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1. A randomized, placebo-controlled trial of purified anthocyanins on cognitive function in individuals at elevated risk for dementia: Analysis of inflammatory biomarkers toward personalized interventions

Author

Borda, Miguel German, Barreto, George E., Baldera, Jonathan Patricio, de Lucia, Chiara, Khalifa, Khadija, Bergland, Anne Katrine, Pola, Ilaria, Botero-Rodríguez, Felipe, Siow, Richard C., Kivipelto, Miia, Zetterberg, Henrik, Ashton, Nicholas J., Ballard, Clive, and Aarsland, Dag

Published
2024
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6. Sexual dimorphism in COVID-19: potential clinical and public health implications

Author

Bechmann, Nicole, Barthel, Andreas, Schedl, Andreas, Herzig, Stephan, Varga, Zsuzsanna, Gebhard, Catherine, Mayr, Manuel, Hantel, Constanze, Beuschlein, Felix, Wolfrum, Christian, Perakakis, Nikolaos, Poston, Lucilla, Andoniadou, Cynthia L, Siow, Richard, Gainetdinov, Raul R, Dotan, Arad, Shoenfeld, Yehuda, Mingrone, Geltrude, and Bornstein, Stefan R

Published
2022
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7. Quantum healthy longevity from cells to cities.

Author

Woods, Tina, Palmarini, Nic, Corner, Lynne, and Siow, Richard

Subjects
HEALTH care reform, ATTITUDES toward aging, PSYCHOLOGICAL resilience, ECOLOGY, HEALTH expectancy, SOCIOECONOMIC factors, HEALTH equity, LONGEVITY, ACTIVE aging, BIOMARKERS, COGNITIVE aging
Published
2024
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8. A Randomised, Double-Blind, Placebo-Controlled, Cross-Over Clinical Trial to Evaluate the Biological Effects and Safety of a Polyphenol Supplement on Healthy Ageing.

Author

Chong, Joyce Ruifen, de Lucia, Chiara, Tovar-Rios, Diego Alejandro, Castellanos-Perilla, Nicolas, Collins, Christopher, Kvernberg, Silje Meihack, Ballard, Clive, Siow, Richard C., and Aarsland, Dag

Subjects
CROSSOVER trials, MEDITERRANEAN diet, BODY mass index, DNA methylation, OXIDATIVE stress
Abstract

DailyColors™ is a supplement made up of several phytonutrients that aims to replicate elements from the Mediterranean diet. These include fruit, berry and vegetable extracts that are rich in key phytochemicals such as Quercetin, Catechins, Phloretin, Ellagic Acid, and Anthocyanins. Here, we determined the effects of DailyColors™ on the blood biomarkers associated with the diverse mechanisms implicated in ageing and age-related diseases, including mitochondrial function, inflammation, and oxidative stress, as well as on saliva's DNA methylation pattern. Thirty adult participants (mean (SD) age = 67.0 (7.5) years) with a body mass index over 25 were recruited into this randomised, double-blind, placebo-controlled, cross-over trial (two one-week treatment periods, separated by a one-week washout period). During the placebo period, we observed a significant increase in blood CD38 concentrations from the baseline to 24 h (p-value = 0.019). This was not observed in the active period. Increased CD38 is reportedly associated with subsequent mitochondrial dysfunction and inflammation. Next, there was a decreasing trend of plasma 4-HNE levels, an oxidative stress biomarker, after a one-week intake of DailyColors™. Furthermore, following a one-month open-label follow-up in 26 participants, we observed hypermethylation of the candidate CpG site cg13108341 (q-value = 0.021), which was against the observed trend for this site during ageing. Taken together, while minimal effects were observed in this study, DailyColors™ supplementation may be beneficial by altering and alleviating age-related changes. Longer and larger scale trials of DailyColors™ supplementation are warranted. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Increased faecal shedding in SARS-CoV-2 variants BA.2.86 and JN.1

Author

Wannigama, Dhammika Leshan, primary, Amarasiri, Mohan, additional, Phattharapornjaroen, Phatthranit, additional, Hurst, Cameron, additional, Modchang, Charin, additional, Chadsuthi, Sudarat, additional, Anupong, Suparinthon, additional, Miyanaga, Kazuhiko, additional, Cui, Longzhu, additional, Fernandez, Stefan, additional, Huang, Angkana T, additional, Ounjai, Puey, additional, Singer, Andrew C, additional, Ragupathi, Naveen Kumar Devanga, additional, Sano, Daisuke, additional, Furukawa, Takashi, additional, Sei, Kazunari, additional, Leelahavanichkul, Asada, additional, Kanjanabuch, Talerngsak, additional, Chatsuwan, Tanittha, additional, Higgins, Paul G, additional, Nanbo, Asuka, additional, Kicic, Anthony, additional, Siow, Richard, additional, Trowsdale, Sam, additional, Hongsing, Parichart, additional, Khatib, Aisha, additional, Shibuya, Kenji, additional, Abe, Shuichi, additional, Ishikawa, Hitoshi, additional, Thuptiang, Wanwara, additional, Rad S.M., Ali Hosseini, additional, Vatanaprasan, Porames, additional, Jay, Dylan John, additional, Saethang, Thammakorn, additional, Luk-in, Sirirat, additional, Storer, Robin James, additional, Kanthawee, Phitsanuruk, additional, and Tacharoenmuang, Ratana, additional

