
- 2012
16. Algiers Pliocene Ria – A Messinian Canyon Filled by Gilbert Delta Complexes – A Preliminary Analyis
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N. Haddadi, J. L. Rubino, G. Clauzon, H. Naili, and O. Parize
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Delta ,Canyon ,geography ,Paleontology ,geography.geographical_feature_category ,Geology - Published
- 2005
17. Lower Palaeozoic Stratigraphic Cycles from South Western Algeria – Comparison between Ougarta Ranges, Timmoun and Illizi Basins
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N. Haddadi, J.L. Rubino, and S. Galeazzi
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Glaciology ,Paleontology ,Tectonics ,Stratigraphy ,Paleozoic ,Magmatism ,Ecological succession ,Structural basin ,Petrology ,Palaeogeography ,Geology - Abstract
B33 LOWER PALAEOZOIC STRATIGRAPHIC CYCLES FROM SOUTH WESTERN ALGERIA – COMPARISON BETWEEN OUGARTA RANGES TIMIMOUN AND ILLIZI BASINS 1 J.L. RUBINO 1 S. GALEAZZI 2 and N. HADDADI 3 1 Total CSTJF Pau France 2 Total UK Aberdeen UK 3 Total Paris France The last SGP 5 meeting held in Algeria in 2004 provides the opportunity to quickly analyse the lower Palaeozoic succession from Cambrian to Silurian in the Ougarta Ranges where it is well exposed. This succession can be first compare with coeval series developed in Subsurface in Timimoun basin and in turn with the classical succession known in
- Published
- 2005
18. Viscom: an orthogonal multiprocessor for early vision and neural computing
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K. Hwang, N. Haddadi, and Rama Chellappa
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Motion analysis ,Theoretical computer science ,Artificial neural network ,Computer science ,business.industry ,Optical flow ,Image processing ,Multiprocessing ,Application software ,computer.software_genre ,Convolution ,Computer engineering ,Concurrent computing ,Artificial intelligence ,business ,computer - Abstract
A categorization of important image/vision algorithms that can be efficiently implemented on a research multiprocessor called Viscom is presented. Extended C-language constructs are developed and used to specify orthogonal multiprocessing algorithms. Several early vision algorithms are illustrated, including convolution, optical flow, and 2D transforms. Motion analysis is modeled by an artificial neural network, which can also be efficiently mapped onto Viscom. Advantages of using Viscom for early vision and neural computing are discussed, and the associated hardware/software development experiences are reported. >
- Published
- 2002
19. A Comparison of Hidradenitis Suppurativa Characteristics Among Israeli Arabs and Jews: Analysis of Two Cohorts.
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Barak Levitt J, Barmatz S, Fisch-Gilad S, Taieb YH, Dalal A, Afshari K, Haddadi N, Tzur Bitan D, Dov Cohen A, Mimouni D, Hodak E, and Sherman S
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- Adult, Female, Humans, Male, Middle Aged, Cohort Studies, Comorbidity, Israel epidemiology, Prevalence, Retrospective Studies, Arabs statistics & numerical data, Hidradenitis Suppurativa ethnology, Hidradenitis Suppurativa epidemiology, Jews statistics & numerical data
- Abstract
Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease involving apocrine gland-bearing regions. There is an under-representation of non-Caucasians in epidemiologic studies of HS. The characteristics of HS in Israeli Arabs have not yet been studied., Objectives: To investigate the demographic and clinical profile of HS in the Israeli Arab population., Methods: A retrospective analysis was conducted in two cohorts of patients with HS in Israel. The patients were derived from the database of a large health management organization (n=4191, 639 Arabs; population-based) and a major tertiary medical center (n=372, 49 Arabs). Demographic and clinical data were compared between ethnic groups., Results: The prevalence of HS in Israeli Arabs was found to be 0.5%, fivefold higher than in Jews. Arab patients were younger (35.3 vs. 40.5 years, P < 0.001) and mostly male (52% vs. 35.7%, P < 0.001), with lower rates of co-morbidities, including smoking (40.8% vs. 55.7%, P < 0.001), hyperlipidemia, and depression as well as a higher rate of dissecting cellulitis (10.2% vs. 1.9%, P = 0.008). HS was more severe in Arabs, but of shorter duration, with mainly axillary involvement (79.6% vs. 57.9%, P = 0.004). Treatment with hormones was more common in Jews, and with biologic agents in Arabs., Conclusions: The findings suggest a different phenotype of HS in Arabs, warranting further study.
