title: Hyperglycaemia and oxidative stress upregulate HSP60 & HSP70 expression in HeLa cells

authors: Hall, Luke

subjects: HSP60

abstract: Heat Shock Proteins 60 & 70 (HSP60 & HSP70) are intracellular protein that has been shown to be present at elevated levels in systemic circulation in Type 2 Diabetes mellitus (T2DM) patients. Conditions that lead to its secretion, and the mechanism of its translocation from cells, have not yet been defined. The aim of this study was to determine if specific cell stressors associated with T2DM, namely hyperglycaemia and oxidative stress, result in the upregulation of HSP60 in human cells in vitro. Human HeLa cells were grown in media supplemented with 100 mM glucose, 200 μM hydrogen peroxide (H₂O₂), and 50 μM sodium azide. Initially, the effect of these treatments on cell growth rate was examined, with each treatment significantly inhibiting growth rate. LDH and MTT assays were also used to successfully demonstrate that these treatments do not significantly increase cell lysis, but do significantly impair mitochondrial dehydrogenase activity. To confirm this mitochondria specific form of inhibition, DCFDA assay were used to investigate any increases in intracellular reactive oxygen species (ROS) generation. All three treatments resulted in significantly increased ROS generation, with greater ROS production occurring with a greater exposure time. Interestingly, when the protein levels of HSP60 and HSP70 were measured after 3 and 7 days of exposure of the HeLa cells to 100 mM glucose, 200 μM H₂O₂, and 50 μM sodium azide significant induction of these two molecular stress proteins were observed ranging from 2.43-5.08 fold compared to untreated control cells.

text: Hyperglycaemia and oxidative stress upregulate HSP60 & HSP70 expression in HeLa cells Heat Shock Proteins 60 & 70 (HSP60 & HSP70) are intracellular protein that has been shown to be present at elevated levels in systemic circulation in Type 2 Diabetes mellitus (T2DM) patients. Conditions that lead to its secretion, and the mechanism of its translocation from cells, have not yet been defined. The aim of this study was to determine if specific cell stressors associated with T2DM, namely hyperglycaemia and oxidative stress, result in the upregulation of HSP60 in human cells in vitro. Human HeLa cells were grown in media supplemented with 100 mM glucose, 200 μM hydrogen peroxide (H₂O₂), and 50 μM sodium azide. Initially, the effect of these treatments on cell growth rate was examined, with each treatment significantly inhibiting growth rate. LDH and MTT assays were also used to successfully demonstrate that these treatments do not significantly increase cell lysis, but do significantly impair mitochondrial dehydrogenase activity. To confirm this mitochondria specific form of inhibition, DCFDA assay were used to investigate any increases in intracellular reactive oxygen species (ROS) generation. All three treatments resulted in significantly increased ROS generation, with greater ROS production occurring with a greater exposure time. Interestingly, when the protein levels of HSP60 and HSP70 were measured after 3 and 7 days of exposure of the HeLa cells to 100 mM glucose, 200 μM H₂O₂, and 50 μM sodium azide significant induction of these two molecular stress proteins were observed ranging from 2.43-5.08 fold compared to untreated control cells.

year: 2013

title: Dynamic mud deposition along the fluvial–tidal transition zone in the Waihou River, Aotearoa New Zealand

authors: La Croix, Andrew D.

abstract: The fluvial–tidal transition zone (FTT) is a critical interface where complex interactions between river flow, tides, and sedimentation shape geomorphic systems and influence the dynamics of aquatic environments. However, few previous studies have integrated real‐time hydrodynamic data with sedimentary deposits. In particular, the range of depositional conditions over which mud accumulates remains poorly constrained, and little is understood about how these deposits are preserved in the stratigraphic record. To address this knowledge gap, we examined co‐located hydrodynamic instrument data and sedimentary deposits from the lower Waihou River, Aotearoa New Zealand. Results reveal that “dynamic mud” events, including fluid mud and rapidly deposited mud, dominate the spatial and temporal record, with few “static mud” events in which mud is deposited through gravitational settling. We suggest that dynamic mud conditions with the potential for deposition may occur throughout the tidal cycle, although cyclic tidal successions are never fully preserved. Many of the trends in sedimentation observed in studies of larger systems are not present in this small muddy river system, indicating the significance of climatic and river‐flow characteristics on the sedimentary record. This work underscores the importance of studying systems of multiple sizes across diverse climatic regimes to establish holistic facies models to reconstruct geological history accurately.

