Use of Nicotinamide Mononucleotide as Non-Natural Cofactor

Catalysts, Год журнала: 2025, Номер 15(1), С. 37 - 37

Опубликована: Янв. 3, 2025

Nicotinamide mononucleotide (NMN) has emerged as a promising non-natural cofactor with significant potential to transform biocatalysis, synthetic biology, and therapeutic applications. By modulating NAD⁺ metabolism, NMN offers unique advantages in enzymatic reactions, metabolic engineering, regenerative medicine. This review provides comprehensive analysis of NMN’s biochemical properties, mechanisms action, diverse Emphasis is placed on its role addressing challenges multi-enzyme cascades, biofuel production, the synthesis high-value chemicals. The paper also highlights critical research gaps, including need for scalable methods, improved integration into systems, toxicity studies use. Emerging technologies such AI-driven enzyme design CRISPR-based genome engineering are discussed transformative tools optimizing NMN-dependent pathways. Furthermore, synergistic biology innovations, cell-free systems dynamic regulatory networks, explored, paving way precise modular biotechnological solutions. Looking forward, versatility positions it pivotal tool advancing sustainable bioprocessing precision Addressing current limitations through interdisciplinary approaches will enable redefine boundaries innovation. serves roadmap leveraging across scientific industrial domains.

Язык: Английский

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Implication of protein post translational modifications in gastric cancer

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Фев. 4, 2025

Gastric cancer (GC) is one of the most common and highly lethal malignant tumors worldwide, its occurrence development are regulated by multiple molecular mechanisms. Post-translational modifications (PTM) forms include ubiquitylation, phosphorylation, acetylation methylation. Emerging research has highlighted lactylation glycosylation. The diverse realm PTM crosstalk linked to many critical signaling events involved in neoplastic transformation, carcinogenesis metastasis. This review provides a comprehensive overview impact on progression GC. Specifically, aberrant have been shown alter proliferation, migration, invasion capabilities GC cells. Moreover, closely associated with resistance chemotherapeutic agents Notably, this also discusses phenomenon crosstalk, highlighting interactions among their roles regulating pathways protein functions. Therefore, in-depth investigation into mechanisms targeted therapeutic strategies hold promise for advancing early diagnosis, treatment, prognostic evaluation GC, offering novel insights future directions.

Язык: Английский

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Epigenomic Echoes—Decoding Genomic and Epigenetic Instability to Distinguish Lung Cancer Types and Predict Relapse

Epigenomes, Год журнала: 2025, Номер 9(1), С. 5 - 5

Опубликована: Фев. 5, 2025

Genomic and epigenomic instability are defining features of cancer, driving tumor progression, heterogeneity, therapeutic resistance. Central to this process epigenetic echoes, persistent dynamic modifications in DNA methylation, histone modifications, non-coding RNA regulation, chromatin remodeling that mirror underlying genomic chaos actively influence cancer cell behavior. This review delves into the complex relationship between these illustrating how they collectively shape genome, affect repair mechanisms, contribute evolution. However, dynamic, context-dependent nature changes presents scientific ethical challenges, particularly concerning privacy clinical applicability. Focusing on lung we examine specific patterns function as biomarkers for distinguishing subtypes monitoring disease progression relapse.

Язык: Английский

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Selisistat, a SIRT1 inhibitor, enhances paclitaxel activity in luminal and triple-negative breast cancer: in silico, in vitro, and in vivo studies

Journal of Enzyme Inhibition and Medicinal Chemistry, Год журнала: 2025, Номер 40(1)

