24 results on '"Shamma T"'
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2. Assessment of Closure’s Impact on Water Related Problems Around the Ononto Closure: An Integrated Approach for Solution
- Author
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Islam, M. A. R., Shamma, T. K., Anika, J. J., Hossain, M., di Prisco, Marco, Series Editor, Chen, Sheng-Hong, Series Editor, Vayas, Ioannis, Series Editor, Kumar Shukla, Sanjay, Series Editor, Sharma, Anuj, Series Editor, Kumar, Nagesh, Series Editor, Wang, Chien Ming, Series Editor, Arthur, Scott, editor, Saitoh, Masato, editor, and Pal, Sudip Kumar, editor
- Published
- 2022
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3. Assessment of Closure’s Impact on Water Related Problems Around the Ononto Closure: An Integrated Approach for Solution
- Author
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Islam, M. A. R., primary, Shamma, T. K., additional, Anika, J. J., additional, and Hossain, M., additional
- Published
- 2021
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4. Gulf Arabic Diacritization: Guidelines, Initial Dataset, and Results
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Alabbasi, Nouf, primary, Al-Badrashiny, Mohamed, additional, Aldahmani, Maryam, additional, AlDhanhani, Ahmed, additional, Alhashmi, Abdullah Saleh, additional, Alhashmi, Fawaghy Ahmed, additional, Al Hashemi, Khalid, additional, Alkhobbi, Rama Emad, additional, Al Maazmi, Shamma T, additional, Alyafeai, Mohammed Ali, additional, Alzaabi, Mariam M, additional, Alzaabi, Mohamed Saqer, additional, Badri, Fatma Khalid, additional, Darwish, Kareem, additional, Diab, Ehab Mansour, additional, Elmallah, Muhammad Morsy, additional, Elnashar, Amira Ayman, additional, Elneima, Ashraf Hatim, additional, Kabbani, MHD Tameem, additional, Rabih, Nour, additional, Saad, Ahmad, additional, and Sousou, Ammar Mamoun, additional
- Published
- 2022
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5. Productive Performance and some Blood Parameters of Broiler Chickens Fed Diets Supplemented with Thyme and Lavender Oils.
- Author
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Shamma, T., primary, El-Shafei, A., additional, and A. El-Yazby, W., additional
- Published
- 2019
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6. Dehydration of alcohols to ethers over Nafion-H, a solid perfluoroalkanesulfonic acid resin catalyst
- Author
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Olah, G.A., Shamma, T., and Prakash, G.K.S.
- Published
- 1997
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7. EFFECT OF OMEGA-3 SOURCES AND VITAMIN E SUPPLEMENTATION IN THE TURKEY TOMS DIET ON SEMEN CHARACTERISTICS AND FERTILIZING ABILITY.
- Author
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Shamma, T., primary, Meshreky, Samia, additional, Ibrahim, Samya, additional, and El-Aik, M., additional
- Published
- 2016
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8. LETTERS.
- Author
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ADAMS, H., DE LA POER BERESFORD, DONALD C., KANNANGARA, R. L., BERNHARDT, PAUL, SILVERMAN, RICA B., BEAUREGARD, ELIZABETH C., SHAMMA, T. M., MCDOWELL, DEAN N., REILAND, H. P., KOEHNE, CLYDE, ENZER, MILTON M., ROINSARD, P. M., WALKER, ROBERT R., KUSEL, ANITA DENTON, MALLARY, MARGOT, WRIGHT, JAMES N., HARTFORD, LORETTA, WYLER, WILLIAM, PÁEZ VILARÓ, MIGUEL, and WORTHY, J. F.