text: Dynamic mud deposition along the fluvial–tidal transition zone in the Waihou River, Aotearoa New Zealand The fluvial–tidal transition zone (FTT) is a critical interface where complex interactions between river flow, tides, and sedimentation shape geomorphic systems and influence the dynamics of aquatic environments. However, few previous studies have integrated real‐time hydrodynamic data with sedimentary deposits. In particular, the range of depositional conditions over which mud accumulates remains poorly constrained, and little is understood about how these deposits are preserved in the stratigraphic record. To address this knowledge gap, we examined co‐located hydrodynamic instrument data and sedimentary deposits from the lower Waihou River, Aotearoa New Zealand. Results reveal that “dynamic mud” events, including fluid mud and rapidly deposited mud, dominate the spatial and temporal record, with few “static mud” events in which mud is deposited through gravitational settling. We suggest that dynamic mud conditions with the potential for deposition may occur throughout the tidal cycle, although cyclic tidal successions are never fully preserved. Many of the trends in sedimentation observed in studies of larger systems are not present in this small muddy river system, indicating the significance of climatic and river‐flow characteristics on the sedimentary record. This work underscores the importance of studying systems of multiple sizes across diverse climatic regimes to establish holistic facies models to reconstruct geological history accurately.

year: 2025

title: Ethnic disparities in breast cancer survival in New Zealand: which factors contribute?

authors: Tin Tin, Sandar

subjects: Breast cancer

abstract: Background: New Zealand has major ethnic disparities in breast cancer survival with Maori (indigenous people) and Pacific women (immigrants or descended from immigrants from Pacific Islands) faring much worse than other ethnic groups. This paper identified underlying factors and assessed their relative contribution to this risk differential. 
Methods: This study involved all women who were diagnosed with primary invasive breast cancer in two health regions, covering about 40% of the national population, between January 2000 and June 2014. Maori and Pacific patients were compared with other ethnic groups in terms of demographics, mode of diagnosis, disease factors and treatment factors. Cox regression modelling was performed with stepwise adjustments, and hazards of excess mortality from breast cancer for Maori and Pacific patients were assessed. 
Results: Of the 13,657 patients who were included in this analysis, 1281 (9.4%) were Maori, and 897 (6.6%) were Pacific women. Compared to other ethnic groups, they were younger, more likely to reside in deprived neighbourhoods and to have co-morbidities, and less likely to be diagnosed through screening and with early stage cancer, to be treated in a private care facility, to receive timely cancer treatment, and to receive breast conserving surgery. They had a higher risk of excess mortality from breast cancer (age and year of diagnosis adjusted hazard ratio: 1.76; 95% CI: 1.51-2.04 for Maori and 1.97; 95% CI: 1.67-2.32 for Pacific women), of which 75% and 99% respectively were explained by baseline differences. The most important contributor was late stage at diagnosis. Other contributors included neighbourhood deprivation, mode of diagnosis, type of health care facility where primary cancer treatment was undertaken and type of loco-regional therapy. 
Conclusions: Late diagnosis, deprivation and differential access to and quality of cancer care services were the key contributors to ethnic disparities in breast cancer survival in New Zealand. Our findings underscore the need for a greater equity focus along the breast cancer care pathway, with an emphasis on improving access to early diagnosis for Maori and Pacific women.

text: Ethnic disparities in breast cancer survival in New Zealand: which factors contribute? Background: New Zealand has major ethnic disparities in breast cancer survival with Maori (indigenous people) and Pacific women (immigrants or descended from immigrants from Pacific Islands) faring much worse than other ethnic groups. This paper identified underlying factors and assessed their relative contribution to this risk differential. 
Methods: This study involved all women who were diagnosed with primary invasive breast cancer in two health regions, covering about 40% of the national population, between January 2000 and June 2014. Maori and Pacific patients were compared with other ethnic groups in terms of demographics, mode of diagnosis, disease factors and treatment factors. Cox regression modelling was performed with stepwise adjustments, and hazards of excess mortality from breast cancer for Maori and Pacific patients were assessed. 
Results: Of the 13,657 patients who were included in this analysis, 1281 (9.4%) were Maori, and 897 (6.6%) were Pacific women. Compared to other ethnic groups, they were younger, more likely to reside in deprived neighbourhoods and to have co-morbidities, and less likely to be diagnosed through screening and with early stage cancer, to be treated in a private care facility, to receive timely cancer treatment, and to receive breast conserving surgery. They had a higher risk of excess mortality from breast cancer (age and year of diagnosis adjusted hazard ratio: 1.76; 95% CI: 1.51-2.04 for Maori and 1.97; 95% CI: 1.67-2.32 for Pacific women), of which 75% and 99% respectively were explained by baseline differences. The most important contributor was late stage at diagnosis. Other contributors included neighbourhood deprivation, mode of diagnosis, type of health care facility where primary cancer treatment was undertaken and type of loco-regional therapy. 
Conclusions: Late diagnosis, deprivation and differential access to and quality of cancer care services were the key contributors to ethnic disparities in breast cancer survival in New Zealand. Our findings underscore the need for a greater equity focus along the breast cancer care pathway, with an emphasis on improving access to early diagnosis for Maori and Pacific women.

year: 2018