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Translational Medical Research Commons™
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Articles 1 - 3 of 3
Full-Text Articles in Translational Medical Research
The Er Stress/Upr Axis In Chronic Obstructive Pulmonary Disease And Idiopathic Pulmonary Fibrosis., Mahmoud Aghaei, Sanaz Dastghaib, Sajjad Aftabi, Mohamad-Reza Aghanoori, Javad Alizadeh, Pooneh Mokarram, Parvaneh Mehrbod, Milad Ashrafizadeh, Ali Zarrabi, Kielan Darcy Mcalinden, Mathew Suji Eapen, Sukhwinder Singh Sohal, Pawan Sharma, Amir A Zeki, Saeid Ghavami
The Er Stress/Upr Axis In Chronic Obstructive Pulmonary Disease And Idiopathic Pulmonary Fibrosis., Mahmoud Aghaei, Sanaz Dastghaib, Sajjad Aftabi, Mohamad-Reza Aghanoori, Javad Alizadeh, Pooneh Mokarram, Parvaneh Mehrbod, Milad Ashrafizadeh, Ali Zarrabi, Kielan Darcy Mcalinden, Mathew Suji Eapen, Sukhwinder Singh Sohal, Pawan Sharma, Amir A Zeki, Saeid Ghavami
Center for Translational Medicine Faculty Papers
Cellular protein homeostasis in the lungs is constantly disrupted by recurrent exposure to various external and internal stressors, which may cause considerable protein secretion pressure on the endoplasmic reticulum (ER), resulting in the survival and differentiation of these cell types to meet the increased functional demands. Cells are able to induce a highly conserved adaptive mechanism, known as the unfolded protein response (UPR), to manage such stresses. UPR dysregulation and ER stress are involved in numerous human illnesses, such as metabolic syndrome, fibrotic diseases, and neurodegeneration, and cancer. Therefore, effective and specific compounds targeting the UPR pathway are being considered …
Simvastatin Induces Unfolded Protein Response And Enhances Temozolomide-Induced Cell Death In Glioblastoma Cells., Sanaz Dastghaib, Shahla Shojaei, Zohreh Mostafavi-Pour, Pawan Sharma, John B Patterson, Afshin Samali, Pooneh Mokarram, Saeid Ghavami
Simvastatin Induces Unfolded Protein Response And Enhances Temozolomide-Induced Cell Death In Glioblastoma Cells., Sanaz Dastghaib, Shahla Shojaei, Zohreh Mostafavi-Pour, Pawan Sharma, John B Patterson, Afshin Samali, Pooneh Mokarram, Saeid Ghavami
Center for Translational Medicine Faculty Papers
Glioblastoma (GBM) is the most prevalent malignant primary brain tumor with a very poor survival rate. Temozolomide (TMZ) is the common chemotherapeutic agent used for GBM treatment. We recently demonstrated that simvastatin (Simva) increases TMZ-induced apoptosis via the inhibition of autophagic flux in GBM cells. Considering the role of the unfolded protein response (UPR) pathway in the regulation of autophagy, we investigated the involvement of UPR in Simva-TMZ-induced cell death by utilizing highly selective IRE1 RNase activity inhibitor MKC8866, PERK inhibitor GSK-2606414 (PERKi), and eIF2α inhibitor salubrinal. Simva-TMZ treatment decreased the viability of GBM cells and significantly increased apoptotic cell …
Metformin Enhances Autophagy And Normalizes Mitochondrial Function To Alleviate Aging-Associated Inflammation, Leena P. Bharath, Madhur Agrawal, Grace Mccambridge, Dequina A. Nicholas, Hatice Hasturk, Jing Liu, Lao Jiang, Rui Liu, Zhenheng Guo, Jude T. Deeney, Caroline M. Apovian, Jennifer Snyder-Cappione, Gregory S. Hawk, Rebecca M. Fleeman, Riley M. F. Pihl, Katherine Thompson, Anna C. Belkina, Licong Cui, Elizabeth A. Proctor, Philip A. Kern, Barbara S. Nikolajczyk
Metformin Enhances Autophagy And Normalizes Mitochondrial Function To Alleviate Aging-Associated Inflammation, Leena P. Bharath, Madhur Agrawal, Grace Mccambridge, Dequina A. Nicholas, Hatice Hasturk, Jing Liu, Lao Jiang, Rui Liu, Zhenheng Guo, Jude T. Deeney, Caroline M. Apovian, Jennifer Snyder-Cappione, Gregory S. Hawk, Rebecca M. Fleeman, Riley M. F. Pihl, Katherine Thompson, Anna C. Belkina, Licong Cui, Elizabeth A. Proctor, Philip A. Kern, Barbara S. Nikolajczyk
Clinical and Translational Science Faculty Publications
Age is a non-modifiable risk factor for the inflammation that underlies age-associated diseases; thus, anti-inflammaging drugs hold promise for increasing health span. Cytokine profiling and bioinformatic analyses showed that Th17 cytokine production differentiates CD4+ T cells from lean, normoglycemic older and younger subjects, and mimics a diabetes-associated Th17 profile. T cells from older compared to younger subjects also had defects in autophagy and mitochondrial bioenergetics that associate with redox imbalance. Metformin ameliorated the Th17 inflammaging profile by increasing autophagy and improving mitochondrial bioenergetics. By contrast, autophagy-targeting siRNA disrupted redox balance in T cells from young subjects and activated the Th17 …