- Published
- 2024
20. Amantadine-induced hypersexuality in a non-Parkinsonian patient with catatonia: a case report.
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Gasnier M, Frajerman A, Haddadi N, Herrero H, Faulet T, Martin S, Korngold J, Colle R, Corruble E, and Choucha W
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- 2023
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21. Syringic acid Attenuates Oxidative Stress in Plasma and Peripheral Blood Mononuclear Cells of Patients with Acute Myeloid Leukemia.
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Haddadi N, Mirzania M, and Ansarihadipour H
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- Humans, Leukocytes, Mononuclear metabolism, Oxidative Stress, Catalase metabolism, Superoxide Dismutase metabolism, Glutathione Peroxidase metabolism, Lipid Peroxidation, Antioxidants pharmacology, Antioxidants metabolism, Leukemia, Myeloid, Acute drug therapy
- Abstract
Syringic acid (SA) is a natural phenolic acid that possesses antioxidant properties. The current study aimed to assess the possible ameliorative effects of SA on oxidative stress in patients with acute myeloid leukemia (AML). Twenty-two healthy donors as well as 22 sex- and age-matched AML patients participated in the study. AML patients were at the time of diagnosis and before remission. The peripheral blood mononuclear cells (PBMCs) and plasma samples were obtained and divided into four groups. The groups include: 1) buffer (B), containing isotonic phosphate buffer saline (100 mM, pH 7.4, 1 hr); 2) OX, containing solution subjected to iron-mediated oxidation (2.7 µM, 1 hr); 3) SA, containing SA solution (10 µM, 1 h) as ROS quencher and 4) SA + OX in which samples were pretreated with 10 µM of SA for 1 h, and then exposed to OX solution (2.7 µM) for 1 h. The results indicated that SA caused a significant increase in the activity of glutathione peroxidase (GPX) in PBMCs. Of note, the treatment of PBMCs and plasma samples of AML patients with SA was able to normalize the altered levels of GPX, superoxide dismutase (SOD), and catalase (CAT). The antioxidant effect of SA was further confirmed by analyzing the total oxidant status, lipid peroxidation, and protein carbonylation in both plasma samples and PBMCs of AML patients. According to the results, it seems that SA has strong protective effects on oxidative stress by elevating the total antioxidant status (TAS) of PBMCs and plasma specimens from AML patients.
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- 2023
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22. Expression Profile of Sphingosine Kinase 1 Isoforms in Human Cancer Tissues and Cells: Importance and Clinical Relevance of the Neglected 1b-Isoform.
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Chen H, Haddadi N, Zhu X, Hatoum D, Chen S, Nassif NT, Lin Y, and McGowan EM
- Abstract
Background: Overexpression of sphingosine kinase 1 (SphK1) is casually associated with many types of cancer, and inhibitors of SphK1 sensitize tumors to chemotherapy. SphK1 is expressed as two major isoforms, SphK1a and SphK1b. To date, no information has been reported on the SphK1 isoform expression profile and its clinical relevance., Objective: The objective is to examine the expression profile of the SphK1a and SPhK1b isoforms in human cancer and noncancer tissues and cell lines and explore their clinical relevance., Methods: We used PCR to qualitatively examine the expression profile of these two isoforms in breast, liver, and prostate cancer tissues plus paired adjacent tissues and in 11 cancer and normal cell lines (breast, cervical, bone, prostate, colon, brain, mesothelioma tumor and benign, and human kidney cells)., Results: We found that SphK1a was ubiquitously expressed in all cancer cells and tissues tested; in contrast, SphK1b was only expressed in selective cell types in breast, prostate, and lung cancer., Conclusions: Our data suggest that SphK1a is important for generic SphK1/S1P functions, and SphK1b mediates specialized and/or unique pathways in a specific type of tissue and could be a biomarker for cancer. This discovery is important for future SphK1-related cancer research and may have clinical implications in drug development associated with SphK1-directed cancer treatment., Competing Interests: The authors declare that they do not have conflicts of interest., (Copyright © 2022 Hongjie Chen et al.)
