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869 results on '"Al-Abed, Yousef"'

7. β2-spectrin (SPTBN1) as a therapeutic target for diet-induced liver disease and preventing cancer development.

Author

Rao, Shuyun, Yang, Xiaochun, Ohshiro, Kazufumi, Zaidi, Sobia, Wang, Zhanhuai, Shetty, Kirti, Xiang, Xiyan, Hassan, Md, Mohammad, Taj, Latham, Patricia, Nguyen, Bao-Ngoc, Wong, Linda, Yu, Herbert, Al-Abed, Yousef, Mishra, Bibhuti, Vacca, Michele, Guenigault, Gareth, Allison, Michael, Vidal-Puig, Antonio, Benhammou, Jihane, Alvarez, Marcus, Pajukanta, Päivi, Pisegna, Joseph, and Mishra, Lopa

Subjects
Animals, Diet, High-Fat, Liver, Mice, Mice, Inbred C57BL, Neoplasms, Non-alcoholic Fatty Liver Disease, Spectrin
Abstract

The prevalence of nonalcoholic steatohepatitis (NASH) and liver cancer is increasing. De novo lipogenesis and fibrosis contribute to disease progression and cancerous transformation. Here, we found that β2-spectrin (SPTBN1) promotes sterol regulatory element (SRE)–binding protein (SREBP)–stimulated lipogenesis and development of liver cancer in mice fed a high-fat diet (HFD) or a western diet (WD). Either hepatocyte-specific knockout of SPTBN1 or siRNA-mediated therapy protected mice from HFD/WD-induced obesity and fibrosis, lipid accumulation, and tissue damage in the liver. Biochemical analysis suggested that HFD/WD induces SPTBN1 and SREBP1 cleavage by CASPASE-3 and that the cleaved products interact to promote expression of genes with sterol response elements. Analysis of human NASH tissue revealed increased SPTBN1 and CASPASE-3 expression. Thus, our data indicate that SPTBN1 represents a potential target for therapeutic intervention in NASH and liver cancer.

Published
2021

10. Thiocarbazate building blocks enable the construction of azapeptides for rapid development of therapeutic candidates

Author

Altiti, Ahmad, He, Mingzhu, VanPatten, Sonya, Cheng, Kai Fan, Ahmed, Umair, Chiu, Pui Yan, Mughrabi, Ibrahim T., Jabari, Bayan Al, Burch, Ronald M., Manogue, Kirk R., Tracey, Kevin J., Diamond, Betty, Metz, Christine N., Yang, Huan, Hudson, LaQueta K., Zanos, Stavros, Son, Myoungsun, Sherry, Barbara, Coleman, Thomas R., and Al-Abed, Yousef

Published
2022
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12. HMGB1-mediated restriction of EPO signaling contributes to anemia of inflammation

Author

Dulmovits, Brian M., Tang, Yuefeng, Papoin, Julien, He, Mingzhu, Li, Jianhua, Yang, Huan, Addorisio, Meghan E., Kennedy, Lauren, Khan, Mushran, Brindley, Elena, Ashley, Ryan J., Ackert-Bicknell, Cheryl, Hale, John, Kurita, Ryo, Nakamura, Yukio, Diamond, Betty, Barnes, Betsy J., Hermine, Olivier, Gallagher, Patrick G., Steiner, Laurie A., Lipton, Jeffrey M., Taylor, Naomi, Mohandas, Narla, Andersson, Ulf, Al-Abed, Yousef, Tracey, Kevin J., and Blanc, Lionel

Published
2022
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14. Exploring Lysophosphatidylcholine as a Biomarker in Ischemic Stroke: The Plasma–Brain Disjunction.

