Nicotinamide Efficiently Suppresses Porcine Epidemic Diarrhea Virus and Porcine Deltacoronavirus Replication DOI Creative Commons
Mingxia Li, Liping Zhang, Pan Li

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(7), P. 1591 - 1591

Published: July 21, 2023

Porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV), members of the genus Coronavirus, mainly cause acute diarrhea, vomiting dehydration in piglets, thus lead to serious economic losses. In this study, we investigated effects nicotinamide (NAM) on PEDV PDCoV replication found that NAM treatment significantly inhibited reproduction. Moreover, plays an important role processes. primarily RNA protein synthesis rather than other Furthermore, discovered likely inhibits by downregulating expression transcription factors through activation ERK1/2/MAPK pathway. Overall, study is first suggest might be not only antiviral factor for swine intestinal coronavirus, but also a potential candidate evaluated context human animal coronaviruses.

Language: Английский

β-Nicotinamide mononucleotide activates NAD+/SIRT1 pathway and attenuates inflammatory and oxidative responses in the hippocampus regions of septic mice DOI Creative Commons

Hui-ru Li,

Qiang Liu, Cheng‐long Zhu

et al.

Redox Biology, Journal Year: 2023, Volume and Issue: 63, P. 102745 - 102745

Published: May 13, 2023

Sepsis-associated encephalopathy (SAE) is one of the common serious complications in sepsis, and pathogenesis SAE remains unclear. Sirtuin 1 (SIRT1) has been reported to be downregulated hippocampus SIRT1 agonists can attenuated cognitive dysfunction septic mice. Nicotinamide adenine dinucleotide (NAD+) a key substrate maintain deacetylation activity SIRT1. As an intermediate NAD+, β-Nicotinamide Mononucleotide (NMN) promising treating neurodegenerative diseases cerebral ischemic injury. Thus we sought investigate potential role NMN treatment. The model was established by cecal ligation puncture (CLP) vivo, neuroinflammation with LPS-treated BV-2 cells vitro. Memory impairment assessed Morris water maze fear conditioning tests. result, levels PGC-1α were significantly reduced mice, while acetylation total lysine, phosphorylation P38 P65 enhanced. All these changes induced sepsis inverted NMN. Treating resulted improved behavior performance tests maze. Apoptosis, inflammatory oxidative responses mice after administration. These protective effect against memory dysfunction, injuries reversed inhibitor, EX-527. Similarly, LPS-induced activation NMN, EX-527 or knockdown could reverse such In conclusion, sepsis-induced region NAD+/SIRT1 pathway might involved mechanisms effect.

Language: Английский

Citations

52
Aggregation-Induced Emission Luminogen: Role in Biopsy for Precision Medicine DOI Creative Commons
Yanhong Duo, Lei Han, Yaoqiang Yang

et al.

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(20), P. 11242 - 11347

Published: Oct. 9, 2024

Biopsy, including tissue and liquid biopsy, offers comprehensive real-time physiological pathological information for disease detection, diagnosis, monitoring. Fluorescent probes are frequently selected to obtain adequate on processes in a rapid minimally invasive manner based their advantages biopsy. However, conventional fluorescent have been found show aggregation-caused quenching (ACQ) properties, impeding greater progresses this area. Since the discovery of aggregation-induced emission luminogen (AIEgen) promoted advancements molecular bionanomaterials owing unique high quantum yield (QY) signal-to-noise ratio (SNR),

Language: Английский

Citations

18
Herpes Simplex Virus 1-Induced Ferroptosis Contributes to Viral Encephalitis DOI Creative Commons

Xi-Qiu Xu,

Tongran Xu,

Wenting Ji

et al.

mBio, Journal Year: 2022, Volume and Issue: 14(1)