- Subjects
LAW enforcement - Published
- 1956
9. Association of Learning Style & Stress with Academic Achievement Among Physical Therapy Students
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Iqra Imtiaz, Mehar ul Nisa, Sobia Hina, Muhammad Junaid Khan, Suhail Karim, Naveed Ahmed, and Shamma Tabbasum
- Subjects
Vocational rehabilitation. Employment of people with disabilities ,HD7255-7256 ,Therapeutics. Psychotherapy ,RC475-489 - Abstract
Background: Learning styles are one of the different learning strategies used by students to enhance their academic performance. Medical education is linked with high stress among students There is little evidence regarding the association of stress and learning styles with the academic grades in Pakistan. Objective: To determine the association of learning styles and stress with academic performance, preferred learning style among final year Physical Therapy students and their level of stress. Methodology: A cross sectional study was conducted among 171 final year Physical Therapy students of Shifa Tameer-e-Millat University, Riphah international university, Rawalpindi medical college & Margalla institute of health sciences from 15 July to 15 December 2017. The population was selected using non-probability convenient sampling. Final year physical therapy students who were unmarried and with age ranging from 18-25 were included whereas students who were clinically diagnosed with depression and a learning disability including dyslexia were excluded. Standard questionnaire VARK (Visual, Aural, Read & Write & kinesthetic) was used to determine the preferred learning style and PSS (Perceived stress scale) was used to determine the level of stress among students. The results were analyzed using SPSS Version 21.0. Results: The preferred learning style among Physical Therapy students was Unimodal [54 out of 171(31.6%)] followed by Bimodal [53 out of 171 (31%)]. The statistical analysis showed no significant association between learning style and stress with academic performance (P>0.05). Conclusion: Preferred learning styles of Physical Therapy students were unimodal and bimodal, stress levels were moderate among students and there was no association between learning styles and stress with students’ academic performance. Keywords: Academic performance, Learning styles, Physical therapy, Stress, Students
- Published
- 2019
10. SEASONAL VARIATION AND PERFORMANCE EVALUATION OF BROILER BREEDER CHICKENS REARED IN ENCLOSED HOUSES.
- Author
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Abdel-Azeem, A. F., Shamma, T. A., and Omara, Y. O.
- Subjects
- *
SEASONAL physiological variations , *BROILER chickens , *CHICKENS , *POULTRY breeding , *PHYSIOLOGY - Abstract
In this field observational study three enclosed broiler breeder houses were selected to evaluate the effects of some environmental factors in different seasons along the year on F15 Hubbard broiler breeder chickens to provide reliable information and practical current knowledge for proper management conditions. Each house contains 4000 birds 25 Wk-old with average initial weight 2.560 ± 50.60 kg, with a total of 12000 birds for three studied houses. Productive performances of flocks were evaluated by measuring egg production, egg weight, feed consumption, feed conversion of eggs and mortality rate. Also, egg quality traits were done for each season alone, while the physiological performance determined by measuring some blood traits. Further, fertility, hatchability and chick quality traits were also evaluated. Ambient temperature (AT, °C), relative humidity (RH, %) and concentrations of ammonia (NH3, ppm), hydrogen sulfide (H2S, ppm), carbon dioxide (CO2, ppm) and dust (mg/m3), air velocity (AV, m/s) and static pressure (SP, Pa) were determined along the different seasons of the year. Results of the present study showed that air quality of breeder houses and either productive or physiological performance were significantly (P ≤ 0.05) affected due to seasonal changes along the year. High concentrations of different gases present in houses in winter season can negatively affect production and health of birds. In spring and summer seasons egg production and FCR were significantly (P ≤ 0.05) the best in comparison to the other different seasons. While, insignificant differences observed in egg weight due to seasonal changes. Mortality rate showed the highest percentage for birds reared in winter compared with the other seasons. In addition, there was evidence of an increased stress response due to elevation of