Published
2024
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11. Meeting summary of The NYO3 5th NO-Age/AD meeting and the 1st Norway-UK joint meeting on ageing and dementia: recent progress on the mechanisms and interventional strategies

Author

Wang, He-Ling, Siow, Richard, Schmauck-Medina, Tomas, Zhang, Jianying, Sandset, Per Morten, Filshie, Clare, Lund, Øystein, Partridge, Linda, Bergersen, Linda Hildegard, Juel Rasmussen, Lene, Palikaras, Konstantinos, Sotiropoulos, Ioannis, Storm-Mathisen, Jon, Rubinsztein, David C, Spillantini, Maria Grazia, De Zeeuw, Chris I, Watne, Leiv Otto, Vyhnalek, Martin, Veverova, Katerina, Liang, Kristina Xiao, Tavernarakis, Nektarios, Bohr, Vilhelm A, Yokote, Koutaro, Saarela, Janna, Nilsen, Hilde, Gonos, Efstathios S, Scheibye-Knudsen, Morten, Chen, Guobing, Kato, Hisaya, Selbæk, Geir, Fladby, Tormod, Nilsson, Per, Simonsen, Anne, Aarsland, Dag, Lautrup, Sofie, Ottersen, Ole Petter, Cox, Lynne S, Fang, Evandro F, Wang, He-Ling, Siow, Richard, Schmauck-Medina, Tomas, Zhang, Jianying, Sandset, Per Morten, Filshie, Clare, Lund, Øystein, Partridge, Linda, Bergersen, Linda Hildegard, Juel Rasmussen, Lene, Palikaras, Konstantinos, Sotiropoulos, Ioannis, Storm-Mathisen, Jon, Rubinsztein, David C, Spillantini, Maria Grazia, De Zeeuw, Chris I, Watne, Leiv Otto, Vyhnalek, Martin, Veverova, Katerina, Liang, Kristina Xiao, Tavernarakis, Nektarios, Bohr, Vilhelm A, Yokote, Koutaro, Saarela, Janna, Nilsen, Hilde, Gonos, Efstathios S, Scheibye-Knudsen, Morten, Chen, Guobing, Kato, Hisaya, Selbæk, Geir, Fladby, Tormod, Nilsson, Per, Simonsen, Anne, Aarsland, Dag, Lautrup, Sofie, Ottersen, Ole Petter, Cox, Lynne S, and Fang, Evandro F

Abstract

Unhealthy ageing poses a global challenge with profound healthcare and socioeconomic implications. Slowing down the ageing process offers a promising approach to reduce the burden of a number of age-related diseases, such as dementia, promoting healthy longevity in the old population. In response to the challenge of the ageing population and with a view to the future, Norway and the UK are fostering collaborations, supported by a "Money Follows Cooperation agreement" between the two nations. The inaugural Norway-UK joint meeting on ageing and dementia gathered leading experts on ageing and dementia from the two nations to share their latest discoveries in related fields. Since ageing is an international challenge, and to foster collaborations, we also invited leading scholars from 11 additional countries to join this event. This report provides a summary of the conference, highlighting recent progress on molecular ageing mechanisms, genetic risk factors, DNA damage and repair, mitophagy, autophagy, as well as progress on a series of clinical trials (e.g., using NAD+ precursors). The meeting facilitated dialogue among policy makers, administrative leaders, researchers, and clinical experts, aiming to promote international research collaborations and to translate findings into clinical applications and interventions to advance healthy ageing.

Published
2024

12. Meeting Summary of The NYO3 5th NO-Age/AD Meeting and the 1st Norway-UK Joint Meeting on Aging and Dementia:Recent Progress on the Mechanisms and Interventional Strategies

