DNA interstrand cross-links (ICLs) are essential for the antitumor activity of chloroethylnitrosoureas (CENUs). Commonly, CENUs resistance is mainly considered to be associated with O6-methylguanine-DNA methyltransferase (MGMT) within tumors. Bypassing the MGMT-mediated resistance, to our knowledge, herein, we first utilized a novel glycolytic inhibitor, 3-bromopyruvate (3-BrPA), to increase the cytotoxic effects of l,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to human glioma cells based on the hypothesis that blocking energy metabolism renders tumor cells more sensitive to chemotherapy. We found 3-BrPA significantly increased the cell killing by BCNU in human glioma SF763 and SF126 cell lines. Significantly decreased levels of extracellular lactate, cellular ATP and glutathione (GSH) were observed after 3-BrPA treatment, and the effects were more remarkable with 3-BrPA in combination with BCNU. Considering that the role of ATP and GSH in drug efflux, DNA damage repair and drug inactivation, we determined the effect of 3-BrPA on the formation of dG-dC ICLs induced by BCNU using stable isotope dilution high-performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). As expected, the levels of lethal dG-dC ICLs induced by BCNU were obviously enhanced after 3-BrPA pretreatment. Based on these results, 3-BrPA and related glycolytic inhibitors may be promising to enhance the cell killing effect and reverse the clinical chemoresistance of CENUs and related antitumor agents. Within the domain of food consumption, we explore the antecedents and consequences of "guilty displeasures," or experiences that consumers should enjoy, but do not. Food is an emotionally charged stimulus, with consumption leading to both positive (e.g., joy) and negative (e.g., guilt) emotions. Individuals who are high in dietary restraint are particularly susceptible to experiencing negative emotions given their heightened state of arousal in the presence of indulgent food. We show that these negative emotions arise even when individuals simply imagine the food. Across one pilot study and three experiments, we provide evidence that restrained eaters actively dampen their enjoyment of indulgences (i.e., guilty displeasures). We manipulate guilt using imagery type, with outcome imagery leading to greater guilt than process imagery (study 1). We also demonstrate that individuals high, compared to low, in dietary restraint dampen their savoring of even a hypothetical indulgence when guilt is evoked (study 2). Finally, we show these effects within the context of actual food consumption (study 3). Our exploration shows that merely anticipating an indulgence can elicit guilt among consumers high in dietary restraint, thus resulting in the dampening of enjoyment during a subsequent consumption experience. The consumption of animal products, especially meat, contributes heavily to climate change. Despite an increased number of individuals reducing their meat consumption, little research has explored flexitarianism. The objective of this study was to explore the motivations, barriers, and strategies for reduced meat consumption. The qualitative study, utilizing six focus groups in New Zealand, explores the cognitive, affective, and cultural components of meat reduction through the examination of the different stages of the family lifecycle. The research finds significant differences in motivations for meat reduction between young adults, families, and retirees, with health, environmental and cost important factors but to different degrees. However, all continue to eat meat due to cravings, taste and nutrition beliefs. Strategies for substitution are similar for young adults and families but differ from retirees, with the former populations exhibiting greater creativity and exploration, not seeing meat reduction as 'meat replacement' but instead as a recreation of the main meal. The barriers to meat reduction are similar across the family lifecycle with a lack of information and cultural, media, and institutional discourse large inhibitors to reduction. Yet, social and cultural factors also encourage individuals to reflect on their meat consumption and social connections (including social media) provide accessible and persuasive messaging for meat reduction. Consequently, public education and social marketing campaigns need to be implemented to provide information and recipes, and such information should be in varied formats to appeal to different consumer segments. Meat consumption has become a contentious issue among the Swiss population. https://www.selleckchem.com/products/sodium-l-lactate.html The emotional character of the debates surrounding the necessity for a change of habits, namely a reduction in consumption and a shift in the kind of meat we eat, reveals its particular place in our societies as a symbolic food with roots in our affective economies, as involved in the creation of a shared culture and national identity, and as a political object used to defend different views. To date, research in sustainable consumption has given **** attention to environmental- and animal-friendly groups and their practices. However, certain interest groups have been voicing the right to meat, or promoting alternative forms of meat consumption. In this paper, we seek to understand the affective dimension of 'no', 'low' and 'pro' meat consumption initiatives in the Swiss context. Based on a qualitative study and an understanding of emotions as part of social practices, we draw out what affects and related moralities are being mobilized by prescribers and how they are picked up in practice. By doing so, we contribute to further understanding the emotions and moral registers linked to different approaches to meat (non)consumption, their role in promoting certain practices over others, as well as the dynamics that make reducing meat consumption so controversial. We conclude by discussing the need to take emotions and related moralities seriously as a crucial step towards understanding opportunities for 'healthy and sustainable' food practices. Nuclear receptors (NRs) rapidly activate/repress gene expression to detour immune responses and allow tissue adaptation to constant environmental changes. However, the effect of combined NRs in the immune system is often unclear due to the lack of reliable experimental models that recapitulate the complex interaction between NRs in vivo. Here, we used the zebrafish to investigate the immunological outcome of combining the activation of retinoic acid receptor (RAR), liver X receptor (LXR) and the cytoplasmic sensor aryl hydrocarbon receptor (AHR). Although simultaneous activation did not affect the expression of respective bona-fide target genes, RAR-induced il17a/f3 was antagonized by LXR and AHR, whereas il22 was antagonized by AHR but not LXR. In addition, RA decreased il10 expression, which was further decreased by LXR activation. Thus, using combinatorial NR activation in zebrafish larvae, we show that LXR antagonizes the expression of selected RA-induced cytokines and provide a strategy to tailor the cytokine milieu.