environmental gases in winter and autumn seasons as judged by the increase of hetrophils, lymphocyte and H/L ratio and CS level reflecting the increase of stress due to environmental conditions. However, the levels of T3 and T4 recorded significantly higher (P ≤ 0.05) values for birds kept in winter season compared with the other seasons. Furthermore, egg quality traits had been significantly (P ≤ 0.05) affected due to seasonal changes, where the shell thickness recorded the highest (P ≤ 0.05) value during autumn and spring, while the lowest recorded for summer and winter seasons. Further, insignificant differences were detected for fertility, hatchability or chick quality traits due to seasonal changes. Based on the former results, it can be concluded that the tolerable temperature for the breeder was 19-28 °C, but decreasing AT to reach to 25 °C is required in summer season. Indeed, insufficient house environmental conditions were detected in winter season, which reduces the economic efficiency of enterprise due to lake of ventilation rate. However the quality of air in house is very important for obtaining good productive performance. Therefore, because of the difficult of achieving good environment in some housing types in different season, especially in winter, it is recommended that good care should be oriented to control of different gases generated in house in order to ensure good bird health and performance, when birds are most susceptible to harmful gases. In general an adequate environment within poultry houses is required for success in the poultry industry. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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11. Spermine inhibition of the 2,5-diaziridinyl-1,4-benzoquinone (DZQ) crosslinking reaction with DNA duplexes containing poly(purine){middle dot}poly(pyrimidine) tracts
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Shamma, T., primary and Haworth, I. S., additional
- Published
- 1999
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12. Convenient separation of high-purity C60 from crude fullerene extract by selective complexation with AlCl3.
- Author
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Bucsi, I., primary, Aniszfeld, R., additional, Shamma, T., additional, Prakash, G. K., additional, and Olah, G. A., additional
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- 1994
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13. Economical Efficiency of Poultry Projects for Chicken Meat Production.
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Anwar, A., Shamma, T. A., and Soliman, I.
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- 1977
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14. Spermine inhibition of the 2,5-diaziridinyl-1,4-benzoquinone (DZQ) crosslinking reaction with DNA duplexes containing poly(purine). poly(pyrimidine) tracts.
- Author
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Shamma, T and Haworth, I S
- Abstract
Upon reduction, 2,5-diaziridinyl-1,4-benzoquinone (DZQ) can form an interstrand guanine to guanine crosslink with DNA duplexes containing a d(GC).d(GC) dinucleotide step. The reaction is enhanced by a thymine positioned 5[prime] to each guanine [i.e. in a d(TGCA). d(TGCA) duplex fragment]. Here we show that spermine can inhibit DZQ crosslink formation in duplexes of sequence d[C(N6)TGCA(M6)C]. d[G(M[prime]6)TG-CA(N[prime]6)G]. For N6= M6= GGGGGG, N6= M6= a 'random' sequence and N6= GGGGGG and M6= a 'random' sequence, spermine concentrations of 20, 1 and 3 microM, respectively, were required for 50% inhibition of the DZQ crosslink. This suggests that spermine is more strongly bound to the polyguanosine tract than the random sequence, making it less available for crosslink inhibition. When the polyguanosine tract is interrupted by N 7-deazaguanine (D) located three bases, d(CGGGDGGTGCAGGDGGGC), and four bases, d(CG-GDGGGTGCAGGGDGGC), from the d(TGCA).d(TGCA) site, 30 and 3 microM spermine, respectively, were required for 50% crosslink inhibition. We suggest that this difference is due to the relative proximity of the three-guanosine tract to the d(TGCA).d(TGCA) site. We were able to confirm these conclusions with further experiments using duplexes containing three-guanosine and two-guanosine tracts and from computer simulations of the spermine-DNA complexes.
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- 1999
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15. Using Liver Organoids as Models to Study the Pathobiology of Rare Liver Diseases.