Author

Wang, He Ling, Siow, Richard, Schmauck-Medina, Tomas, Zhang, Jianying, Sandset, Per Morten, Filshie, Clare, Lund, Øystein, Partridge, Linda, Bergersen, Linda Hildegard, Juel Rasmussen, Lene, Palikaras, Konstantinos, Sotiropoulos, Ioannis, Storm-Mathisen, Jon, Rubinsztein, David C., Spillantini, Maria Grazia, De Zeeuw, Chris I., Watne, Leiv Otto, Vyhnalek, Martin, Veverova, Katerina, Liang, Kristina Xiao, Tavernarakis, Nektarios, Bohr, Vilhelm A., Yokote, Koutaro, Saarela, Janna, Nilsen, Hilde, Gonos, Efstathios S., Scheibye-Knudsen, Morten, Chen, Guobing, Kato, Hisaya, Selbæk, Geir, Fladby, Tormod, Nilsson, Per, Simonsen, Anne, Aarsland, Dag, Lautrup, Sofie, Ottersen, Ole Petter, Cox, Lynne S., Fang, Evandro F., Wang, He Ling, Siow, Richard, Schmauck-Medina, Tomas, Zhang, Jianying, Sandset, Per Morten, Filshie, Clare, Lund, Øystein, Partridge, Linda, Bergersen, Linda Hildegard, Juel Rasmussen, Lene, Palikaras, Konstantinos, Sotiropoulos, Ioannis, Storm-Mathisen, Jon, Rubinsztein, David C., Spillantini, Maria Grazia, De Zeeuw, Chris I., Watne, Leiv Otto, Vyhnalek, Martin, Veverova, Katerina, Liang, Kristina Xiao, Tavernarakis, Nektarios, Bohr, Vilhelm A., Yokote, Koutaro, Saarela, Janna, Nilsen, Hilde, Gonos, Efstathios S., Scheibye-Knudsen, Morten, Chen, Guobing, Kato, Hisaya, Selbæk, Geir, Fladby, Tormod, Nilsson, Per, Simonsen, Anne, Aarsland, Dag, Lautrup, Sofie, Ottersen, Ole Petter, Cox, Lynne S., and Fang, Evandro F.

Abstract

Unhealthy aging poses a global challenge with profound healthcare and socioeconomic implications. Slowing down the aging process offers a promising approach to reduce the burden of a number of age-related diseases, such as dementia, and promoting healthy longevity in the old population. In response to the challenge of the aging population and with a view to the future, Norway and the United Kingdom are fostering collaborations, supported by a “Money Follows Cooperation agreement” between the 2 nations. The inaugural Norway–UK joint meeting on aging and dementia gathered leading experts on aging and dementia from the 2 nations to share their latest discoveries in related fields. Since aging is an international challenge, and to foster collaborations, we also invited leading scholars from 11 additional countries to join this event. This report provides a summary of the conference, highlighting recent progress on molecular aging mechanisms, genetic risk factors, DNA damage and repair, mitophagy, autophagy, as well as progress on a series of clinical trials (eg, using NAD+ precursors). The meeting facilitated dialogue among policymakers, administrative leaders, researchers, and clinical experts, aiming to promote international research collaborations and to translate findings into clinical applications and interventions to advance healthy aging., Unhealthy aging poses a global challenge with profound healthcare and socioeconomic implications. Slowing down the aging process offers a promising approach to reduce the burden of a number of age-related diseases, such as dementia, and promoting healthy longevity in the old population. In response to the challenge of the aging population and with a view to the future, Norway and the United Kingdom are fostering collaborations, supported by a "Money Follows Cooperation agreement" between the 2 nations. The inaugural Norway-UK joint meeting on aging and dementia gathered leading experts on aging and dementia from the 2 nations to share their latest discoveries in related fields. Since aging is an international challenge, and to foster collaborations, we also invited leading scholars from 11 additional countries to join this event. This report provides a summary of the conference, highlighting recent progress on molecular aging mechanisms, genetic risk factors, DNA damage and repair, mitophagy, autophagy, as well as progress on a series of clinical trials (eg, using NAD+ precursors). The meeting facilitated dialogue among policymakers, administrative leaders, researchers, and clinical experts, aiming to promote international research collaborations and to translate findings into clinical applications and interventions to advance healthy aging.

Published
2024

13. Increased faecal shedding in SARS-CoV-2 variants BA.2.86 and JN.1 [Correspondence]

Author

Wannigama, Dhammika Leshan, Amarasiri, Mohan, Phattharapornjaroen, Phatthranit, Hurst, Cameron, Modchang, Charin, Chadsuthi, Sudarat, Anupong, Suparinthon, Miyanaga, Kazuhiko, Cui, Longzhu, Fernandez, Stefan, Huang, Angkana T., Ounjai, Puey, Singer, Andrew C., Ragupathi, Naveen Kumar Devanga, Sano, Daisuke, Furukawa, Takashi, Sei, Kazunari, Leelahavanichkul, Asada, Kanjanabuch, Talerngsak, Chatsuwan, Tanittha, Higgins, Paul G., Nanbo, Asuka, Kicic, Anthony, Siow, Richard, Trowsdale, Sam, Hongsing, Parichart, Khatib, Aisha, Shibuya, Kenji, Abe, Shuichi, Ishikawa, Hitoshi, Thuptiang, Wanwara, Rad S.M., Ali Hosseini, Vatanaprasan, Porames, Jay, Dylan John, Saethang, Thammakorn, Luk-in, Sirirat, Storer, Robin James, Kanthawee, Phitsanuruk, Tacharoenmuang, Ratana, Wannigama, Dhammika Leshan, Amarasiri, Mohan, Phattharapornjaroen, Phatthranit, Hurst, Cameron, Modchang, Charin, Chadsuthi, Sudarat, Anupong, Suparinthon, Miyanaga, Kazuhiko, Cui, Longzhu, Fernandez, Stefan, Huang, Angkana T., Ounjai, Puey, Singer, Andrew C., Ragupathi, Naveen Kumar Devanga, Sano, Daisuke, Furukawa, Takashi, Sei, Kazunari, Leelahavanichkul, Asada, Kanjanabuch, Talerngsak, Chatsuwan, Tanittha, Higgins, Paul G., Nanbo, Asuka, Kicic, Anthony, Siow, Richard, Trowsdale, Sam, Hongsing, Parichart, Khatib, Aisha, Shibuya, Kenji, Abe, Shuichi, Ishikawa, Hitoshi, Thuptiang, Wanwara, Rad S.M., Ali Hosseini, Vatanaprasan, Porames, Jay, Dylan John, Saethang, Thammakorn, Luk-in, Sirirat, Storer, Robin James, Kanthawee, Phitsanuruk, and Tacharoenmuang, Ratana

