Supply Chain Resilience: Impact of Stakeholder Behavior and Trustworthy Information Sharing with a Case Study on Pharmaceutical Supply Chains

Ergün, Özlem; Griffin, Jacqueline; Chicoine, Noah; Min, Gong,; Mohaddesi, Omid; Raziei, Zohreh; Harteveld, Casper; Kaeli, David; Marsella, Stacy

doi:10.1287/educ.2022.0246

Cited by 2 publications

(1 citation statement)

References 75 publications

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“…In the worst case scenario, the capacity reduction caused by the unexpected disruption can result in a drug shortage (U.S. Food & Drug Administration 2019). Since facilities are only required to report when production is interrupted or permanently discontinued, inspections are essential to ensuring that risk factors that could lead to disruptions are appropriately mitigated (Ergun et al 2022, U.S. Food & Drug Administration 2020c, National Academies of Sciences, Engineering, and Medicine 2022).…”

Section: Introductionmentioning

confidence: 99%

Role of Stress Granules in the Pathogenesis of Pulmonary Hypertension Kosmas Kosmas ^1,2, Fotios Spyropoulos^1,2,Helen Christou ^1,2¹Department of Pediatric Newborn Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA ²Harvard Medical School, Boston, MA 02215, USA

2022

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Background PAH is a devastating and incurable disease characterized by abnormal pulmonary vascular phenotypes and progressive right ventricular failure, but the underlying mechanisms are incompletely understood. There is an urgent need of new therapeutic approaches, and a better understanding of disease pathogenesis is essential in identifying novel pathways that can be therapeutically targeted. Stress granules (SGs) are small intracellular structures that form in response to stress and contain mRNA molecules and mRNA‐binding proteins. These granules allow cells to temporarily halt translation by “parking” or sequestering certain mRNAs in a protected zone (the stress granule) and this allows the cells to survive in conditions of stress. The role of SGs in abnormal vascular and cardiac homeostasis in PAH is not known. Hypotheses We hypothesized that increased SG formation may contribute to both abnormal vascular cellular phenotypes and cardiac failure in human and experimental PAH. Further, we examined whether treatment with the carbonic anhydrase Acetazolamide (ACTZ) which is known to ameliorate experimental PAH, would alter SG tissue abundance in the lungs and heart. Methods We used the adult rat (Sprague Dawley) sugen/hypoxia (Su/Hx) model of severe pulmonary hypertension and studied tissue sections from lungs, heart and skeletal muscle as well as isolated primary pulmonary artery smooth muscle cells (PASMCs). We also used PASMCs from patients with PAH. We applied a combination of immunofluorescence and protein expression studies as well as drug (ACTZ) treatment and in vitro induction of oxidative stress (arsenite) to assess SG formation and SG related markers in experimental PAH and the effect of ACTZ. Results We have discovered that PASMCs from patients with PAH have a higher number of stress granules in response to oxidative stress than cells from normal individuals. We also found that PASMCs from a preclinical model of PAH (Sugen/Hypoxia) have more stress granules and increased SG components in response to oxidative stress compared to normal animals. Further, we found that treatment of PASMCs with ACTZ resulted in lower number of stress granules after cell stress. In addition, we found increased G3BP1 (key component of SG assembly) puncta in alveoli and bronchi and sarcoplasmic G3BP1 puncta in cardiac and soleus muscles from the rat sugen/hypoxia (Su/Hx) model compared to controls and with ACTZ treatment. Conclusions We conclude that there is increased SG formation in PASMCs and tissues in experimental PAH and acetazolamide inhibits stress granule assembly in response to oxidative stress. Further studies are needed to define the role of SG in disease pathogenesis, and evaluate whether targeting stress granules may be effective in restoring normal cellular function and improving PAH.

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Section: Introductionmentioning

confidence: 99%

Role of Stress Granules in the Pathogenesis of Pulmonary Hypertension Kosmas Kosmas ^1,2, Fotios Spyropoulos^1,2,Helen Christou ^1,2¹Department of Pediatric Newborn Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA ²Harvard Medical School, Boston, MA 02215, USA

2022

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Municipal supply chain performance through information sharing and stakeholder collaboration

Ngxesha,

Langton,

Mafini

2024

South African Journal of Economic and management Sciences

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Supply Chain Resilience: Impact of Stakeholder Behavior and Trustworthy Information Sharing with a Case Study on Pharmaceutical Supply Chains

Cited by 2 publications

References 75 publications

Role of Stress Granules in the Pathogenesis of Pulmonary Hypertension Kosmas Kosmas ^1,2, Fotios Spyropoulos^1,2,Helen Christou ^1,2¹Department of Pediatric Newborn Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA ²Harvard Medical School, Boston, MA 02215, USA

Role of Stress Granules in the Pathogenesis of Pulmonary Hypertension Kosmas Kosmas ^1,2, Fotios Spyropoulos^1,2,Helen Christou ^1,2¹Department of Pediatric Newborn Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA ²Harvard Medical School, Boston, MA 02215, USA

Municipal supply chain performance through information sharing and stakeholder collaboration

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Supply Chain Resilience: Impact of Stakeholder Behavior and Trustworthy Information Sharing with a Case Study on Pharmaceutical Supply Chains

Cited by 2 publications

References 75 publications

Role of Stress Granules in the Pathogenesis of Pulmonary Hypertension Kosmas Kosmas 1,2, Fotios Spyropoulos1,2,Helen Christou 1,21Department of Pediatric Newborn Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA 2Harvard Medical School, Boston, MA 02215, USA

Role of Stress Granules in the Pathogenesis of Pulmonary Hypertension Kosmas Kosmas 1,2, Fotios Spyropoulos1,2,Helen Christou 1,21Department of Pediatric Newborn Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA 2Harvard Medical School, Boston, MA 02215, USA

Municipal supply chain performance through information sharing and stakeholder collaboration

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Resources

About

Role of Stress Granules in the Pathogenesis of Pulmonary Hypertension Kosmas Kosmas ^1,2, Fotios Spyropoulos^1,2,Helen Christou ^1,2¹Department of Pediatric Newborn Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA ²Harvard Medical School, Boston, MA 02215, USA

Role of Stress Granules in the Pathogenesis of Pulmonary Hypertension Kosmas Kosmas ^1,2, Fotios Spyropoulos^1,2,Helen Christou ^1,2¹Department of Pediatric Newborn Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA ²Harvard Medical School, Boston, MA 02215, USA