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Obeid DA, Mir TA, Alzhrani A, Altuhami A, Shamma T, Ahmed S, Kazmi S, Fujitsuka I, Ikhlaq M, Shabab M, Assiri AM, and Broering DC
- Abstract
Liver organoids take advantage of several important features of pluripotent stem cells that self-assemble in a three-dimensional culture matrix and reproduce many aspects of the complex organization found within their native tissue or organ counterparts. Compared to other 2D or 3D in vitro models, organoids are widely believed to be genetically stable or docile structures that can be programmed to virtually recapitulate certain biological, physiological, or pathophysiological features of original tissues or organs in vitro. Therefore, organoids can be exploited as effective substitutes or miniaturized models for the study of the developmental mechanisms of rare liver diseases, drug discovery, the accurate evaluation of personalized drug responses, and regenerative medicine applications. However, the bioengineering of organoids currently faces many groundbreaking challenges, including a need for a reasonable tissue size, structured organization, vascularization, functional maturity, and reproducibility. In this review, we outlined basic methodologies and supplements to establish organoids and summarized recent technological advances for experimental liver biology. Finally, we discussed the therapeutic applications and current limitations.
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- 2024
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16. Whole Liver Derived Acellular Extracellular Matrix for Bioengineering of Liver Constructs: An Updated Review.
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Mir TA, Alzhrani A, Nakamura M, Iwanaga S, Wani SI, Altuhami A, Kazmi S, Arai K, Shamma T, Obeid DA, Assiri AM, and Broering DC
- Abstract
Biomaterial templates play a critical role in establishing and bioinstructing three-dimensional cellular growth, proliferation and spatial morphogenetic processes that culminate in the development of physiologically relevant in vitro liver models. Various natural and synthetic polymeric biomaterials are currently available to construct biomimetic cell culture environments to investigate hepatic cell-matrix interactions, drug response assessment, toxicity, and disease mechanisms. One specific class of natural biomaterials consists of the decellularized liver extracellular matrix (dECM) derived from xenogeneic or allogeneic sources, which is rich in bioconstituents essential for the ultrastructural stability, function, repair, and regeneration of tissues/organs. Considering the significance of the key design blueprints of organ-specific acellular substrates for physiologically active graft reconstruction, herein we showcased the latest updates in the field of liver decellularization-recellularization technologies. Overall, this review highlights the potential of acellular matrix as a promising biomaterial in light of recent advances in the preparation of liver-specific whole organ scaffolds. The review concludes with a discussion of the challenges and future prospects of liver-specific decellularized materials in the direction of translational research.
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- 2023
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17. Therapeutic nexus of T cell immunometabolism in improving transplantation immunotherapy.
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Kazmi S, Khan MA, Shamma T, Altuhami A, Assiri AM, and Broering DC
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- Cell Differentiation, Lymphocyte Activation, Signal Transduction, Immunotherapy, T-Lymphocytes, Regulatory
- Abstract
Immunometabolism is a therapeutic strategy to tune immune cells through metabolic reprogramming, which allows immune cells to be differentiated according to their energy requirements. Recent therapeutic strategies targeting immunometabolism suggest that intracellular metabolic reprogramming controls T cell activation, proliferation, and differentiation into effector (Teff) or regulatory (Treg) cells. Immunometabolism is being studied for the treatment of inflammatory diseases, including those associated with solid organ transplantation (SOT). Here, we review immunometabolic regulation of immune cells, with a particular focus on Treg metabolic regulation and liver kinase B1 (LKB1) signaling, which stabilize Tregs and prevent inflammation-associated tissue injuries. All in all, here we discussed how targeting T cell immunometabolism modulates Teff and Treg-mediated immune responses, which can be used to boost Treg differentiation, stability, and ultimately favor immunotolerance in clinical transplants., (Copyright © 2022 Elsevier B.V. All rights reserved.)
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- 2022
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18. CTLA4-Ig mediated immunosuppression favors immunotolerance and restores graft in mouse airway transplants.