Published
2024

14. The Longevity Med Summit: insights on healthspan from cell to society.

Author

Falshaw, Natalie, Sagner, Michael, and Siow, Richard C.

Subjects
DISEASE risk factors, CLINICAL medicine, PREVENTIVE medicine, RESEARCH personnel, ECONOMIC impact
Abstract

In recent years, there has been a paradigm shift with regards to ageing, challenging its traditional perception as an inevitable and natural process. Researchers have collectively identified hallmarks of ageing, nine of which were initially proposed in 2013 and expanded in 2023 to include disabled macroautophagy, chronic inflammation, and dysbiosis, enhancing our understanding of the ageing process at microscopic, cellular, and systemwide levels. Strategies to manipulate these hallmarks present opportunities for slowing, preventing, or reversing age-related diseases, thereby promoting longevity. The interdependence of these hallmarks underscores the necessity of a comprehensive, systems-based approach to address the complex processes contributing to ageing. As a primary risk factor for various diseases, ageing diminishes healthspan, leading to extended periods of compromised health and multiple age-related conditions towards the end of life. The significant gap between healthspan and lifespan holds substantial economic and societal implications. The inaugural Longevity Med Summit (4-5 May 2023, Cascais, Portugal) provided an international forum to discuss the academic and industry landscape of healthy longevity research, preventive medicine and clinical practice to enhance healthspan. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Meeting summary of The NYO3 5th NO-Age/AD meeting and the 1st Norway-UK joint meeting on ageing and dementia: recent progress on the mechanisms and interventional strategies

Author

Wang, He-Ling, primary, Siow, Richard, additional, Schmauck-Medina, Tomas, additional, Zhang, Jianying, additional, Sandset, Per Morten, additional, Filshie, Clare, additional, Lund, Øystein, additional, Partridge, Linda, additional, Bergersen, Linda Hildegard, additional, Juel Rasmussen, Lene, additional, Palikaras, Konstantinos, additional, Sotiropoulos, Ioannis, additional, Storm-Mathisen, Jon, additional, Rubinsztein, David C, additional, Spillantini, Maria Grazia, additional, De Zeeuw, Chris I, additional, Watne, Leiv Otto, additional, Vyhnalek, Martin, additional, Veverova, Katerina, additional, Liang, Kristina Xiao, additional, Tavernarakis, Nektarios, additional, Bohr, Vilhelm A, additional, Yokote, Koutaro, additional, Saarela, Janna, additional, Nilsen, Hilde, additional, Gonos, Efstathios S, additional, Scheibye-Knudsen, Morten, additional, Chen, Guobing, additional, Kato, Hisaya, additional, Selbæk, Geir, additional, Fladby, Tormod, additional, Nilsson, Per, additional, Simonsen, Anne, additional, Aarsland, Dag, additional, Lautrup, Sofie, additional, Ottersen, Ole Petter, additional, Cox, Lynne S, additional, and Fang, Evandro F, additional

Published
2024
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16. Community-based mpox and sexually transmitted disease surveillance using discarded condoms in the global south

Author

Werawatte, W.K.C.P., Rad S.M., Ali Hosseini, Vatanaprasan, Porames, Jay, Dylan John, Saethang, Thammakorn, Luk-in, Sirirat, Storer, Robin James, Kanthawee, Phitsanuruk, Al-Dois, Marily, Bani, Rapong, Thuptiang, Wanwara, Khan, Sifat, Tacharoenmuang, Ratana, Cynthia, Bernadina, Vitharana, S.P.H Spencer, Ngamwongsatit, Natharin, Ishikawa, Hitoshi, Wannigama, Dhammika Leshan, Amarasiri, Mohan, Phattharapornjaroen, Phatthranit, Hurst, Cameron, Modchang, Charin, Besa, John Jefferson V, Miyanaga, Kazuhiko, Cui, Longzhu, Fernandez, Stefan, Huang, Angkana T, Ounjai, Puey, Singer, Andrew C, Ragupathi, Naveen Kumar Devanga, Furukawa, Takashi, Sei, Kazunari, Nanbo, Asuka, Leelahavanichkul, Asada, Kanjanabuch, Talerngsak, Chatsuwan, Tanittha, Higgins, Paul G, Sano, Daisuke, Kicic, Anthony, Rockstroh, Jürgen Kurt, Siow, Richard, Trowsdale, Sam, Hongsing, Parichart, Khatib, Aisha, Shibuya, Kenji, and Abe, Shuichi

Published
2024
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17. Interactions between zinc and NRF2 in vascular redox signalling.