Author

Turpin, Justin, Wadolowski, Steven, Tambo, Willians, Kim, Daniel, Al Abed, Yousef, Sciubba, Daniel M., Becker, Lance B., Ledoux, David, Kim, Junhwan, Powell, Keren, and Li, Chunyan

Subjects
ISCHEMIC stroke, LABORATORY rats, ARTERIAL occlusions, CEREBRAL arteries, PROGNOSIS
Abstract

Lipids and their bioactive metabolites, notably lysophosphatidylcholine (LPC), are increasingly important in ischemic stroke research. Reduced plasma LPC levels have been linked to stroke occurrence and poor outcomes, positioning LPC as a potential prognostic or diagnostic marker. Nonetheless, the connection between plasma LPC levels and stroke severity remains unclear. This study aimed to elucidate this relationship by examining plasma LPC levels in conjunction with brain LPC levels to provide a deeper understanding of the underlying mechanisms. Adult male Sprague–Dawley rats underwent transient middle cerebral artery occlusion and were randomly assigned to different groups (sham-operated, vehicle, LPC supplementation, or LPC inhibition). We measured multiple LPC species in the plasma and brain, alongside assessing sensorimotor dysfunction, cerebral perfusion, lesion volume, and markers of BBB damage, inflammation, apoptosis, and oxidative stress. Among five LPC species, plasma LPC(16:0) and LPC(18:1) showed strong correlations with sensorimotor dysfunction, lesion severity, and mechanistic biomarkers in the rat stroke model. Despite notable discrepancies between plasma and brain LPC levels, both were strongly linked to functional outcomes and mechanistic biomarkers, suggesting that LPC's prognostic value is retained extracranially. This study advances the understanding of LPC as a blood marker in ischemic stroke and highlights directions for future research to further elucidate its association with stroke severity, particularly through investigations in more clinically representative models. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Adenylyl Cyclase 6 Mediates Inhibition of TNF in the Inflammatory Reflex

Author

Tarnawski, Laura, Reardon, Colin, Caravaca, April S, Rosas-Ballina, Mauricio, Tusche, Michael W, Drake, Anna R, Hudson, LaQueta K, Hanes, William M, Li, Jian Hua, Parrish, William R, Ojamaa, Kaie, Al-Abed, Yousef, Faltys, Michael, Pavlov, Valentin A, Andersson, Ulf, Chavan, Sangeeta S, Levine, Yaakov A, Mak, Tak W, Tracey, Kevin J, and Olofsson, Peder S

Subjects
Biomedical and Clinical Sciences, Neurosciences, 1.1 Normal biological development and functioning, Underpinning research, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Adenylyl Cyclases, Animals, CREB-Binding Protein, Cell Line, Endotoxins, Inflammation, Macrophages, Male, Mice, Mice, Inbred C57BL, RAW 264.7 Cells, Rats, Rats, Sprague-Dawley, Reflex, Spleen, Tumor Necrosis Factors, Vagus Nerve, alpha7 Nicotinic Acetylcholine Receptor, inflammatory reflex, choline acetyltransferase, acetylcholine, adenylyl cyclase 6, sustained TNF inhibition, vagus nerve stimulation/VNS, alpha 7nAChR, α7nAChR, Immunology, Medical Microbiology, Biochemistry and cell biology, Genetics
Abstract

Macrophage cytokine production is regulated by neural signals, for example in the inflammatory reflex. Signals in the vagus and splenic nerves are relayed by choline acetyltransferase+ T cells that release acetylcholine, the cognate ligand for alpha7 nicotinic acetylcholine subunit-containing receptors (α7nAChR), and suppress TNF release in macrophages. Here, we observed that electrical vagus nerve stimulation with a duration of 0.1-60 s significantly reduced systemic TNF release in experimental endotoxemia. This suppression of TNF was sustained for more than 24 h, but abolished in mice deficient in the α7nAChR subunit. Exposure of primary human macrophages and murine RAW 264.7 macrophage-like cells to selective ligands for α7nAChR for 1 h in vitro attenuated TNF production for up to 24 h in response to endotoxin. Pharmacological inhibition of adenylyl cyclase (AC) and knockdown of adenylyl cyclase 6 (AC6) or c-FOS abolished cholinergic suppression of endotoxin-induced TNF release. These findings indicate that action potentials in the inflammatory reflex trigger a change in macrophage behavior that requires AC and phosphorylation of the cAMP response element binding protein (CREB). These observations further our mechanistic understanding of neural regulation of inflammation and may have implications for development of bioelectronic medicine treatment of inflammatory diseases.

