The Interleukin-11/IL-11 receptor promotes glioblastoma survival and invasion under glucose-starved conditions through enhanced glutaminolysis
- Stuart, Sarah, Bezawork-Geleta, Ayenachew, Areeb, Zammam, Gomez, Juliana, Tsui, Vanessa, Zulkifli, Ahmad, Paradiso, Lucia, Jones, Jordan, Nguyen, Hong, Putoczki, Tracy, Licciardi, Paul, Kannourakis, George, Morokoff, Andrew, Achuthan, Adrian, Luwor, Rodney
- Authors: Stuart, Sarah , Bezawork-Geleta, Ayenachew , Areeb, Zammam , Gomez, Juliana , Tsui, Vanessa , Zulkifli, Ahmad , Paradiso, Lucia , Jones, Jordan , Nguyen, Hong , Putoczki, Tracy , Licciardi, Paul , Kannourakis, George , Morokoff, Andrew , Achuthan, Adrian , Luwor, Rodney
- Date: 2023
- Type: Text , Journal article
- Relation: International Journal of Molecular Sciences Vol. 24, no. 4 (2023), p.
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- Description: Glioblastoma cells adapt to changes in glucose availability through metabolic plasticity allowing for cell survival and continued progression in low-glucose concentrations. However, the regulatory cytokine networks that govern the ability to survive in glucose-starved conditions are not fully defined. In the present study, we define a critical role for the IL-11/IL-11R
- Authors: Stuart, Sarah , Bezawork-Geleta, Ayenachew , Areeb, Zammam , Gomez, Juliana , Tsui, Vanessa , Zulkifli, Ahmad , Paradiso, Lucia , Jones, Jordan , Nguyen, Hong , Putoczki, Tracy , Licciardi, Paul , Kannourakis, George , Morokoff, Andrew , Achuthan, Adrian , Luwor, Rodney
- Date: 2023
- Type: Text , Journal article
- Relation: International Journal of Molecular Sciences Vol. 24, no. 4 (2023), p.
- Full Text:
- Reviewed:
- Description: Glioblastoma cells adapt to changes in glucose availability through metabolic plasticity allowing for cell survival and continued progression in low-glucose concentrations. However, the regulatory cytokine networks that govern the ability to survive in glucose-starved conditions are not fully defined. In the present study, we define a critical role for the IL-11/IL-11R
Aerosol delivery of palivizumab in a neonatal lamb model of respiratory syncytial virus infection
- Edirisinghe, Hasindu, Rajapaksa, Anushi, Royce, Simon, Sourial, Magdy, Bischof, Robert, Anderson, Jeremy, Sarila, Gulcan, Nguyen, Cattram, Mulholland, Kim, Do, Lien, Licciardi, Paul
- Authors: Edirisinghe, Hasindu , Rajapaksa, Anushi , Royce, Simon , Sourial, Magdy , Bischof, Robert , Anderson, Jeremy , Sarila, Gulcan , Nguyen, Cattram , Mulholland, Kim , Do, Lien , Licciardi, Paul
- Date: 2023
- Type: Text , Journal article
- Relation: Viruses Vol. 15, no. 11 (2023), p.
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- Description: (1) Background: Palivizumab has been an approved preventative monoclonal antibody for respiratory syncytial virus (RSV) infection for over two decades. However, due to its high cost and requirement for multiple intramuscular injections, its use has been limited mostly to high-income countries. Following our previous study showing the successful lung deposition of aerosolised palivizumab in lambs, this current study evaluated the “proof-of-principle” effect of aerosolised palivizumab delivered as a therapeutic to neonatal lambs following RSV infection. (2) Methods: Neonatal lambs were intranasally inoculated with RSV-A2 on day 0 (day 3 post-birth) and treated with aerosolised palivizumab 3 days later (day 3 post-inoculation). Clinical symptoms, RSV viral load and inflammatory response were measured post-inoculation. (3) Results: Aerosolised therapeutic delivery of palivizumab did not reduce RSV viral loads in the nasopharynx nor the bronchoalveolar lavage fluid, but resulted in a modest reduction in inflammatory response at day 6 post-inoculation compared with untreated lambs. (4) Conclusions: This proof-of-principle study shows some evidence of aerosolised palivizumab reducing RSV inflammation, but further studies using optimized protocols are needed in order to validate these findings. © 2023 by the authors.
