bims-mignad 2024-10-06 papers

Issue of 2024‒10‒06
five papers selected by
Melisa Emel Ermert, Amsterdam UMC

Aging Cell. 2024 Oct 01. e14326

Dysregulated nicotinamide adenine dinucleotide metabolome in patients hospitalized with COVID-19.

Rodrigo J Valderrábano, Benjamin Wipper, Karol Mateusz Pencina, Marie Migaud, Yili Valentine Shang, Nancy K Latham, Monty Montano, James M Cunningham, Lauren Wilson, Liming Peng, Yusnie Memish-Beleva, Avantika Bhargava, Pamela M Swain, Phoebe Lehman, Siva Lavu, David J Livingston, Shalender Bhasin.

Nicotinamide adenine dinucleotide (NAD+) depletion has been postulated as a contributor to the severity of COVID-19; however, no study has prospectively characterized NAD+ and its metabolites in relation to disease severity in patients with COVID-19. We measured NAD+ and its metabolites in 56 hospitalized patients with COVID-19 and in two control groups without COVID-19: (1) 31 age- and sex-matched adults with comorbidities, and (2) 30 adults without comorbidities. Blood NAD+ concentrations in COVID-19 group were only slightly lower than in the control groups (p < 0.05); however, plasma 1-methylnicotinamide concentrations were significantly higher in patients with COVID-19 (439.7 ng/mL, 95% CI: 234.0, 645.4 ng/mL) than in age- and sex-matched controls (44.5 ng/mL, 95% CI: 15.6, 73.4) and in healthy controls (18.1 ng/mL, 95% CI 15.4, 20.8; p < 0.001 for each comparison). Plasma nicotinamide concentrations were also higher in COVID-19 group and in controls with comorbidities than in healthy control group. Plasma concentrations of 2-methyl-2-pyridone-5-carboxamide (2-PY), but not NAD+, were significantly associated with increased risk of death (HR = 3.65; 95% CI 1.09, 12.2; p = 0.036) and escalation in level of care (HR = 2.90, 95% CI 1.01, 8.38, p = 0.049). RNAseq and RTqPCR analyses of PBMC mRNA found upregulation of multiple genes involved in NAD+ synthesis as well as degradation, and dysregulation of NAD+-dependent processes including immune response, DNA repair, metabolism, apoptosis/autophagy, redox reactions, and mitochondrial function. Blood NAD+ concentrations are modestly reduced in COVID-19; however, NAD+ turnover is substantially increased with upregulation of genes involved in both NAD+ biosynthesis and degradation, supporting the rationale for NAD+ augmentation to attenuate disease severity.

Keywords: 1‐methylnicotinamide; 2PY; NAD+ augmentation in COVID‐19; NAD+ metabolites; NAD+ turnover; SARS‐CoV‐2 infection; nicotinamide

DOI: https://doi.org/10.1111/acel.14326

MedComm (2020). 2024 Oct;5(10): e727

Nicotinamide mononucleotide supplementation rescues mitochondrial and energy metabolism functions and ameliorates inflammatory states in the ovaries of aging mice.

Jinghui Liang, Feiling Huang, Xueyu Hao, Peng Zhang, Rong Chen.

Noninvasive pharmacological strategies like nicotinamide mononucleotide (NMN) supplementation can effectively address age-related ovarian infertility by maintaining or enhancing oocyte quality and quantity. This study revealed that ovarian nicotinamide adenine dinucleotide levels decline with age, but NMN administration significantly restores these levels, preventing ovarian atrophy and enhancing the quality and quantity of ovulated oocytes. Improvements in serum hormone secretion and antioxidant factors, along with decreased expression of proinflammatory factors, were observed. Additionally, a significant increase in the number of ovarian follicles in aging individuals was noted. Scanning electron microscopy data indicated that NMN significantly alters the density and morphology of lipid droplets and mitochondria in granulosa cells, suggesting potential targets and mechanisms. Transcriptomic analysis and validation experiments collectively suggested that the beneficial effects of NMN on aging ovaries are mediated through enhanced mitochondrial function, improved energy metabolism, and reduced inflammation levels. Our results suggest that NMN supplementation could improve the health status of aging ovaries and enhance ovarian reserve, offering new insights into addressing fertility challenges in older women through assisted reproductive technology.

Keywords: infertility; nicotinamide adenine dinucleotide (NAD+); nicotinamide mononucleotide; ovarian aging

DOI: https://doi.org/10.1002/mco2.727

Adv Healthc Mater. 2024 Sep 29. e2402785

Advancements in NADH Oxidase Nanozymes: Bridging Nanotechnology and Biomedical Applications.