Published
2018

16. Ultrasound Neuromodulation of an Anti-Inflammatory Pathway at the Spleen Improves Experimental Pulmonary Hypertension

Author

Zafeiropoulos, Stefanos, primary, Ahmed, Umair, additional, Bekiaridou, Alexandra, additional, Jayaprakash, Naveen, additional, Mughrabi, Ibrahim T., additional, Saleknezhad, Nafiseh, additional, Chadwick, Chrystal, additional, Daytz, Anna, additional, Kurata-Sato, Izumi, additional, Atish-Fregoso, Yemil, additional, Carroll, Kaitlin, additional, Al-Abed, Yousef, additional, Fudim, Marat, additional, Puleo, Christopher, additional, Giannakoulas, George, additional, Nicolls, Mark, additional, Diamond, Betty, additional, and Zanos, Stavros, additional

Published
2024
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20. Effects of novel muscarinic M3 receptor ligand C1213 in pulmonary arterial hypertension models.

Author

Ahmed, Mohamed, VanPatten, Sonya, Lakshminrusimha, Satyanarayana, Patel, Hardik, Coleman, Thomas, and Al-Abed, Yousef

Subjects
PPHN, C1213, muscarinic receptor, nitric oxide, pulmonary hypertension, Animals, Antihypertensive Agents, Benzylamines, Blood Pressure, Cell Hypoxia, Cell Line, Disease Models, Animal, Endothelial Cells, Guanidines, Humans, Hypertension, Pulmonary, Nitric Oxide Synthase Type III, Oncogene Protein v-akt, Pulmonary Artery, Receptor, Muscarinic M3, Sheep, Signal Transduction
Abstract

Pulmonary hypertension (PH) is a complex disease comprising a pathologic remodeling and thickening of the pulmonary vessels causing an after load on the right heart ventricle that can result in ventricular failure. Triggered by oxidative stress, episodes of hypoxia, and other undetermined causes, PH is associated with poor outcomes and a high rate of morbidity. In the neonate, this disease has a similar etiology but is further complicated by the transition to breathing after birth, which requires a reduction in vascular resistance. Persistent pulmonary hypertension of the newborn (PPHN) is one form of PH that is frequently unresponsive to current therapies including inhaled nitric oxide (due to lack of proper absorption and diffusion), and other therapeutics targeting signaling mediators in vascular endothelium and smooth muscle. The need for novel agents, which target distinct pathways in pulmonary hypertension, remains. Herein, we investigated the therapeutic effects of novel muscarinic receptor ligand C1213 in models of PH We demonstrated that via M3 muscarinic receptors, C1213 induced activating- eNOS phosphorylation (serine-1177), which is known to lead to nitric oxide (NO) production in endothelial cells. Using signaling pathway inhibitors, we discovered that AKT and calcium signaling contributed to eNOS phosphorylation induced by C1213. As expected for an eNOS-stimulating agent, in ex vivo and in vivo models, C1213 triggered pulmonary vasodilation and induced both pulmonary artery and systemic blood pressure reductions demonstrating its potential value in PH and PPHN In brief, this proof-of-concept study provides evidence that an M3 muscarinic receptor functionally selective ligand stimulates downstream pathways leading to antihypertensive effects using in vitro, ex vivo, and in vivo models of PH.

Published
2016

23. Inhibition of IRF5 hyperactivation protects from lupus onset and severity

Author

Song, Su, De, Saurav, Nelson, Victoria, Chopra, Samin, LaPan, Margaret, Kampta, Kyle, Sun, Shan, He, Mingzhu, Thompson, Cherrie D., Li, Dan, Shih, Tiffany, Tan, Natalie, Al-Abed, Yousef, Capitle, Eugenio, Aranow, Cynthia, Mackay, Meggan, Clapp, William L., and Barnes, Betsy J.