- Authors: Edirisinghe, Hasindu , Rajapaksa, Anushi , Royce, Simon , Sourial, Magdy , Bischof, Robert , Anderson, Jeremy , Sarila, Gulcan , Nguyen, Cattram , Mulholland, Kim , Do, Lien , Licciardi, Paul
- Date: 2023
- Type: Text , Journal article
- Relation: Viruses Vol. 15, no. 11 (2023), p.
- Full Text:
- Reviewed:
- Description: (1) Background: Palivizumab has been an approved preventative monoclonal antibody for respiratory syncytial virus (RSV) infection for over two decades. However, due to its high cost and requirement for multiple intramuscular injections, its use has been limited mostly to high-income countries. Following our previous study showing the successful lung deposition of aerosolised palivizumab in lambs, this current study evaluated the “proof-of-principle” effect of aerosolised palivizumab delivered as a therapeutic to neonatal lambs following RSV infection. (2) Methods: Neonatal lambs were intranasally inoculated with RSV-A2 on day 0 (day 3 post-birth) and treated with aerosolised palivizumab 3 days later (day 3 post-inoculation). Clinical symptoms, RSV viral load and inflammatory response were measured post-inoculation. (3) Results: Aerosolised therapeutic delivery of palivizumab did not reduce RSV viral loads in the nasopharynx nor the bronchoalveolar lavage fluid, but resulted in a modest reduction in inflammatory response at day 6 post-inoculation compared with untreated lambs. (4) Conclusions: This proof-of-principle study shows some evidence of aerosolised palivizumab reducing RSV inflammation, but further studies using optimized protocols are needed in order to validate these findings. © 2023 by the authors.
Moxonidine increases uptake of oxidised low-density lipoprotein in cultured vascular smooth muscle cells and inhibits atherosclerosis in apolipoprotein E-deficient mice
- Wang, Yutang, Nguyen, Dinh, Anesi, Jack, Alramahi, Ahmed, Witting, Paul, Chai, Zhonglin, Khan, Abdul, Kelly, Jason, Denton, Kate, Golledge, Jonathan
- Authors: Wang, Yutang , Nguyen, Dinh , Anesi, Jack , Alramahi, Ahmed , Witting, Paul , Chai, Zhonglin , Khan, Abdul , Kelly, Jason , Denton, Kate , Golledge, Jonathan
- Date: 2023
- Type: Text , Journal article
- Relation: International Journal of Molecular Sciences Vol. 24, no. 4 (2023), p.
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
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- Description: This study aimed to investigate the effect of the sympatholytic drug moxonidine on atherosclerosis. The effects of moxonidine on oxidised low-density lipoprotein (LDL) uptake, inflammatory gene expression and cellular migration were investigated in vitro in cultured vascular smooth muscle cells (VSMCs). The effect of moxonidine on atherosclerosis was measured by examining aortic arch Sudan IV staining and quantifying the intima-to-media ratio of the left common carotid artery in apolipoprotein E-deficient (ApoE
- Authors: Wang, Yutang , Nguyen, Dinh , Anesi, Jack , Alramahi, Ahmed , Witting, Paul , Chai, Zhonglin , Khan, Abdul , Kelly, Jason , Denton, Kate , Golledge, Jonathan
- Date: 2023
- Type: Text , Journal article
- Relation: International Journal of Molecular Sciences Vol. 24, no. 4 (2023), p.