Author

Fan Yang, Smith, Matthew J., Siow, Richard C. M., Aarsland, Dag, Maret, Wolfgang, and Mann, Giovanni E.

Subjects
GLYCOGEN synthase kinase, NUCLEAR factor E2 related factor, MITOGEN-activated protein kinases, PROTEIN kinase C, GLUTATHIONE, NITRIC-oxide synthases
Abstract

Recent evidence highlights the importance of trace metal micronutrients such as zinc (Zn) in coronary and vascular diseases. Zn2+ plays a signalling role in modulating endothelial nitric oxide synthase and protects the endothelium against oxidative stress by upregulation of glutathione synthesis. Excessive accumulation of Zn2+ in endothelial cells leads to apoptotic cell death resulting from dysregulation of glutathione and mitochondrial ATP synthesis, whereas zinc deficiency induces an inflammatory phenotype, associated with increased monocyte adhesion. Nuclear factor-E2-related factor 2 (NRF2) is a transcription factor known to target hundreds of different genes. Activation of NRF2 affects redox metabolism, autophagy, cell proliferation, remodelling of the extracellular matrix and wound healing. As a redox-inert metal ion, Zn has emerged as a biomarker in diagnosis and as a therapeutic approach for oxidative-related diseases due to its close link to NRF2 signalling. In non-vascular cell types, Zn has been shown to modify conformations of the NRF2 negative regulators Kelch-like ECH-associated Protein 1 (KEAP1) and glycogen synthase kinase 3β (GSK3β) and to promote degradation of BACH1, a transcriptional suppressor of select NRF2 genes. Zn can affect phosphorylation signalling, including mitogen-activated protein kinases (MAPK), phosphoinositide 3-kinases and protein kinase C, which facilitate NRF2 phosphorylation and nuclear translocation. Notably, several NRF2-targeted proteins have been suggested to modify cellular Zn concentration via Zn exporters (ZnTs) and importers (ZIPs) and the Zn buffering protein metallothionein. This review summarises the cross-talk between reactive oxygen species, Zn and NRF2 in antioxidant responses of vascular cells against oxidative stress and hypoxia/reoxygenation. [ABSTRACT FROM AUTHOR]

Published
2024
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20. Increased faecal shedding in SARS-CoV-2 variants BA.2.86 and JN.1

Author

Thuptiang, Wanwara, Rad S.M., Ali Hosseini, Vatanaprasan, Porames, Jay, Dylan John, Saethang, Thammakorn, Luk-in, Sirirat, Storer, Robin James, Kanthawee, Phitsanuruk, Tacharoenmuang, Ratana, Wannigama, Dhammika Leshan, Amarasiri, Mohan, Phattharapornjaroen, Phatthranit, Hurst, Cameron, Modchang, Charin, Chadsuthi, Sudarat, Anupong, Suparinthon, Miyanaga, Kazuhiko, Cui, Longzhu, Fernandez, Stefan, Huang, Angkana T, Ounjai, Puey, Singer, Andrew C, Ragupathi, Naveen Kumar Devanga, Sano, Daisuke, Furukawa, Takashi, Sei, Kazunari, Leelahavanichkul, Asada, Kanjanabuch, Talerngsak, Chatsuwan, Tanittha, Higgins, Paul G, Nanbo, Asuka, Kicic, Anthony, Siow, Richard, Trowsdale, Sam, Hongsing, Parichart, Khatib, Aisha, Shibuya, Kenji, Abe, Shuichi, and Ishikawa, Hitoshi

Published
2024
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21. Vascular protection afforded by zinc supplementation in human coronary artery smooth muscle cells mediated by NRF2 signaling under hypoxia/reoxygenation:Zinc supplementation protects against hypoxia/reoxygenation

Author

Yang, Fan, Smith, Matthew, Griffiths, Alex, Morrell, Alexander, Chapple, Sarah, Siow, Richard, Stewart, Theodora, Maret, Wolfgang, and Mann, Giovanni

Subjects
Zinc, Physioxia, Human coronary artery smooth muscle cells, Hypoxia-reoxygenation, NRF2 redox signaling
Abstract