- Published
- 2022
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23. Studying the Oncosuppressive Functions of PTENP1 as a ceRNA.
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Travis G, Haddadi N, Simpson AM, Marsh DJ, McGowan EM, and Nassif NT
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- 3' Untranslated Regions genetics, Animals, Binding, Competitive, Cell Count, Cell Division, Cell Line, Tumor, Cloning, Molecular methods, Colorimetry methods, DNA Replication, Flow Cytometry methods, Fluorescent Dyes, Humans, Microscopy, Fluorescence, PTEN Phosphohydrolase genetics, Plasmids genetics, Staining and Labeling methods, Transfection methods, Tumor Suppressor Proteins genetics, Tumor Suppressor Proteins metabolism, MicroRNAs genetics, PTEN Phosphohydrolase metabolism, Pseudogenes genetics, Tumor Suppressor Proteins agonists
- Abstract
PTENP1 is a processed pseudogene of the tumour suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN). It functions posttranscriptionally to regulate PTEN by acting as a sponge for microRNAs that target PTEN. PTENP1 therefore functions as a competitive endogenous RNA (ceRNA), competing with PTEN for binding of microRNAs (miRNA) and thereby modulating PTEN cellular abundance. Studies of the overexpression of PTENP1 all confirm its oncosuppressive function to be mediated through the suppression of cell proliferation, induction of apoptosis, and inhibition of cell migration and invasion of cancer cells of differing types. These oncosuppressive functions are a direct consequence of miRNA binding by PTENP1 and the subsequent liberation of PTEN from miRNA induced suppression. In this chapter, we will focus initially on the description of a high efficiency transient transfection method to introduce and overexpress PTENP1 in the cell type of interest, followed by accurate methodologies to measure transfection efficiency by flow cytometry. We will then continue to describe two methods to analyze cell proliferation, namely the CCK-8 assay and Click-iT
® EdU assay. Due to commonalities in the manifestation of the oncosuppressive effects of PTENP1, mediated through its role as a ceRNA, the methods presented in this chapter will have wide applicability to a variety of different cell types.- Published
- 2021
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24. Targeting the SphK-S1P-SIPR Pathway as a Potential Therapeutic Approach for COVID-19.
