Journal of Energy Bioscience 2025, Vol.16, No.1, 31-41 http://bioscipublisher.com/index.php/jeb 38 7.3 Implications for immune health and potential targets for enhancing NADPH in immunocompromised individuals If NADPH oxidase does not work properly, it will make the immune system very vulnerable. For example, in CGD patients, it can be seen that the failure of this enzyme leads to repeated infections and low immune function (El-Benna et al., 2005; Glennon-Alty et al., 2018). To improve this situation, scientists are trying some methods to increase the activity of NADPH oxidase or find other ways to make up for its deficiency. You can try to regulate the activation process of this enzyme. Methods such as phosphorylating p47phox or promoting its binding to PI(3)P may enhance the activity of the enzyme (El-Benna et al., 2009; Nunes et al., 2013). A deeper understanding of the role of reactive oxygen species in immune signaling and tissue regulation may also help us develop new treatments. These methods can effectively kill bacteria while reducing tissue damage (Edwards, 1996; Moghadam et al., 2021; Vermot et al., 2021). 8 Emerging Research and Future Directions 8.1 Recent advances in NADPH-related research Recent studies have made us more aware of the importance of NADPH in cellular metabolism and redox balance. Now, scientists have developed some new tools, such as genetically encoded biosensors. It can track NADPH levels in different regions of the cell in real time. This helps us understand how cells maintain the distribution of NADPH in different locations to avoid oxidative stress (Xiao et al., 2018). Other studies have found new enzymes that synthesize NADPH, which is very helpful for understanding its production and role in metabolic pathways (Pollak et al., 2007). At the same time, studies have once again emphasized the role of NADPH in clearing oxidative stress, such as helping to regenerate reduced glutathione or participating in other detoxification processes (Lee et al., 2002). A technology called fluorescence lifetime imaging microscopy (FLIM) can now distinguish NADH and NADPH in living cells. This allows us to study their respective metabolic functions from a new perspective (Blacker et al., 2014). 8.2 Potential applications of NADPH modulation in medicine, agriculture, and biotechnology Manipulating NADPH levels has great potential in medicine, agriculture, and biotechnology. In medicine, adjusting the metabolic pathways of NADPH may help treat diseases related to oxidative stress or metabolic disorders, such as diabetes, neurodegenerative diseases, and cancer (Ying, 2008; Blacker and Duchen, 2016). For example, increasing NADPH production or enhancing its utilization can enhance the ability of cells to resist oxidative damage and support tissue repair (Chan et al., 2009; Henríquez-Olguín et al., 2019). In agriculture, regulating the enzymes that produce NADPH in plants may also enhance the resistance of crops to environmental stresses such as heat and drought. This will not only help increase yields, but also make agriculture more sustainable (Corpas and Barroso, 2014; Corpas et al., 2020). In the field of biotechnology, optimizing the efficiency of NADPH-related reactions can help improve the biosynthetic capacity of industrial strains, such as producing biofuels and other valuable metabolites (Pollak et al., 2007). 8.3 Unresolved questions and future research needs Although we have made some progress, there are still many questions that need to be further studied. A key question is: How do cells adjust the distribution of NADPH under different physiological or pathological conditions? How do these changes help cells maintain redox balance? This is still unclear (Ying, 2008; Xiao et al., 2018). The connection between NADPH and other signaling pathways, such as hypoxia-inducible factor (HIF) or calcium signaling, also needs further investigation. There may be complex interactions between them, which will affect the cell's stress response and metabolism (Lee et al., 2002; Xiao et al., 2018). We also need to develop more advanced tools to measure or control NADPH levels in vivo. This will help us understand its dynamic changes at different time points and locations (Blacker et al., 2014). If we really use methods to regulate NADPH in clinical or agricultural applications in the future, we must also evaluate its side effects and long-term effects in advance to ensure that these methods are safe and effective (Chan et al., 2009; Henríquez-Olguín et al., 2019).
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