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: This study aimed to investigate the effect of the sympatholytic drug moxonidine on atherosclerosis. The effects of moxonidine on oxidised low-density lipoprotein (LDL) uptake, inflammatory gene expression and cellular migration were investigated in vitro in cultured vascular smooth muscle cells (VSMCs). The effect of moxonidine on atherosclerosis was measured by examining aortic arch Sudan IV staining and quantifying the intima-to-media ratio of the left common carotid artery in apolipoprotein E-deficient (ApoE
Effect of hydralazine on angiotensin II-induced abdominal aortic aneurysm in apolipoprotein e-deficient mice
- Wang, Yutang, Sargisson, Owen, Nguyen, Dinh, Parker, Ketura, Pyke, Stephan, Alramahi, Ahmed, Thihlum, Liam, Fang, Yan, Wallace, Morgan, Berzins, Stuart, Oqueli, Ernesto, Magliano, Dianna, Golledge, Jonathan
- Authors: Wang, Yutang , Sargisson, Owen , Nguyen, Dinh , Parker, Ketura , Pyke, Stephan , Alramahi, Ahmed , Thihlum, Liam , Fang, Yan , Wallace, Morgan , Berzins, Stuart , Oqueli, Ernesto , Magliano, Dianna , Golledge, Jonathan
- Date: 2023
- Type: Text , Journal article
- Relation: International Journal of Molecular Sciences Vol. 24, no. 21 (2023), p.
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
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- Description: The rupture of an abdominal aortic aneurysm (AAA) causes about 200,000 deaths worldwide each year. However, there are currently no effective drug therapies to prevent AAA formation or, when present, to decrease progression and rupture, highlighting an urgent need for more research in this field. Increased vascular inflammation and enhanced apoptosis of vascular smooth muscle cells (VSMCs) are implicated in AAA formation. Here, we investigated whether hydralazine, which has anti-inflammatory and anti-apoptotic properties, inhibited AAA formation and pathological hallmarks. In cultured VSMCs, hydralazine (100
- Authors: Wang, Yutang , Sargisson, Owen , Nguyen, Dinh , Parker, Ketura , Pyke, Stephan , Alramahi, Ahmed , Thihlum, Liam , Fang, Yan , Wallace, Morgan , Berzins, Stuart , Oqueli, Ernesto , Magliano, Dianna , Golledge, Jonathan
- Date: 2023
- Type: Text , Journal article
- Relation: International Journal of Molecular Sciences Vol. 24, no. 21 (2023), p.
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: The rupture of an abdominal aortic aneurysm (AAA) causes about 200,000 deaths worldwide each year. However, there are currently no effective drug therapies to prevent AAA formation or, when present, to decrease progression and rupture, highlighting an urgent need for more research in this field. Increased vascular inflammation and enhanced apoptosis of vascular smooth muscle cells (VSMCs) are implicated in AAA formation. Here, we investigated whether hydralazine, which has anti-inflammatory and anti-apoptotic properties, inhibited AAA formation and pathological hallmarks. In cultured VSMCs, hydralazine (100
Sympathetic nervous system and atherosclerosis
- Wang, Yutang, Anesi, Jack, Maier, Michelle, Myers, Mark, Oqueli, Ernesto, Sobey, Christopher, Drummond, Grant, Denton, Kate
- Authors: Wang, Yutang , Anesi, Jack , Maier, Michelle , Myers, Mark , Oqueli, Ernesto , Sobey, Christopher , Drummond, Grant , Denton, Kate
- Date: 2023
- Type: Text , Journal article , Review
- Relation: International Journal of Molecular Sciences Vol. 24, no. 17 (2023), p.