- Author
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Khan MA, Shamma T, Altuhami A, Ahmed HA, Assiri AM, and Broering DC
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- Abatacept pharmacology, Abatacept therapeutic use, Animals, Fibrosis, Forkhead Transcription Factors, Immunosuppression Therapy, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, T-Lymphocytes, Regulatory immunology, Trachea transplantation, CTLA-4 Antigen administration & dosage, CTLA-4 Antigen immunology, Graft Rejection immunology, Graft Rejection prevention & control, Graft Survival immunology
- Abstract
CTLA4-Ig is a potent costimulatory blocker that inhibits T cell activation during alloimmune inflammation and increases graft survival and function. CTLA4-Ig-mediated immunosuppression has been demonstrated to support transplant function in various clinical trials and preclinical settings, but its effects on the balance between regulatory T cells (Tregs) and effector T cells (Teffs), as well as complement activation, are less well investigated. In the present study, we proposed to investigate the effects of CTLA4-Ig mediated immunosuppression on the phase of immunotolerance and the subsequent graft microvascular and epithelial repair during the progression of subepithelial fibrosis in a mouse model of orthotopic trachea transplantation. Briefly, CTLA4-Ig treated allografts (2 mg/kg, I.P.), untreated allografts, and syngrafts were serially monitored for peripheral FOXP3
+ Tregs, antibody-mediated complement activation (C3d and C4d), tissue oxygenation, donor-recipient microvascular blood flow, and subsequent tissue remodeling following transplantation. Our data demonstrate that CTLA4-Ig mediated immunosuppression significantly results in late increases in both peripheral CD4+ /CD8+ FOXP3+ Tregs and serum IL-10, but prevents the microvascular deposition of IgG, complement factor C3d, and epithelial C4d respectively, which proportionally improved blood flow and tissue oxygenation in the graft and, thus, promotes graft repair. Also, it restored the airway lumen, epithelium, and prevented the progression of subepithelial collagen deposition up to 90 days after transplantation. This study demonstrates that CTLA4-Ig-mediated immunosuppression potentially modulates both effector response and a late surge of regulatory activity to preserve graft microvasculature and rescue allograft from sustained hypoxia and ischemia and thereby limits subepithelial fibrosis., (Copyright © 2022. Published by Elsevier Ltd.)- Published
- 2022
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19. Targeting Interleukin-10 Restores Graft Microvascular Supply and Airway Epithelium in Rejecting Allografts.
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Kazmi S, Khan MA, Shamma T, Altuhami A, Ahmed HA, Mohammed Assiri A, and Broering DC
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- Animals, Endothelial Cells immunology, Epithelial Cells immunology, Epithelium immunology, Graft Survival physiology, Immune Tolerance, Immunosuppression Therapy, Interleukin-10 physiology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Microvessels immunology, Microvessels physiology, T-Lymphocytes, Regulatory immunology, Transplantation, Homologous methods, Allografts metabolism, Graft Rejection immunology, Interleukin-10 metabolism
- Abstract
Interleukin-10 (IL-10) is a vital regulatory cytokine, which plays a constructive role in maintaining immune tolerance during an alloimmune inflammation. Our previous study highlighted that IL-10 mediated immunosuppression established the immune tolerance phase and thereby modulated both microvascular and epithelial integrity, which affected inflammation-associated graft malfunctioning and sub-epithelial fibrosis in rejecting allografts. Here, we further investigated the reparative effects of IL-10 on microvasculature and epithelium in a mouse model of airway transplantation. To investigate the IL-10 mediated microvascular and epithelial repair, we depleted and reconstituted IL-10, and monitored graft microvasculature, airway epithelium, and associated repair proteins. Our data demonstrated that both untreated control allografts and IL-10 (-) allografts showed a significant early (d6) increase in microvascular leakiness, drop-in tissue oxygenation, blood perfusion, and denuded airway epithelium, which is associated with loss of adhesion protein Fascin-1 and β-catenin on vascular endothelial cells at d10 post-transplantation. However, IL-10 (+) promotes early microvascular and airway epithelial repair, and a proportional increase in endothelial Fascin-1, and β-catenin at d10 post-transplantation. Moreover, airway epithelial cells also express a significantly higher expression of FOXJ1 and β-catenin in syngrafts and IL-10 (+) allografts as compared to IL-10 (-) and untreated controls at d10 post-transplantation. Collectively, these findings demonstrated that IL-10 mediated microvascular and epithelial changes are associated with the expression of FOXJ1, β-catenin, and Fascin-1 proteins on the airway epithelial and vascular endothelial cells, respectively. These findings establish a potential reparative modulation of IL-10 associated microvascular and epithelial repair, which could provide a vital therapeutic strategy to facilitate graft repair in clinical settings.