Zinc (Zn) has antioxidant, anti-inflammatory and anti-proliferative actions, with Zn dysregulation associated with coronary ischemia/reperfusion injury and smooth muscle cell dysfunction. As the majority of studies concerning Zn have been conducted under non-physiological hyperoxic conditions, we compare the effects of Zn chelation or supplementation on total intracellular Zn content, antioxidant NRF2 targeted gene transcription and hypoxia/reoxygenation-induced reactive oxygen species generation in human coronary artery smooth muscle cells (HCASMC) pre-adapted to hyperoxia (18 kPa O 2) or normoxia (5 kPa O 2). Expression of the smooth muscle marker SM22-α was unaffected by lowering pericellular O 2, whereas calponin-1 was significantly upregulated in cells under 5 kPa O 2, indicating a more physiological contractile phenotype under 5 kPa O 2. Inductively coupled plasma mass spectrometry established that Zn supplementation (10 μM ZnCl 2 + 0.5 μM pyrithione) significantly increased total Zn content in HCASMC under 18 but not 5 kPa O 2. Zn supplementation increased metallothionein mRNA expression and NRF2 nuclear accumulation in cells under 18 or 5 kPa O 2. Notably, NRF2 regulated HO-1 and NQO1 mRNA expression in response to Zn supplementation was only upregulated in cells under 18 but not 5 kPa. Furthermore, whilst hypoxia increased intracellular glutathione (GSH) in cells pre-adapted to 18 but not 5 kPa O 2, reoxygenation had negligible effects on GSH or total Zn content. Reoxygenation-induced superoxide generation in cells under 18 kPa O 2 was abrogated by PEG-superoxide dismutase but not by PEG-catalase, and Zn supplementation, but not Zn chelation, attenuated reoxygenation-induced superoxide generation in cells under 18 but not 5kPaO 2, consistent with a lower redox stress under physiological normoxia. Our findings highlight that culture of HCASMC under physiological normoxia recapitulates an in vivo contractile phenotype and that effects of Zn on NRF2 signaling are altered by oxygen tension.

Published
2023

22. Tracing the transmission of Mpox through wastewater surveillance in Southeast Asia

Author

Wannigama, Dhammika Leshan, primary, Amarasiri, Mohan, additional, Phattharapornjaroen, Phatthranit, additional, Hurst, Cameron, additional, Modchang, Charin, additional, Chadsuthi, Sudarat, additional, Anupong, Suparinthon, additional, Miyanaga, Kazuhiko, additional, Cui, Longzhu, additional, Thuptimdang, Wanwara, additional, Ali Hosseini Rad, S M, additional, Fernandez, Stefan, additional, Huang, Angkana T, additional, Vatanaprasan, Porames, additional, Jay, Dylan John, additional, Saethang, Thammakorn, additional, Luk-in, Sirirat, additional, Storer, Robin James, additional, Ounjai, Puey, additional, Ragupathi, Naveen Kumar Devanga, additional, Kanthawee, Phitsanuruk, additional, Sano, Daisuke, additional, Furukawa, Takashi, additional, Sei, Kazunari, additional, Leelahavanichkul, Asada, additional, Kanjanabuch, Talerngsak, additional, Higgins, Paul G, additional, Nanbo, Asuka, additional, Kicic, Anthony, additional, Singer, Andrew C, additional, Chatsuwan, Tanittha, additional, Trowsdale, Sam, additional, Siow, Richard, additional, Shibuya, Kenji, additional, Abe, Shuichi, additional, Ishikawa, Hitoshi, additional, and Hongsing, Parichart, additional

Published
2023
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24. Tracing the transmission of mpox through wastewater surveillance in Southeast Asia

Author

Wannigama, Dhammika Leshan, Amarasiri, Mohan, Phattharapornjaroen, Phatthranit, Hurst, Cameron, Modchang, Charin, Chadsuthi, Sudarat, Anupong, Suparinthon, Miyanaga, Kazuhiko, Cui, Longzhu, Thuptimdang, Wanwara, Ali Hosseini Rad, S.M., Fernandez, Stefan, Huang, Angkana T., Vatanaprasan, Porames, Jay, Dylan John, Saethang, Thammakorn, Luk-in, Sirirat, Storer, Robin James, Ounjai, Puey, Ragupathi, Naveen Kumar Devanga, Kanthawee, Phitsanuruk, Sano, Daisuke, Furukawa, Takashi, Sei, Kazunari, Leelahavanichkul, Asada, Kanjanabuch, Talerngsak, Higgins, Paul G., Nanbo, Asuka, Kicic, Anthony, Singer, Andrew C., Chatsuwan, Tanittha, Trowsdale, Sam, Siow, Richard, Shibuya, Kenji, Abe, Shuichi, Ishikawa, Hitoshi, Hongsing, Parichart, Wannigama, Dhammika Leshan, Amarasiri, Mohan, Phattharapornjaroen, Phatthranit, Hurst, Cameron, Modchang, Charin, Chadsuthi, Sudarat, Anupong, Suparinthon, Miyanaga, Kazuhiko, Cui, Longzhu, Thuptimdang, Wanwara, Ali Hosseini Rad, S.M., Fernandez, Stefan, Huang, Angkana T., Vatanaprasan, Porames, Jay, Dylan John, Saethang, Thammakorn, Luk-in, Sirirat, Storer, Robin James, Ounjai, Puey, Ragupathi, Naveen Kumar Devanga, Kanthawee, Phitsanuruk, Sano, Daisuke, Furukawa, Takashi, Sei, Kazunari, Leelahavanichkul, Asada, Kanjanabuch, Talerngsak, Higgins, Paul G., Nanbo, Asuka, Kicic, Anthony, Singer, Andrew C., Chatsuwan, Tanittha, Trowsdale, Sam, Siow, Richard, Shibuya, Kenji, Abe, Shuichi, Ishikawa, Hitoshi, and Hongsing, Parichart