Published: Dec. 12, 2022

Herpes simplex virus 1 (HSV-1) is a DNA belonging to the family Herpesviridae. HSV-1 infection causes severe neurological disease in central nervous system (CNS), including encephalitis. Ferroptosis nonapoptotic form of programmed cell death that contributes different inflammatory diseases. However, whether induces ferroptosis CNS and role viral pathogenesis remain unclear. Here, we demonstrate ferroptosis, as hallmarks Fe2+ overload, reactive oxygen species (ROS) accumulation, glutathione (GSH) depletion, lipid peroxidation, mitochondrion shrinkage, are observed HSV-1-infected cultured human astrocytes, microglia cells, murine brains. Moreover, enhances E3 ubiquitin ligase Keap1 (Kelch-like ECH-related protein 1)-mediated ubiquitination degradation nuclear factor E2-related 2 (Nrf2), transcription regulates expression antioxidative genes, thereby disturbing cellular redox homeostasis promoting ferroptosis. Furthermore, HSV-1-induced tightly associated with process encephalitis mouse model, ferroptosis-activated upregulation prostaglandin-endoperoxide synthase (PTGS2) prostaglandin E2 (PGE2) plays an important HSV-1-caused inflammation Importantly, inhibition by inhibitor or proteasome suppress Nrf2 effectively alleviated Together, our findings interaction between provide novel insights into IMPORTANCE In current study, ROS GSH all which brains infected HSV-1. Keap1-dependent degradation, results substantial reductions levels antiferroptotic genes downstream Nrf2, PTGS2 PGE2 either alleviates neuro-damage mice. Overall, uncover shed light on physiological impacts encephalitis, promising therapeutic strategy treat this infectious worldwide distribution.

Language: Английский

Citations

48
Metabolomics in drug research and development: The recent advances in technologies and applications DOI Creative Commons
Huanhuan Pang, Zeping Hu

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 13(8), P. 3238 - 3251

Published: May 23, 2023

Emerging evidence has demonstrated the vital role of metabolism in various diseases or disorders. Metabolomics provides a comprehensive understanding biological systems. With advanced analytical techniques, metabolomics exhibits unprecedented significant value basic drug research, including disease mechanisms, identifying targets, and elucidating mode action drugs. More importantly, greatly accelerates development process by predicting pharmacokinetics, pharmacodynamics, response. In addition, facilitates exploration repurposing drug-drug interactions, as well personalized treatment strategies. Here, we briefly review recent advances technologies update our knowledge applications research development.

Language: Английский

Citations

33
SARS-CoV-2 mitochondrial metabolic and epigenomic reprogramming in COVID-19 DOI Creative Commons
Joseph W. Guarnieri, Jeffrey Haltom, Yentli E. Soto Albrecht

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 204, P. 107170 - 107170

Published: April 12, 2024

To determine the effects of SARS-CoV-2 infection on cellular metabolism, we conducted an exhaustive survey metabolic pathways modulated by and confirmed their importance for propagation cataloging specific pathway inhibitors. This revealed that strongly inhibits mitochondrial oxidative phosphorylation (OXPHOS) resulting in increased reactive oxygen species (mROS) production. The elevated mROS stabilizes HIF-1α which redirects carbon molecules from oxidation through glycolysis pentose phosphate (PPP) to provide substrates viral biogenesis. also induces release DNA (mtDNA) activates innate immunity. restructuring energy metabolism is mediated part Orf8 Orf10 whose expression restructures nuclear (nDNA) mtDNA OXPHOS gene expression. These proteins likely alter epigenome, either directly altering histone modifications or modulating metabolite epigenome modification enzymes, potentially silencing contributing long-COVID.

Language: Английский

Citations

13
Biosynthesis of Nicotinamide Mononucleotide: Synthesis Method, Enzyme, and Biocatalytic System DOI
Feng Cheng, Kexin Li,

Shanshan Wu

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(7), P. 3302 - 3313

Published: Feb. 8, 2024

Nicotinamide mononucleotide (NMN) has garnered substantial interest as a functional food product. Industrial NMN production relies on chemical methods, facing challenges in separation, purification, and regulatory complexities, leading to elevated prices. In contrast, biosynthesis through fermentation or enzyme catalysis offers notable benefits like eco-friendliness, recyclability, efficiency, positioning it primary avenue for future synthesis. Enzymatic synthesis encompasses the nicotinamide-initial route nicotinamide ribose-initial routes. Key among these is riboside kinase (NRK), pivotal latter route. The NRK-mediated emerging prominent trend due its streamlined route, simplicity, precise specificity. essential aspect obtain an engineered NRK that exhibits activity robust stability. This review comprehensively assesses diverse offering valuable insights into efficient, sustainable, economical It spotlights pathway significance. establishment of adenosine triphosphate (ATP) regeneration system plays role enhancing efficiency NRK-catalyzed aims be reference researchers developing green sustainable synthesis, well those optimizing production.