- Published
- 2022
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20. IL-10 Mediated Immunomodulation Limits Subepithelial Fibrosis and Repairs Airway Epithelium in Rejecting Airway Allografts.
- Author
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Khan MA, Ashoor GA, Shamma T, Alanazi F, Altuhami A, Kazmi S, Ahmed HA, Mohammed Assiri A, and Clemens Broering D
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- Animals, Disease Models, Animal, Fibrosis, Graft Rejection immunology, Graft Rejection pathology, Graft Survival, Inflammation Mediators metabolism, Interleukin-10 genetics, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Respiratory Mucosa immunology, Respiratory Mucosa pathology, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory metabolism, Time Factors, Trachea immunology, Trachea metabolism, Trachea pathology, Transplantation Tolerance, Mice, Graft Rejection metabolism, Interleukin-10 metabolism, Re-Epithelialization, Respiratory Mucosa metabolism, Trachea transplantation
- Abstract
Interleukin-10 plays a vital role in maintaining peripheral immunotolerance and favors a regulatory immune milieu through the suppression of T effector cells. Inflammation-induced microvascular loss has been associated with airway epithelial injury, which is a key pathological source of graft malfunctioning and subepithelial fibrosis in rejecting allografts. The regulatory immune phase maneuvers alloimmune inflammation through various regulatory modulators, and thereby promotes graft microvascular repair and suppresses the progression of fibrosis after transplantation. The present study was designed to investigate the therapeutic impact of IL-10 on immunotolerance, in particular, the reparative microenvironment, which negates airway epithelial injury, and fibrosis in a mouse model of airway graft rejection. Here, we depleted and reconstituted IL-10, and serially monitored the phase of immunotolerance, graft microvasculature, inflammatory cytokines, airway epithelium, and subepithelial collagen in rejecting airway transplants. We demonstrated that the IL-10 depletion suppresses FOXP3
+ Tregs, tumor necrosis factor-inducible gene 6 protein (TSG-6), graft microvasculature, and establishes a pro-inflammatory phase, which augments airway epithelial injury and subepithelial collagen deposition while the IL-10 reconstitution facilitates FOXP3+ Tregs, TSG-6 deposition, graft microvasculature, and thereby favors airway epithelial repair and subepithelial collagen suppression. These findings establish a potential reparative modulation of IL-10-associated immunotolerance on microvascular, epithelial, and fibrotic remodeling, which could provide a vital therapeutic option to rescue rejecting transplants in clinical settings.- Published
- 2021
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21. Hypoxia-induced complement dysregulation is associated with microvascular impairments in mouse tracheal transplants.