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McGowan EM, Haddadi N, Nassif NT, and Lin Y
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- Betacoronavirus isolation & purification, COVID-19, Humans, Pandemics, SARS-CoV-2, Sphingosine metabolism, Betacoronavirus drug effects, Coronavirus Infections drug therapy, Lysophospholipids metabolism, Phosphotransferases (Alcohol Group Acceptor) antagonists & inhibitors, Pneumonia, Viral drug therapy, Sphingolipids pharmacology, Sphingosine analogs & derivatives, Sphingosine-1-Phosphate Receptors antagonists & inhibitors, Virus Replication drug effects
- Abstract
The world is currently experiencing the worst health pandemic since the Spanish flu in 1918-the COVID-19 pandemic-caused by the coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pandemic is the world's third wake-up call this century. In 2003 and 2012, the world experienced two major coronavirus outbreaks, SARS-CoV-1 and Middle East Respiratory syndrome coronavirus (MERS-CoV), causing major respiratory tract infections. At present, there is neither a vaccine nor a cure for COVID-19. The severe COVID-19 symptoms of hyperinflammation, catastrophic damage to the vascular endothelium, thrombotic complications, septic shock, brain damage, acute disseminated encephalomyelitis (ADEM), and acute neurological and psychiatric complications are unprecedented. Many COVID-19 deaths result from the aftermath of hyperinflammatory complications, also referred to as the "cytokine storm syndrome", endotheliitus and blood clotting, all with the potential to cause multiorgan dysfunction. The sphingolipid rheostat plays integral roles in viral replication, activation/modulation of the immune response, and importantly in maintaining vasculature integrity, with sphingosine 1 phosphate (S1P) and its cognate receptors (SIPRs: G-protein-coupled receptors) being key factors in vascular protection against endotheliitus. Hence, modulation of sphingosine kinase (SphK), S1P, and the S1P receptor pathway may provide significant beneficial effects towards counteracting the life-threatening, acute, and chronic complications associated with SARS-CoV-2 infection. This review provides a comprehensive overview of SARS-CoV-2 infection and disease, prospective vaccines, and current treatments. We then discuss the evidence supporting the targeting of SphK/S1P and S1P receptors in the repertoire of COVID-19 therapies to control viral replication and alleviate the known and emerging acute and chronic symptoms of COVID-19. Three clinical trials using FDA-approved sphingolipid-based drugs being repurposed and evaluated to help in alleviating COVID-19 symptoms are discussed.
- Published
- 2020
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25. Toward Systems Pathology for PTEN Diagnostics.
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Haddadi N, Travis G, Nassif NT, Simpson AM, and Marsh DJ
- Subjects
- Autism Spectrum Disorder genetics, Biomarkers, Tumor genetics, Genes, Tumor Suppressor, Genetic Testing, Germ-Line Mutation, Hamartoma Syndrome, Multiple genetics, Molecular Targeted Therapy methods, PTEN Phosphohydrolase metabolism, Phosphatidylinositol 3-Kinases, Neoplasms genetics, PTEN Phosphohydrolase genetics
- Abstract
Germline alterations of the tumor suppressor PTEN have been extensively characterized in patients with PTEN hamartoma tumor syndromes, encompassing subsets of Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus and Proteus-like syndromes, as well as autism spectrum disorder. Studies have shown an increase in the risk of developing specific cancer types in the presence of a germline PTEN mutation. Furthermore, outside of the familial setting, somatic variants of PTEN occur in numerous malignancies. Here we introduce and discuss the prospect of moving toward a systems pathology approach for PTEN diagnostics, incorporating clinical and molecular pathology data with the goal of improving the clinical management of patients with a PTEN mutation. Detection of a germline PTEN mutation can inform cancer surveillance and in the case of somatic mutation, have value in predicting disease course. Given that PTEN functions in the PI3K/AKT/mTOR pathway, identification of a PTEN mutation may highlight new therapeutic opportunities and/or inform therapeutic choices., (Copyright © 2020 Cold Spring Harbor Laboratory Press; all rights reserved.)
- Published
- 2020
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26. Treatment options for nonalcoholic fatty liver disease: a double-blinded randomized placebo-controlled trial.