Dan Li, Juyang He, Guanyu Ding, Yan Xin, Fan Feng, Shuaining Ma, Lu Lin, Erkang Wang, Jin Wang.

Nicotinamide adenine dinucleotide (NADH) oxidase (NOX) is key in converting NADH to NAD+, crucial for various biochemical pathways. However, natural NOXs are costly and unstable. NOX nanozymes offer a promising alternative with potential applications in bio-sensing, antibacterial treatments, anti-aging, and anticancer therapies. This review provides a comprehensive overview of the types, functional mechanisms, biomedical applications, and future research perspectives of NOX nanozymes. It also addresses the primary challenges and future directions in the research and development of NOX nanozymes, underscoring the critical need for continued investigation in this promising area. These challenges include optimizing the catalytic efficiency, ensuring biocompatibility, and achieving targeted delivery and controlled activity within biological systems. Additionally, the exploration of novel materials and hybrid structures holds great potential for enhancing the functional capabilities of NOX nanozymes. Future research directions can involve integrating advanced computational modeling with experimental techniques to better understand the underlying mechanisms and to design more effective nanozyme candidates. Collaborative efforts across disciplines such as nanotechnology, biochemistry, and medicine will be essential to unlock the full potential of NOX nanozymes in future biomedical applications.

Keywords: NADH oxidase nanozyme; antibacterial treatment; anticancer therapy; anti‐aging; biosensor

DOI: https://doi.org/10.1002/adhm.202402785

Brain Sci. 2024 Sep 05. pii: 899. [Epub ahead of print]14(9):

Integrating Mitochondrial Biology into Innovative Cell Therapies for Neurodegenerative Diseases.

Adaleiz Ore, James M Angelastro, Cecilia Giulivi.

The role of mitochondria in neurodegenerative diseases is crucial, and recent developments have highlighted its significance in cell therapy. Mitochondrial dysfunction has been implicated in various neurodegenerative disorders, including Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and Huntington's diseases. Understanding the impact of mitochondrial biology on these conditions can provide valuable insights for developing targeted cell therapies. This mini-review refocuses on mitochondria and emphasizes the potential of therapies leveraging mesenchymal stem cells, embryonic stem cells, induced pluripotent stem cells, stem cell-derived secretions, and extracellular vesicles. Mesenchymal stem cell-mediated mitochondria transfer is highlighted for restoring mitochondrial health in cells with dysfunctional mitochondria. Additionally, attention is paid to gene-editing techniques such as mito-CRISPR, mitoTALENs, mito-ZNFs, and DdCBEs to ensure the safety and efficacy of stem cell treatments. Challenges and future directions are also discussed, including the possible tumorigenic effects of stem cells, off-target effects, disease targeting, immune rejection, and ethical issues.

Keywords: cell therapy; ethical concerns; exosomes; extracellular vesicles; mitochondrial dysfunction; mitochondrial medicine; neurodegenerative diseases; stem cells

DOI: https://doi.org/10.3390/brainsci14090899

Theranostics. 2024 ;14(15): 5826-5852

Ferroptosis at the nexus of metabolism and metabolic diseases.

Shuangwen Li, Guixiang Zhang, Jiankun Hu, Yan Tian, Xianghui Fu.

Ferroptosis, an iron-dependent form of regulated cell death, is emerging as a crucial regulator of human physiology and pathology. Increasing evidence showcases a reciprocal relationship between ferroptosis and dysregulated metabolism, propagating a pathogenic vicious cycle that exacerbates pathology and human diseases, particularly metabolic disorders. Consequently, there is a rapidly growing interest in developing ferroptosis-based therapeutics. Therefore, a comprehensive understanding of the intricate interplay between ferroptosis and metabolism could provide an invaluable resource for mechanistic insight and therapeutic development. In this review, we summarize the important metabolic substances and associated pathways in ferroptosis initiation and progression, outline the cascade responses of ferroptosis in disease development, overview the roles and mechanisms of ferroptosis in metabolic diseases, introduce the methods for ferroptosis detection, and discuss the therapeutic perspectives of ferroptosis, which collectively aim to illustrate a comprehensive view of ferroptosis in basic, translational, and clinical science.

Keywords: Ferroptosis cascade responses; Ferroptosis-related therapeutics; Glucose catabolism; Lipid peroxidation; Redox metabolism

DOI: https://doi.org/10.7150/thno.100080