- Author
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Khan MA, Shamma T, Kazmi S, Altuhami A, Ahmed HA, Assiri AM, and Broering DC
- Subjects
- Animals, Hypoxia, Mice, Mice, Inbred C57BL, Trachea, Endothelial Cells, Graft Rejection
- Abstract
Background: Complement Regulatory Proteins (CRPs), especially CD55 primarily negate complement factor 3-mediated injuries and maintain tissue homeostasis during complement cascade activation. Complement activation and regulation during alloimmune inflammation contribute to allograft injury and therefore we proposed to investigate a crucial pathological link between vascular expression of CD55, active-C3, T cell immunity and associated microvascular tissue injuries during allograft rejection., Methods: Balb/c→C57BL/6 allografts were examined for microvascular deposition of CD55, C3d, T cells, and associated tissue microvascular impairments during rejection in mouse orthotopic tracheal transplantation., Results: Our findings demonstrated that hypoxia-induced early activation of HIF-1α favors a cell-mediated inflammation (CD4
+ , CD8+ , and associated proinflammatory cytokines, IL-2 and TNF-α), which proportionally triggers the downregulation of CRP-CD55, and thereby augments the uncontrolled release of active-C3, and Caspase-3 deposition on CD31+ graft vascular endothelial cells. These molecular changes are pathologically associated with microvascular deterioration (low tissue O2 and Blood flow) and subsequent airway epithelial injuries of rejecting allografts as compared to non-rejecting syngrafts., Conclusion: Together, these findings establish a pathological correlation between complement dysregulation, T cell immunity, and microvascular associated injuries during alloimmune inflammation in transplantation.- Published
- 2020
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22. iPSC-derived MSC therapy induces immune tolerance and supports long-term graft survival in mouse orthotopic tracheal transplants.
- Author
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Khan MA, Alanazi F, Ahmed HA, Shamma T, Kelly K, Hammad MA, Alawad AO, Assiri AM, and Broering DC
- Subjects
- Animals, Cells, Cultured, Graft Rejection immunology, Induced Pluripotent Stem Cells cytology, Induced Pluripotent Stem Cells immunology, Mesenchymal Stem Cells cytology, Mesenchymal Stem Cells immunology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Organ Transplantation adverse effects, T-Lymphocytes, Regulatory immunology, Graft Rejection therapy, Graft Survival, Mesenchymal Stem Cell Transplantation methods, Organ Transplantation methods, Trachea transplantation, Transplantation Tolerance
- Abstract
Background: Lung transplantation is a life-saving surgical replacement of diseased lungs in patients with end-stage respiratory malfunctions. Despite remarkable short-term recovery, long-term lung survival continues to face several major challenges, including chronic rejection and severe toxic side effects due to global immunosuppression. Stem cell-based immunotherapy has been recognized as a crucial immunoregulatory regimen in various preclinical and clinical studies. Despite initial therapeutic outcomes, conventional stem cells face key limitations. The novel Cymerus™ manufacturing facilitates production of a virtually limitless supply of consistent human induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells, which could play a key role in selective immunosuppression and graft repair during rejection., Methods: Here, we demonstrated the impact of iPSC-derived human MSCs on the development of immune tolerance and long-term graft survival in mouse orthotopic airway allografts. BALB/c → C57BL/6 allografts were reconstituted with iPSC-derived MSCs (2 million/transplant/at d0), and allografts were examined for regulatory T cells (Tregs), oxygenation, microvascular blood flow, airway epithelium, and collagen deposition during rejection., Results: We demonstrated that iPSC-derived MSC treatment leads to significant increases in hTSG-6 protein, followed by an upregulation of mouse Tregs and IL-5, IL-10, and IL-15 cytokines, which augments graft microvascular blood flow and oxygenation, and thereby maintained a healthy airway epithelium and prevented the subepithelial deposition of collagen at d90 post transplantation., Conclusions: Collectively, these data confirmed that iPSC-derived MSC-mediated immunosuppression has potential to establish immune tolerance and rescue allograft from sustained hypoxic/ischemic phase, and subsequently limits long-term airway epithelial injury and collagen progression, which therapeutically warrant a study of Cymerus iPSC-derived MSCs as a potential management option for immunosuppression in transplant recipients.
- Published
- 2019
- Full Text
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23. Complement factor and T-cell interactions during alloimmune inflammation in transplantation.