Abstract

High population density and tourism in Southeast Asia increase the risk of mpox due to frequent interpersonal contacts. Our wastewater surveillance in six Southeast Asian countries revealed positive signals for Monkeypox virus (MPXV) DNA, indicating local transmission. This alerts clinicians and helps allocate resources like testing, vaccines and therapeutics in resource-limited countries.

Published
2023

26. Quantum Healthy Longevity for healthy people, planet, and growth

Author

Woods, Tina, primary, Palmarini, Nic, additional, Corner, Lynne, additional, Barzilai, Nir, additional, Bethell, Lord James, additional, Cox, Lynne S, additional, Eyre, Harris, additional, Ferrucci, Luigi, additional, Fried, Linda, additional, Furman, David, additional, Kennedy, Brian, additional, Roddam, Andrew, additional, Scott, Andrew, additional, and Siow, Richard C, additional

Published
2022
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36. Corrigendum: Effects of Anthocyanin Supplementation on Serum Lipids, Glucose, Markers of Inflammation and Cognition in Adults With Increased Risk of Dementia – A Pilot Study

Author

Bergland, Anne Katrine, primary, Soennesyn, Hogne, additional, Dalen, Ingvild, additional, Rodriguez-Mateos, Ana, additional, Berge, Rolf Kristian, additional, Giil, Lasse Melvaer, additional, Rajendran, Lawrence, additional, Siow, Richard, additional, Tassotti, Michele, additional, Larsen, Alf Inge, additional, and Aarsland, Dag, additional

Published
2021
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37. Advances in microfluidic in vitro systems for neurological disease modeling

Author

Holloway, Paul M., Willaime‐Morawek, Sandrine, Siow, Richard, Barber, Melissa, Owens, Róisín M., Sharma, Anup D., Rowan, Wendy, Hill, Eric, Zagnoni, Michele, Holloway, Paul M., Willaime‐Morawek, Sandrine, Siow, Richard, Barber, Melissa, Owens, Róisín M., Sharma, Anup D., Rowan, Wendy, Hill, Eric, and Zagnoni, Michele

Abstract

Neurological disorders are the leading cause of disability and the second largest cause of death worldwide. Despite significant research efforts, neurology remains one of the most failure‐prone areas of drug development. The complexity of the human brain, boundaries to examining the brain directly in vivo, and the significant evolutionary gap between animal models and humans, all serve to hamper translational success. Recent advances in microfluidic in vitro models have provided new opportunities to study human cells with enhanced physiological relevance. The ability to precisely micro‐engineer cell‐scale architecture, tailoring form and function, has allowed for detailed dissection of cell biology using microphysiological systems (MPS) of varying complexities from single cell systems to “Organ‐on‐chip” models. Simplified neuronal networks have allowed for unique insights into neuronal transport and neurogenesis, while more complex 3D heterotypic cellular models such as neurovascular unit mimetics and “Organ‐on‐chip” systems have enabled new understanding of metabolic coupling and blood–brain barrier transport. These systems are now being developed beyond MPS toward disease specific micro‐pathophysiological systems, moving from “Organ‐on‐chip” to “Disease‐on‐chip.” This review gives an outline of current state of the art in microfluidic technologies for neurological disease research, discussing the challenges and limitations while highlighting the benefits and potential of integrating technologies. We provide examples of where such toolsets have enabled novel insights and how these technologies may empower future investigation into neurological diseases.

Published
2021

41. Gestational diabetes mellitus impairs Nrf2-mediated adaptive antioxidant defenses and redox signaling in fetal endothelial cells in utero

Author

Cheng, Xinghua, Chapple, Sarah J., Patel, Bijal, Puszyk, William, Sugden, David, Yin, Xiaoke, Mayr, Manuel, Siow, Richard C.M., and Mann, Giovanni E.