DNA interstrand cross-links (ICLs) are essential for the antitumor activity of chloroethylnitrosoureas (CENUs). Commonly, CENUs resistance is mainly considered to be associated with O6-methylguanine-DNA methyltransferase (MGMT) within tumors. Bypassing the MGMT-mediated resistance, to our knowledge, herein, we first utilized a novel glycolytic inhibitor, 3-bromopyruvate (3-BrPA), to increase the cytotoxic effects of l,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to human glioma cells based on the hypothesis that blocking energy metabolism renders tumor cells more sensitive to chemotherapy. We found 3-BrPA significantly increased the cell killing by BCNU in human glioma SF763 and SF126 cell lines. Significantly decreased levels of extracellular lactate, cellular ATP and glutathione (GSH) were observed after 3-BrPA treatment, and the effects were more remarkable with 3-BrPA in combination with BCNU. Considering that the role of ATP and GSH in drug efflux, DNA damage repair and drug inactivation, we determined the effect of 3-BrPA on the formation of dG-dC ICLs induced by BCNU using stable isotope dilution high-performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). As expected, the levels of lethal dG-dC ICLs induced by BCNU were obviously enhanced after 3-BrPA pretreatment. Based on these results, 3-BrPA and related glycolytic inhibitors may be promising to enhance the cell killing effect and reverse the clinical chemoresistance of CENUs and related antitumor agents. Within the domain of food consumption, we explore the antecedents and consequences of "guilty displeasures," or experiences that consumers should enjoy, but do not. Food is an emotionally charged stimulus, with consumption leading to both positive (e.g., joy) and negative (e.g., guilt) emotions. Individuals who are high in dietary restraint are particularly susceptible to experiencing negative emotions given their heightened state of arousal in the presence of indulgent food. We show that these negative emotions arise even when individuals simply imagine the food. Across one pilot study and three experiments, we provide evidence that restrained eaters actively dampen their enjoyment of indulgences (i.e., guilty displeasures). We manipulate guilt using imagery type, with outcome imagery leading to greater guilt than process imagery (study 1). We also demonstrate that individuals high, compared to low, in dietary restraint dampen their savoring of even a hypothetical indulgence when guilt is evoked (study 2). Finally, we show these effects within the context of actual food consumption (study 3). Our exploration shows that merely anticipating an indulgence can elicit guilt among consumers high in dietary restraint, thus resulting in the dampening of enjoyment during a subsequent consumption experience. The consumption of animal products, especially meat, contributes heavily to climate change. Despite an increased number of individuals reducing their meat consumption, little research has explored flexitarianism. The objective of this study was to explore the motivations, barriers, and strategies for reduced meat consumption. The qualitative study, utilizing six focus groups in New Zealand, explores the cognitive, affective, and cultural components of meat reduction through the examination of the different stages of the family lifecycle. The research finds significant differences in motivations for meat reduction between young adults, families, and retirees, with health, environmental and cost important factors but to different degrees. However, all continue to eat meat due to cravings, taste and nutrition beliefs. Strategies for substitution are similar for young adults and families but differ from retirees, with the former populations exhibiting greater creativity and exploration, not seeing meat reduction as 'meat replacement' but instead as a recreation of the main meal. The barriers to meat reduction are similar across the family lifecycle with a lack of information and cultural, media, and institutional discourse large inhibitors to reduction. Yet, social and cultural factors also encourage individuals to reflect on their meat consumption and social connections (including social media) provide accessible and persuasive messaging for meat reduction. Consequently, public education and social marketing campaigns need to be implemented to provide information and recipes, and such information should be in varied formats to appeal to different consumer segments. Meat consumption has become a contentious issue among the Swiss population. https://www.selleckchem.com/products/sodium-l-lactate.html The emotional character of the debates surrounding the necessity for a change of habits, namely a reduction in consumption and a shift in the kind of meat we eat, reveals its particular place in our societies as a symbolic food with roots in our affective economies, as involved in the creation of a shared culture and national identity, and as a political object used to defend different views. To date, research in sustainable consumption has given much attention to environmental- and animal-friendly groups and their practices. However, certain interest groups have been voicing the right to meat, or promoting alternative forms of meat consumption. In this paper, we seek to understand the affective dimension of 'no', 'low' and 'pro' meat consumption initiatives in the Swiss context. Based on a qualitative study and an understanding of emotions as part of social practices, we draw out what affects and related moralities are being mobilized by prescribers and how they are picked up in practice. By doing so, we contribute to further understanding the emotions and moral registers linked to different approaches to meat (non)consumption, their role in promoting certain practices over others, as well as the dynamics that make reducing meat consumption so controversial. We conclude by discussing the need to take emotions and related moralities seriously as a crucial step towards understanding opportunities for 'healthy and sustainable' food practices. Nuclear receptors (NRs) rapidly activate/repress gene expression to detour immune responses and allow tissue adaptation to constant environmental changes. However, the effect of combined NRs in the immune system is often unclear due to the lack of reliable experimental models that recapitulate the complex interaction between NRs in vivo. Here, we used the zebrafish to investigate the immunological outcome of combining the activation of retinoic acid receptor (RAR), liver X receptor (LXR) and the cytoplasmic sensor aryl hydrocarbon receptor (AHR). Although simultaneous activation did not affect the expression of respective bona-fide target genes, RAR-induced il17a/f3 was antagonized by LXR and AHR, whereas il22 was antagonized by AHR but not LXR. In addition, RA decreased il10 expression, which was further decreased by LXR activation. Thus, using combinatorial NR activation in zebrafish larvae, we show that LXR antagonizes the expression of selected RA-induced cytokines and provide a strategy to tailor the cytokine milieu.
0 Commenti
0 condivisioni
110 Views
0 Anteprima