Language: Английский

Citations

10
NAD+ metabolism-based immunoregulation and therapeutic potential DOI Creative Commons
Jiankai Fang,

Wangwang Chen,

Pengbo Hou

et al.

Cell & Bioscience, Journal Year: 2023, Volume and Issue: 13(1)

Published: May 10, 2023

Abstract Nicotinamide adenine dinucleotide (NAD + ) is a critical metabolite that acts as cofactor in energy metabolism, and serves cosubstrate for non-redox NAD -dependent enzymes, including sirtuins, CD38 poly(ADP-ribose) polymerases. metabolism can regulate functionality attributes of innate adaptive immune cells contribute to inflammatory responses. Thus, the manipulation bioavailability reshape courses immunological diseases. Here, we review basics biochemistry its roles response, discuss current challenges future translational potential research development therapeutics diseases, such COVID-19.

Language: Английский

Citations

18
NAD+ Metabolism and Immune Regulation: New Approaches to Inflammatory Bowel Disease Therapies DOI Creative Commons
Chaoyue Chen,

Wei Yan,

Meihui Tao

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(6), P. 1230 - 1230

Published: June 7, 2023

Inflammatory bowel disease (IBD), which includes Crohn’s (CD) and ulcerative colitis (UC), is a multifactorial systemic inflammatory immune response. Nicotinamide adenine dinucleotide (NAD+) co-enzyme involved in cell signaling energy metabolism. Calcium homeostasis, gene transcription, DNA repair, communication involve NAD+ its degradation products. There growing recognition of the intricate relationship between diseases In case IBD, maintenance intestinal homeostasis relies on delicate balance biosynthesis consumption. Consequently, therapeutics designed to target pathway are promising for management IBD. This review discusses metabolic immunoregulatory processes IBD examine molecular biology pathophysiology regulation provide evidence theoretical support clinical use

Language: Английский

Citations

18
Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID DOI Creative Commons
A. Satyanarayan Naidu, Chin‐Kun Wang, Pingfan Rao

et al.

npj Science of Food, Journal Year: 2024, Volume and Issue: 8(1)

Published: March 30, 2024

Language: Английский

Citations

8
Mutation of a highly conserved isoleucine residue in loop 2 of several 𝛽-coronavirus macrodomains indicates that enhanced ADP-ribose binding is detrimental to infection DOI Creative Commons
Catherine M. Kerr, Jessica J. Pfannenstiel, Yousef M. Alhammad

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 4, 2024

All coronaviruses (CoVs) encode for a conserved macrodomain (Mac1) located in nonstructural protein 3 (nsp3). Mac1 is an ADP-ribosylhydrolase that binds and hydrolyzes mono-ADP-ribose from target proteins. Previous work has shown important virus replication pathogenesis. Within Mac1, there are several regions highly across CoVs, including the GIF (glycine-isoleucine-phenylalanine) motif. To determine how biochemical activities of these residues impact CoV replication, isoleucine phenylalanine were mutated to alanine (I-A/F-A) both recombinant proteins murine hepatitis (MHV), Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute 2 (SARS-CoV-2). The F-A mutant had ADP-ribose binding and/or hydrolysis defects led attenuated pathogenesis cell culture mice. In contrast, I-A mutations normal enzyme activity enhanced binding. Despite increased binding, MERS-CoV SARS-CoV-2 mice, indicating this residue acts as gate controls efficient replication. These results highlight function provide unique insight into macrodomains control promote viral

Language: Английский

Citations

6