Subjects
Gene expression -- Research, Diabetes -- Complications and side effects -- Risk factors -- Genetic aspects -- Research, Cardiovascular diseases -- Risk factors, Type 2 diabetes -- Risk factors, Health
Abstract

In utero exposure to gestational diabetes mellitus (GDM) is associated with an increased risk of type 2 diabetes and cardiovascular disease in later life, yet the underlying mechanisms remain to be elucidated. We examined the effects of GDM on the proteome, redox status, and nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant gene expression in human fetal endothelial cells. Proteomic analysis revealed that proteIns involved in redox homeostasis were significantly altered in GDM and associated with increased mitochondrial superoxide generation, protein oxidation, DNA damage, and diminished glutathione (GSH) synthesis. In GDM cells, the lipid peroxidation product 4-hydroxynonenal (HNE) failed to induce nuclear Nrf2 accumulation and mRNA and/or protein expression of Nrf2 and its target genes NAD(P)H:quinone oxidoreductase 1 (NQO1), Bachl, cystine/glutamate transporter, and glutamate cysteine ligase. Although methylation of CpG islands in Nrf2 or NQO1 promoters was unaltered by GDM, decreased DJ-1 and increased phosphorylated glycogen synthase kinase 3β levels may account for impaired Nrf2 signaling. HNE-induced increases in GSH and NQO1 levels were abrogated by Nrf2 small interfering RNA in normal cells, and overexpression of Nrf2 in GDM cells partially restored NQO1 induction. Dysregulation of Nrf2 in fetal endothelium may contribute to the increased risk of type 2 diabetes and cardiovascular disease in offspring., Endothelial cells are primary targets of hyperglycemia-induced oxidative damage (1), and elevated intracellular glucose levels increase mitochondrial superoxide generation, leading to activation of the polyol and hexosamine pathways and, ultimately, [...]

Published
2013
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42. Differential Expression of Insulin-Like Growth Factor 1 and Wnt Family Member 4 Correlates With Functional Heterogeneity of Human Dermal Fibroblasts

Author

Culley, Oliver J., primary, Louis, Blaise, additional, Philippeos, Christina, additional, Oulès, Bénédicte, additional, Tihy, Matthieu, additional, Segal, Joe M., additional, Hyliands, Della, additional, Jenkins, Gail, additional, Bhogal, Ranjit K., additional, Siow, Richard C., additional, and Watt, Fiona M., additional

Published
2021
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49. UVA irradiation increases ferrous iron release from human skin fibroblast and endothelial cell ferritin:Consequences for cell senescence and aging: UVA irradiation acutely induces Fe (II) loss from cell ferritin

Author

Smith, Matthew, Fowler, Mark, Naftalin, Richard, and Siow, Richard

Subjects
DFO, PEG-SOD, photon, Desferrioxamine, 3-amino-1, 2, 4-triazole, tetrathiomolybdate, Labile iron pool, superoxide dismutase, LIP, normal human dermal fibroblasts, HBSS, NHDF, Hank's buffered saline solution, degrees of freedom, ATM, riboflavin nucleotide, FMNH, dihydroriboflavin 5′-phosphate, ATZ, FMN, SOD, d.f, hν, Polyethylene glycolated superoxide dismutase
Abstract

UVA irradiation of human dermal fibroblasts and endothelial cells induces an immediate transient increase in cytosolic Fe(II), as monitored by the fluorescence Fe(II) reporters, FeRhonox1 in cytosol and MitoFerroGreen in mitochondria. Both superoxide dismutase (SOD) inhibition by tetrathiomolybdate (ATM) and catalase inhibition by 3-amino-1, 2, 4-triazole (ATZ) increase and prolong the cytosolic Fe(II) signal after UVA irradiation. SOD inhibition with ATM also increases mitochondrial Fe(II). Thus, mitochondria do not source the UV-dependent increase in cytosolic Fe(II), but instead reflect and amplify raised cytosolic labile Fe(II) concentration. Hence control of cytosolic ferritin iron release is key to preventing UVA-induced inflammation. UVA irradiation also increases dermal endothelial cell H 2O 2, as monitored by the adenovirus vector Hyper-DAAO-NES(HyPer). These UVA-dependent changes in intracellular Fe(II) and H 2O 2 are mirrored by increases in cell superoxide, monitored with the luminescence probe L-012. UV-dependent increases in cytosolic Fe(II), H 2O 2 and L-012 chemiluminescence are prevented by ZnCl 2 (10 μM), an effective inhibitor of Fe(II) transport via ferritin's 3-fold channels. Quercetin (10 μM), a potent membrane permeable Fe(II) chelator, abolishes the cytosolic UVA-dependent FeRhonox1, Fe(II) and HyPer, H 2O 2 and increase in MitoFerroGreen Fe(II) signals. The time course of the quercetin-dependent decrease in endothelial H 2O 2 correlates with the decrease in FeRhox1 signal and both signals are fully suppressed by preloading cells with ZnCl 2. These results confirm that antioxidant enzyme activity is the key factor in controlling intracellular iron levels, and hence maintenance of cell antioxidant capacity is vitally important in prevention of skin aging and inflammation initiated by labile iron and UVA.

Published
2020

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