Subjects
Systemic lupus erythematosus -- Genetic aspects -- Development and progression -- Care and treatment, Genetic variation -- Health aspects, Transcription factors -- Health aspects, Health care industry
Abstract

The transcription factor IFN regulatory factor 5 (IRF5) is a central mediator of innate and adaptive immunity. Genetic variations within IRF5 are associated with a risk of systemic lupus erythematosus (SLE), and mice lacking Irf5 are protected from lupus onset and severity, but how IRF5 functions in the context of SLE disease progression remains unclear. Using the NZB/W F1 model of murine lupus, we show that murine IRF5 becomes hyperactivated before clinical onset. In patients with SLE, IRF5 hyperactivation correlated with dsDNA titers. To test whether IRF5 hyperactivation is a targetable function, we developed inhibitors that are cell permeable, nontoxic, and selectively bind to the inactive IRF5 monomer. Preclinical treatment of NZB/W F1 mice with an inhibitor attenuated lupus pathology by reducing serum antinuclear autoantibodies, dsDNA titers, and the number of circulating plasma cells, which alleviated kidney pathology and improved survival. Clinical treatment of MRL/lpr and pristane-induced lupus mice with an inhibitor led to significant reductions in dsDNA levels and improved survival. In ex vivo human studies, the inhibitor blocked SLE serum-induced IRF5 activation and reversed basal IRF5 hyperactivation in SLE immune cells. We believe this study provides the first in vivo clinical support for treating patients with SLE with an IRF5 inhibitor., Introduction Systemic lupus erythematosus (SLE) is a debilitating systemic autoimmune disease characterized by elevated levels of circulating antinuclear autoantibodies (ANAs) and severe immune dysregulation. Immune dysregulation may be conferred by [...]

Published
2020
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25. The Fourth Bioelectronic Medicine Summit “Technology Targeting Molecular Mechanisms”: current progress, challenges, and charting the future

Author

Datta-Chaudhuri, Timir, Zanos, Theodoros, Chang, Eric H., Olofsson, Peder S., Bickel, Stephan, Bouton, Chad, Grande, Daniel, Rieth, Loren, Aranow, Cynthia, Bloom, Ona, Mehta, Ashesh D., Civillico, Gene, Stevens, Molly M., Głowacki, Eric, Bettinger, Christopher, Schüettler, Martin, Puleo, Chris, Rennaker, Robert, Mohanta, Saroj, Carnevale, Daniela, Conde, Silvia V., Bonaz, Bruno, Chernoff, David, Kapa, Suraj, Berggren, Magnus, Ludwig, Kip, Zanos, Stavros, Miller, Larry, Weber, Doug, Yoshor, Daniel, Steinman, Lawrence, Chavan, Sangeeta S., Pavlov, Valentin A., Al-Abed, Yousef, and Tracey, Kevin J.

Published
2021
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32. Multi-Drug Cocktail Therapy Improves Survival and Neurological Function after Asphyxial Cardiac Arrest in Rodents

Author

Choudhary, Rishabh C., primary, Shoaib, Muhammad, additional, Hayashida, Kei, additional, Yin, Tai, additional, Miyara, Santiago J., additional, d’Abramo, Cristina, additional, Heuser, William G., additional, Shinozaki, Koichiro, additional, Kim, Nancy, additional, Takegawa, Ryosuke, additional, Nishikimi, Mitsuaki, additional, Li, Timmy, additional, Owens, Casey, additional, Molmenti, Ernesto P., additional, He, Mingzhu, additional, Vanpatten, Sonya, additional, Al-Abed, Yousef, additional, Kim, Junhwan, additional, and Becker, Lance B., additional

Published
2023
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50. Supplementary Fig. S4 from The antitumor properties of a nontoxic, nitric oxide–modified version of saquinavir are independent of Akt

Author

Maksimovic-Ivanic, Danijela, primary, Mijatovic, Sanja, primary, Miljkovic, Djordje, primary, Harhaji-Trajkovic, Ljubica, primary, Timotijevic, Gordana, primary, Mojic, Marija, primary, Dabideen, Darrin, primary, Cheng, Kai Fan, primary, McCubrey, James A., primary, Mangano, Katia, primary, Al-Abed, Yousef, primary, Libra, Massimo, primary, Garotta, Gianni, primary, Stosic-Grujicic, Stanislava, primary, and Nicoletti, Ferdinando, primary

Published
2023
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