- Author
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Khan MA and Shamma T
- Subjects
- Animals, Humans, Lymphocyte Activation immunology, T-Lymphocytes immunology, Cell Communication, Complement System Proteins metabolism, Inflammation immunology, Inflammation pathology, T-Lymphocytes cytology, Transplantation
- Abstract
Complement factor and T-cell signaling during an effective alloimmune response plays a key role in transplant-associated injury, which leads to the progression of chronic rejection (CR). During an alloimmune response, activated complement factors (C3a and C5a) bind to their corresponding receptors (C3aR and C5aR) on a number of lymphocytes, including T-regulatory cells (Tregs), and these cell-molecular interactions have been vital to modulate an effective immune response to/from Th1-effector cell and Treg activities, which result in massive inflammation, microvascular impairments, and fibrotic remodeling. Involvement of the complement-mediated cell signaling during transplantation signifies a crucial role of complement components as a key therapeutic switch to regulate ongoing inflammatory state, and further to avoid the progression of CR of the transplanted organ. This review highlights the role of complement-T cell interactions, and how these interactions shunt the effector immune response during alloimmune inflammation in transplantation, which could be a novel therapeutic tool to protect a transplanted organ and avoid progression of CR., (©2018 Society for Leukocyte Biology.)
- Published
- 2019
- Full Text
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24. Mutagenicity studies of methyl-tert-butylether using the Ames tester strain TA102.
- Author
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Williams-Hill D, Spears CP, Prakash S, Olah GA, Shamma T, Moin T, Kim LY, and Hill CK
- Subjects
- Aldehyde Oxidoreductases metabolism, Animals, DNA, Bacterial drug effects, Dose-Response Relationship, Drug, Genes, Bacterial drug effects, Humans, Microsomes, Liver metabolism, Mutagenicity Tests, Rats, Salmonella typhimurium classification, Salmonella typhimurium genetics, Air Pollutants toxicity, Carcinogens toxicity, Methyl Ethers toxicity, Mutagens toxicity, Salmonella typhimurium drug effects
- Abstract
Methyl-tert-butylether (MTBE) is an oxygenate widely used in the United States as a motor vehicle fuel additive to reduce emissions and as an octane booster [National Research Council, Toxicological and Performance Aspects of Oxygenated Motor Vehicle Fules, National Academy Press, Washington, DC, 1996]. But it is the potential for MTBE to enter drinking water supplies that has become an area of public concern. MTBE has been shown to induce liver and kidney tumors in rodents but the biochemical process leading to carcinogenesis is unknown. MTBE was previously shown to be non-mutagenic in the standard Ames plate incorporation test with tester strains that detect frame shift (TA98) and point mutations (TA100) and in a suspension assay using TA104, a strain that detects oxidative damage, suggesting a non-genotoxic mechanism accounts for its carcinogenic potential. These strains are deficient in excision repair due to deletion of the uvrB gene. We hypothesized that the carcinogenic activity of MTBE may be dependent upon a functional excision repair system that attempts to remove alkyl adducts and/or oxidative base damage caused by direct interaction of MTBE with DNA or by its metabolites, formaldehyde and tert-butyl alcohol (TBA), established carcinogens that are mutagenic in some Ames strains. To test our hypothesis, the genotoxicity of MTBE-induced DNA alterations was assayed using the standard Ames test with TA102, a strain similar to TA104 in the damage it detects but uvrB + and, therefore, excision repair proficient. The assay was performed (1) with and without Aroclor-induced rat S-9, (2) with and without the addition of formaldehyde dehydrogenase (FDH), and (3) with human S-9 homogenate. MTBE was weakly mutagenic when tested directly and moderately mutagenic with S-9 activation producing between 80 and 200 TA102 revertants/mg of compound. Mutagenicity was inhibited 25%-30% by FDH. TA102 revertants were also induced by TBA and by MTBE when human S-9 was substituted for rat S-9. We conclude that MTBE and its metabolites induce a mutagenic pathway involving oxidation of DNA bases and an intact repair system. These data are significant in view of the controversy surrounding public safety and the environmental release of MTBE and similar fuel additives.
- Published
- 1999
- Full Text
- View/download PDF
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