title: Effects of metformin on human monocytic THP-1 cells - Implications for type 2 diabetes mellitus

authors: Tsuei, An-Chi

subjects: Metformin

abstract: Metformin is an anti-hyperglycaemic agent widely prescribed for type 2 diabetes (T2D). Despite decades of clinical use, its exact pharmacological mechanism(s) is yet to be definitively determined. Accumulative data have shown its mild inhibitory effect on the complex 1 of the mitochondrial respiratory chain, which is thought to contribute to its anti-hyperglycaemic effect. Metformin is also thought to have a protective effect on cardiovascular disease (CVD), the most common complication in T2D. It is widely accepted that T2D is an inflammatory state thus it is not surprising that T2D patients have 2-4 times higher risk in developing CVD. Furthermore, the pathology of T2D has been proposed to involve dysfunctioning mitochondria, the organelle of energy sensing and production. The use of metformin, a mitochondria inhibitor, in cells under mitochondrial stress led us to speculate the physiological responses that ensue.
To understand metformin‟s mode of action and its involvement in inflammation processes the human monocytic leukemia THP-1 cells were used in this study. Since studies of metformin on this cell type is scarce if not non-existence the first task was to determine its cytoxicity in this cell line. Next the mRNA and protein expressions of heat shock protein 60 (Hsp60), a mitochondrial stress marker, was determined in metformin-treated THP-1 cells. Further, various cell types have shown surface expressed Hsp60 under stress conditions. Thus the study here attempted to optimise the detection of surface Hsp60 in THP-1 cells, as human Hsp60 has been shown to induce innate immune response. Localisation of Hsp60 on the cell surface in metformin-treated cells may exacerbate the already-inflammed state of T2D. Lastly, metformin‟s effect on PMA-stimulated monocyte differentiation was determined by the mRNA expression of CD14, a surface receptor on macrophages.
The results here agreed with published data that metformin at therapeutic concentrations are not cytotoxic and is a mild inhibitor of mitochondrial respiration. We also provide evidence that metformin up-regulated the mitochondria stress protein, Hsp60, in a time- and dose-dependent manner. In addition, live cell Hsp60 immunocytochemistry proved to be a promising method for surface Hsp60 detection in THP-1 cells. Finally, at the therapeutic concentration metformin caused a significant up-regulation in cd14 expression, which contradicts with much acclaimed protective effect of metformin in the literature.

text: Effects of metformin on human monocytic THP-1 cells - Implications for type 2 diabetes mellitus Metformin is an anti-hyperglycaemic agent widely prescribed for type 2 diabetes (T2D). Despite decades of clinical use, its exact pharmacological mechanism(s) is yet to be definitively determined. Accumulative data have shown its mild inhibitory effect on the complex 1 of the mitochondrial respiratory chain, which is thought to contribute to its anti-hyperglycaemic effect. Metformin is also thought to have a protective effect on cardiovascular disease (CVD), the most common complication in T2D. It is widely accepted that T2D is an inflammatory state thus it is not surprising that T2D patients have 2-4 times higher risk in developing CVD. Furthermore, the pathology of T2D has been proposed to involve dysfunctioning mitochondria, the organelle of energy sensing and production. The use of metformin, a mitochondria inhibitor, in cells under mitochondrial stress led us to speculate the physiological responses that ensue.
To understand metformin‟s mode of action and its involvement in inflammation processes the human monocytic leukemia THP-1 cells were used in this study. Since studies of metformin on this cell type is scarce if not non-existence the first task was to determine its cytoxicity in this cell line. Next the mRNA and protein expressions of heat shock protein 60 (Hsp60), a mitochondrial stress marker, was determined in metformin-treated THP-1 cells. Further, various cell types have shown surface expressed Hsp60 under stress conditions. Thus the study here attempted to optimise the detection of surface Hsp60 in THP-1 cells, as human Hsp60 has been shown to induce innate immune response. Localisation of Hsp60 on the cell surface in metformin-treated cells may exacerbate the already-inflammed state of T2D. Lastly, metformin‟s effect on PMA-stimulated monocyte differentiation was determined by the mRNA expression of CD14, a surface receptor on macrophages.
The results here agreed with published data that metformin at therapeutic concentrations are not cytotoxic and is a mild inhibitor of mitochondrial respiration. We also provide evidence that metformin up-regulated the mitochondria stress protein, Hsp60, in a time- and dose-dependent manner. In addition, live cell Hsp60 immunocytochemistry proved to be a promising method for surface Hsp60 detection in THP-1 cells. Finally, at the therapeutic concentration metformin caused a significant up-regulation in cd14 expression, which contradicts with much acclaimed protective effect of metformin in the literature.

year: 2010

title: The Impacts of Social Media and Electronic Mediating: Improving Educational Outcomes for Saudi Women within an Electronic Social Networking Environment

authors: Alkahtani, Norah

subjects: Social Networking

abstract: This dissertation reports on a study about the effects of social media, such as social networks used by female university students in the context of a gender segregated system in Saudi Arabia. 