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Anushiravani A, Haddadi N, Pourfarmanbar M, and Mohammadkarimi V
- Subjects
- Adolescent, Adult, Aged, Alanine Transaminase blood, Aspartate Aminotransferases blood, Biomarkers blood, Blood Glucose drug effects, Blood Glucose metabolism, Body Mass Index, Double-Blind Method, Female, Humans, Iran, Lipids blood, Male, Metformin adverse effects, Middle Aged, Non-alcoholic Fatty Liver Disease blood, Non-alcoholic Fatty Liver Disease diagnosis, Pioglitazone adverse effects, Risk Reduction Behavior, Silymarin adverse effects, Time Factors, Treatment Outcome, Vitamin E adverse effects, Waist Circumference, Young Adult, Metformin therapeutic use, Non-alcoholic Fatty Liver Disease drug therapy, Pioglitazone therapeutic use, Silymarin therapeutic use, Vitamin E therapeutic use
- Abstract
Introduction: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and is becoming the most frequent indication of liver transplantation. Cardiovascular disease is the main cause of death in these patients. There is no Food and Drug Association-approved medication for NAFLD patients. We aimed to provide more robust evidence on the use of medications that are inexpensive and available, namely, metformin, silymarin, pioglitazone, and vitamin E, for treating NAFLD., Materials and Methods: We conducted a randomized double-blinded, placebo-controlled trial on 150 consecutive patients with NAFLD who were assigned to five groups: lifestyle plus placebo, metformin 500 mg/day, silymarin 140 mg/day, pioglithasone 15 mg/day, and vitamin E 400 IU/day, all for 3 months. Anthropometric and biochemical variables were measured at baseline and 3 months later., Results: The mean age of the patients was 47.0±9.1 (range: 18-65) years and the sex distribution was 73 (48.7%) women and 77 (51.3%) men. Patients in all groups showed a significant improvement in anthropometric parameters such as waist circumference and BMI. There was no statistically significant difference in alanine transaminase and aspartate transaminase in the control group after treatment (P=0.51, 0.18, respectively); however, both liver enzymes decreased significantly in the other groups., Discussion and Conclusion: This randomized double-blinded placebo-controlled clinical trial suggested a significant benefit of silymarin, pioglitazone, and vitamin E in improving liver aminotransferases in patients with NAFLD after only 3 months, without exerting any specific side effects.
- Published
- 2019
- Full Text
- View/download PDF
27. PTEN/PTENP1: 'Regulating the regulator of RTK-dependent PI3K/Akt signalling', new targets for cancer therapy.
- Author
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Haddadi N, Lin Y, Travis G, Simpson AM, Nassif NT, and McGowan EM
- Subjects
- Animals, Antineoplastic Agents therapeutic use, Humans, MicroRNAs genetics, Neoplasms drug therapy, PTEN Phosphohydrolase genetics, Protein-Tyrosine Kinases genetics, Protein-Tyrosine Kinases metabolism, Signal Transduction drug effects, Signal Transduction genetics, Neoplasms metabolism, PTEN Phosphohydrolase metabolism, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt metabolism
- Abstract
Regulation of the PI-3 kinase (PI3K)/Akt signalling pathway is essential for maintaining the integrity of fundamental cellular processes, cell growth, survival, death and metabolism, and dysregulation of this pathway is implicated in the development and progression of cancers. Receptor tyrosine kinases (RTKs) are major upstream regulators of PI3K/Akt signalling. The phosphatase and tensin homologue (PTEN), a well characterised tumour suppressor, is a prime antagonist of PI3K and therefore a negative regulator of this pathway. Loss or inactivation of PTEN, which occurs in many tumour types, leads to overactivation of RTK/PI3K/Akt signalling driving tumourigenesis. Cellular PTEN levels are tightly regulated by a number of transcriptional, post-transcriptional and post-translational regulatory mechanisms. Of particular interest, transcription of the PTEN pseudogene, PTENP1, produces sense and antisense transcripts that exhibit post-transcriptional and transcriptional modulation of PTEN expression respectively. These additional levels of regulatory complexity governing PTEN expression add to the overall intricacies of the regulation of RTK/PI-3 K/Akt signalling. This review will discuss the regulation of oncogenic PI3K signalling by PTEN (the regulator) with a focus on the modulatory effects of the sense and antisense transcripts of PTENP1 on PTEN expression, and will further explore the potential for new therapeutic opportunities in cancer treatment.
- Published
- 2018
- Full Text
- View/download PDF
28. "Dicing and Splicing" Sphingosine Kinase and Relevance to Cancer.