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: Atherosclerosis is characterized by the narrowing of the arterial lumen due to subendothelial lipid accumulation, with hypercholesterolemia being a major risk factor. Despite the recent advances in effective lipid-lowering therapies, atherosclerosis remains the leading cause of mortality globally, highlighting the need for additional therapeutic strategies. Accumulating evidence suggests that the sympathetic nervous system plays an important role in atherosclerosis. In this article, we reviewed the sympathetic innervation in the vasculature, norepinephrine synthesis and metabolism, sympathetic activity measurement, and common signaling pathways of sympathetic activation. The focus of this paper was to review the effectiveness of pharmacological antagonists or agonists of adrenoceptors (
- Authors: Wang, Yutang , Anesi, Jack , Maier, Michelle , Myers, Mark , Oqueli, Ernesto , Sobey, Christopher , Drummond, Grant , Denton, Kate
- Date: 2023
- Type: Text , Journal article , Review
- Relation: International Journal of Molecular Sciences Vol. 24, no. 17 (2023), p.
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: Atherosclerosis is characterized by the narrowing of the arterial lumen due to subendothelial lipid accumulation, with hypercholesterolemia being a major risk factor. Despite the recent advances in effective lipid-lowering therapies, atherosclerosis remains the leading cause of mortality globally, highlighting the need for additional therapeutic strategies. Accumulating evidence suggests that the sympathetic nervous system plays an important role in atherosclerosis. In this article, we reviewed the sympathetic innervation in the vasculature, norepinephrine synthesis and metabolism, sympathetic activity measurement, and common signaling pathways of sympathetic activation. The focus of this paper was to review the effectiveness of pharmacological antagonists or agonists of adrenoceptors (
Animal models, pathogenesis, and potential treatment of thoracic aortic aneurysm
- Wang, Yutang, Panicker, Indu, Anesi, Jack, Sargisson, Owen, Atchison, Benjamin, Habenicht, Andreas
- Authors: Wang, Yutang , Panicker, Indu , Anesi, Jack , Sargisson, Owen , Atchison, Benjamin , Habenicht, Andreas
- Date: 2024
- Type: Text , Journal article , Review
- Relation: International Journal of Molecular Sciences Vol. 25, no. 2 (2024), p.
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: Thoracic aortic aneurysm (TAA) has a prevalence of 0.16–0.34% and an incidence of 7.6 per 100,000 person-years, accounting for 1–2% of all deaths in Western countries. Currently, no effective pharmacological therapies have been identified to slow TAA development and prevent TAA rupture. Large TAAs are treated with open surgical repair and less invasive thoracic endovascular aortic repair, both of which have high perioperative mortality risk. Therefore, there is an urgent medical need to identify the cellular and molecular mechanisms underlying TAA development and rupture to develop new therapies. In this review, we summarize animal TAA models including recent developments in porcine and zebrafish models: porcine models can assess new therapeutic devices or intervention strategies in a large mammal and zebrafish models can employ large-scale small-molecule suppressor screening in microwells. The second part of the review covers current views of TAA pathogenesis, derived from recent studies using these animal models, with a focus on the roles of the transforming growth factor-beta (TGF
- Authors: Wang, Yutang , Panicker, Indu , Anesi, Jack , Sargisson, Owen , Atchison, Benjamin , Habenicht, Andreas
- Date: 2024
- Type: Text , Journal article , Review
- Relation: International Journal of Molecular Sciences Vol. 25, no. 2 (2024), p.
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: Thoracic aortic aneurysm (TAA) has a prevalence of 0.16–0.34% and an incidence of 7.6 per 100,000 person-years, accounting for 1–2% of all deaths in Western countries. Currently, no effective pharmacological therapies have been identified to slow TAA development and prevent TAA rupture. Large TAAs are treated with open surgical repair and less invasive thoracic endovascular aortic repair, both of which have high perioperative mortality risk. Therefore, there is an urgent medical need to identify the cellular and molecular mechanisms underlying TAA development and rupture to develop new therapies. In this review, we summarize animal TAA models including recent developments in porcine and zebrafish models: porcine models can assess new therapeutic devices or intervention strategies in a large mammal and zebrafish models can employ large-scale small-molecule suppressor screening in microwells. The second part of the review covers current views of TAA pathogenesis, derived from recent studies using these animal models, with a focus on the roles of the transforming growth factor-beta (TGF
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