The result clearly reflects that social media has a positive effect on the collaborations of students, as they are able to keep their cultural and religious values without physically intermingling with the opposite sex, which is a requirement of religion and culture.

This research was carried out through two stages. The first stage was an exploratory study carried out for post graduate Saudi students at The University of Waikato. Students from both genders were granted scholarships from the King of Saudi Arabia, “King Abdullah”. They have had the experience of studying within two different cultures, in Saudi Arabia and New Zealand. They have had good experiences within the mixed gender environment at The University of Waikato.  

The second stage was action research, to diagnose the importance of social networks in the education system for Saudi females at Saudi universities. The segregation between genders in Saudi Arabia is a big issue at universities but with the appearance of social networks such as Facebook genders can interact easily without being physically in the same place. 

The action research took place through three cycles at three different universities; King Saud University and Imam University, which are public universities and the last cycle in private Universities, in Riyadh. 

The results collecting data revealed that electronic social networks could help promote collaboration between both genders in Saudi Arabia. Both genders felt more comfortable dealing with the opposite gender under the umbrella of education without harming their culture or religion.

text: The Impacts of Social Media and Electronic Mediating: Improving Educational Outcomes for Saudi Women within an Electronic Social Networking Environment This dissertation reports on a study about the effects of social media, such as social networks used by female university students in the context of a gender segregated system in Saudi Arabia. 

The result clearly reflects that social media has a positive effect on the collaborations of students, as they are able to keep their cultural and religious values without physically intermingling with the opposite sex, which is a requirement of religion and culture.

This research was carried out through two stages. The first stage was an exploratory study carried out for post graduate Saudi students at The University of Waikato. Students from both genders were granted scholarships from the King of Saudi Arabia, “King Abdullah”. They have had the experience of studying within two different cultures, in Saudi Arabia and New Zealand. They have had good experiences within the mixed gender environment at The University of Waikato.  

The second stage was action research, to diagnose the importance of social networks in the education system for Saudi females at Saudi universities. The segregation between genders in Saudi Arabia is a big issue at universities but with the appearance of social networks such as Facebook genders can interact easily without being physically in the same place. 

The action research took place through three cycles at three different universities; King Saud University and Imam University, which are public universities and the last cycle in private Universities, in Riyadh. 

The results collecting data revealed that electronic social networks could help promote collaboration between both genders in Saudi Arabia. Both genders felt more comfortable dealing with the opposite gender under the umbrella of education without harming their culture or religion.

year: 2012

title: Heritage-making in Aotearoa planning: Unsettling norms in contested urban space