- Author
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Haddadi N, Lin Y, Simpson AM, Nassif NT, and McGowan EM
- Subjects
- Animals, Disease Models, Animal, Evolution, Molecular, Humans, Isoenzymes, Lysophospholipids metabolism, Neoplasms drug therapy, Neoplasms pathology, Protein Transport, Receptors, Lysosphingolipid metabolism, Signal Transduction, Sphingosine analogs & derivatives, Sphingosine metabolism, Gene Expression Regulation, Neoplastic, Multigene Family, Neoplasms etiology, Neoplasms metabolism, Phosphotransferases (Alcohol Group Acceptor) genetics, Phosphotransferases (Alcohol Group Acceptor) metabolism, RNA Splicing
- Abstract
Sphingosine kinase (SphK) is a lipid enzyme that maintains cellular lipid homeostasis. Two SphK isozymes, SphK1 and SphK2, are expressed from different chromosomes and several variant isoforms are expressed from each of the isozymes, allowing for the multi-faceted biological diversity of SphK activity. Historically, SphK1 is mainly associated with oncogenicity, however in reality, both SphK1 and SphK2 isozymes possess oncogenic properties and are recognized therapeutic targets. The absence of mutations of SphK in various cancer types has led to the theory that cancer cells develop a dependency on SphK signaling (hyper-SphK signaling) or "non-oncogenic addiction". Here we discuss additional theories of SphK cellular mislocation and aberrant "dicing and splicing" as contributors to cancer cell biology and as key determinants of the success or failure of SphK/S1P (sphingosine 1 phosphate) based therapeutics., Competing Interests: The authors declare no conflict of interest.
- Published
- 2017
- Full Text
- View/download PDF
29. Mammalian sphingosine kinase (SphK) isoenzymes and isoform expression: challenges for SphK as an oncotarget.
- Author
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Hatoum D, Haddadi N, Lin Y, Nassif NT, and McGowan EM
- Subjects
- Animals, Biomarkers, Tumor, Cell Transformation, Neoplastic genetics, Cell Transformation, Neoplastic metabolism, Disease Susceptibility, Drug Discovery, Drug Resistance, Neoplasm genetics, Humans, Isoenzymes, Mice, Molecular Targeted Therapy, Multigene Family, Neoplasms drug therapy, Neoplasms genetics, Neoplasms metabolism, Neoplasms pathology, Phosphotransferases (Alcohol Group Acceptor) antagonists & inhibitors, Proprotein Convertases metabolism, Protein Binding, Receptors, Lysosphingolipid metabolism, Serine Endopeptidases metabolism, Gene Expression Regulation drug effects, Phosphotransferases (Alcohol Group Acceptor) genetics, Phosphotransferases (Alcohol Group Acceptor) metabolism
- Abstract
The various sphingosine kinase (SphK) isoenzymes (isozymes) and isoforms, key players in normal cellular physiology, are strongly implicated in cancer and other diseases. Mutations in SphKs, that may justify abnormal physiological function, have not been recorded. Nonetheless, there is a large and growing body of evidence demonstrating the contribution of gain or loss of function and the imbalance in the SphK/S1P rheostat to a plethora of pathological conditions including cancer, diabetes and inflammatory diseases. SphK is expressed as two isozymes SphK1 and SphK2, transcribed from genes located on different chromosomes and both isozymes catalyze the phosphorylation of sphingosine to S1P. Expression of each SphK isozyme produces alternately spliced isoforms. In recent years the importance of the contribution of SpK1 expression to treatment resistance in cancer has been highlighted and, additionally, differences in treatment outcome appear to also be dependent upon SphK isoform expression. This review focuses on an exciting emerging area of research involving SphKs functions, expression and subcellular localization, highlighting the complexity of targeting SphK in cancer and also comorbid diseases. This review also covers the SphK isoenzymes and isoforms from a historical perspective, from their first discovery in murine species and then in humans, their role(s) in normal cellular function and in disease processes, to advancement of SphK as an oncotarget.
- Published
- 2017
- Full Text
- View/download PDF
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