authors: Hill, Carolyn Joy

subjects: Authorised heritage discourse

abstract: Heritage is currently a high-profile and often contentious topic in urban environments. As cities face growing challenges of climate change, intensification needs and cultural contestation, state-mandated heritage continues to have a significant influence on how cities are perceived, whose pasts are remembered, and what future change can be. However, this is being increasingly tested as urban pressures bring questions of who has a right to the city to the fore. 
Situated within the field of critical heritage studies, this thesis critically examines how heritage is officially “made” in the cities of Aotearoa New Zealand, and how emerging views and values may reshape these established norms for more spatially and culturally just futures. Focused on urban locations within the so-called “CANZUS” states (Canada, Australia, New Zealand and the United States of America (USA)), the thesis centres on statutory heritage – the objects and places that are identified and managed within state-mandated planning systems that create dominant assumptions about what is worthy of protection. As such, its contribution is at the intersection of heritage and planning as it critically queries heritage’s future legacy claims and considers what other legacies may be imagined. 
The thesis includes four key enquiries. First, it explores the history of state-led heritage-making in Aotearoa, focusing on the city of Tāmaki Makaurau / Auckland. It examines the tension between contemporary urban intensification priorities and heritage / special character regulation, critiquing the narrative of heritage as a “public good” given its entanglement with spatial and cultural inequity. Second, it studies three cases of urban heritage protest across Australia, Aotearoa and the USA. These cases expose the continued inadequacy of statutory heritage-making for Indigenous and emerging aspirations, as normative approaches are embedded not only by the heritage sector itself but by the planning and legislation systems that structure its mandate. 
Third, the thesis explores the current thinking of those shaping and working within heritage’s statutory framing across Aotearoa. It finds that heritage policy leaders are cognisant of, and concerned to change, heritage’s entrenched Eurocentricity, expert dominance and material orientation, but that shifting established practice remains a multi-dimensional challenge. Finally, it investigates the perspectives of young emerging planners in the city of Kirikiriroa / Hamilton, which again foregrounds the obstacles to displacing systemic norms but also highlights planning policy’s significant potential to shape different heritage futures. 
This thesis has important implications both for Aotearoa’s urban environments and for CANZUS cities more broadly. Grounded in contemporary real-world examples, it not only exposes heritage’s imbrication with issues of urban inequity but its deeper role in maintaining settler state security, making “home” on Indigenous land. It finds that unpicking this legacy will involve more than adding the heritages of “others” into the existing canon. Rather, deeper reconsideration of heritage’s societal purpose as part of Indigenous, multi-storied and dynamic cities is required. Finally, it highlights the central role for planning in transforming the heritage field, both through statutory policy reform and through integration with broader urban objectives. However, planners will need to be better equipped for critical engagement with heritage if they are to creatively support more inclusive, democratic and malleable alternatives.

text: Heritage-making in Aotearoa planning: Unsettling norms in contested urban space Heritage is currently a high-profile and often contentious topic in urban environments. As cities face growing challenges of climate change, intensification needs and cultural contestation, state-mandated heritage continues to have a significant influence on how cities are perceived, whose pasts are remembered, and what future change can be. However, this is being increasingly tested as urban pressures bring questions of who has a right to the city to the fore. 
Situated within the field of critical heritage studies, this thesis critically examines how heritage is officially “made” in the cities of Aotearoa New Zealand, and how emerging views and values may reshape these established norms for more spatially and culturally just futures. Focused on urban locations within the so-called “CANZUS” states (Canada, Australia, New Zealand and the United States of America (USA)), the thesis centres on statutory heritage – the objects and places that are identified and managed within state-mandated planning systems that create dominant assumptions about what is worthy of protection. As such, its contribution is at the intersection of heritage and planning as it critically queries heritage’s future legacy claims and considers what other legacies may be imagined. 
The thesis includes four key enquiries. First, it explores the history of state-led heritage-making in Aotearoa, focusing on the city of Tāmaki Makaurau / Auckland. It examines the tension between contemporary urban intensification priorities and heritage / special character regulation, critiquing the narrative of heritage as a “public good” given its entanglement with spatial and cultural inequity. Second, it studies three cases of urban heritage protest across Australia, Aotearoa and the USA. These cases expose the continued inadequacy of statutory heritage-making for Indigenous and emerging aspirations, as normative approaches are embedded not only by the heritage sector itself but by the planning and legislation systems that structure its mandate. 
Third, the thesis explores the current thinking of those shaping and working within heritage’s statutory framing across Aotearoa. It finds that heritage policy leaders are cognisant of, and concerned to change, heritage’s entrenched Eurocentricity, expert dominance and material orientation, but that shifting established practice remains a multi-dimensional challenge. Finally, it investigates the perspectives of young emerging planners in the city of Kirikiriroa / Hamilton, which again foregrounds the obstacles to displacing systemic norms but also highlights planning policy’s significant potential to shape different heritage futures. 
This thesis has important implications both for Aotearoa’s urban environments and for CANZUS cities more broadly. Grounded in contemporary real-world examples, it not only exposes heritage’s imbrication with issues of urban inequity but its deeper role in maintaining settler state security, making “home” on Indigenous land. It finds that unpicking this legacy will involve more than adding the heritages of “others” into the existing canon. Rather, deeper reconsideration of heritage’s societal purpose as part of Indigenous, multi-storied and dynamic cities is required. Finally, it highlights the central role for planning in transforming the heritage field, both through statutory policy reform and through integration with broader urban objectives. However, planners will need to be better equipped for critical engagement with heritage if they are to creatively support more inclusive, democratic and malleable alternatives.

year: 2024-12-16