Опубликована: Фев. 12, 2025

Sirtuins (SIRTs) are NAD+-dependent histone deacetylases, which play a key role in cancer progression; however, their prognostic values breast (BC) remain subject of debate and controversy. Accumulative evidence suggests that each sirtuin possesses individual character, implicating its the regulation multifaceted biological functions leading to BC initiation, progression metastasis. Selisistat (EX527) is potent, cell permeable, highly selective SIRT1 inhibitor. In study, tumour-suppressive effects inhibitor EX527 (selisistat) alone combination with paclitaxel (PAX) different lines zebrafish xenograft models were investigated. The type pharmacological drug-drug interaction between PAX was determined using isobolographic method. used individually inhibited proliferation, induced apoptosis caused cycle arrest G1 subG1/G2 phases. Interestingly, these compounds 1:1 dose-ratio augmented all (IC50add 29.52 ± 3.29 − 38.45 5.26). co-treatment generated desirable additive interaction. simultaneous application stronger inhibition tumour growth compared treatments xenografts. silico analysis revealed protein-protein pathway (SIRT1-AKT-S1PR1-GNAI1/GNAO1-Tubulin) connecting molecular targets both ligands. To summarise, more effectively impairs treatments. However, further investigations required clarify specific mechanisms underlying activity EX527:PAX other preclinical models.

Язык: Английский

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Sirtuins and Gut Microbiota: Dynamics in Health and a Journey from Metabolic Dysfunction to Hepatocellular Carcinoma

Cells, Год журнала: 2025, Номер 14(6), С. 466 - 466

Опубликована: Март 20, 2025

Metabolic dysfunction leading to non-alcoholic fatty liver disease (NAFLD) exhibits distinct molecular and immune signatures that are influenced by factors like gut microbiota. The microbiome interacts with the via a bidirectional relationship gut–liver axis. Microbial metabolites, sirtuins, responses pivotal in different metabolic diseases. This extensive review explores complex multifaceted interrelationship between sirtuins microbiota, highlighting their importance health disease, particularly hepatocellular carcinoma (HCC). Sirtuins (SIRTs), classified as group of NAD+-dependent deacetylases, serve crucial modulators wide spectrum cellular functions, including pathways, inflammatory response, process senescence. Their subcellular localization diverse functions link them various conditions, NAFLD cancer. Concurrently, comprising microorganisms, significantly influences host metabolism responses. Recent findings indicate modulate microbiota composition function, while can affect sirtuin activity. is relevant disorders, where dysbiosis contributes progression. highlights recent on roles specific maintaining implications HCC development. Understanding these interactions offers potential therapeutic avenues for managing diseases linked dysregulation pathology.

Язык: Английский

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Sirtuin 5 (SIRT5) Suppresses Tumor Growth by Regulating Mitochondrial Metabolism and Synaptic Remodeling in Gliomas

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(16), С. 9125 - 9125

Опубликована: Авг. 22, 2024

Sirtuin 5 (SIRT5) is increasingly recognized as a key regulator of cellular metabolism, which commonly dysregulated in cancer cells, resulting enhanced proliferation and tumor progression. To investigate the clinicopathologic implications SIRT5 dysregulation glioblastoma, we performed comprehensive analyses transcriptomic data functional verifications using vitro vivo glioblastoma models. We found that higher expression levels were associated with favorable prognosis glioma patients. Knockdown significantly cell growth. Our suggest its potential role regulating mitochondrial metabolism gliomas. Furthermore, also correlated synaptic remodeling pathways. findings indicate tumor-suppressive for extends beyond by it may function through modulating neuroplasticity. Understanding these interactions provides nuanced insights into multifaceted broader therapeutic this development novel treatment strategies.

Язык: Английский

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Design, synthesis and biological evaluation of prostate-specific membrane antigen (PSMA)-targeted SIRT2 inhibitors

Bioorganic Chemistry, Год журнала: 2024, Номер 153, С. 107784 - 107784

Опубликована: Сен. 16, 2024

Язык: Английский

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Sirtuins: Emergent Players in Tissue and Organ Regeneration

International Journal of Translational Medicine, Год журнала: 2024, Номер 4(4), С. 687 - 709

Опубликована: Дек. 2, 2024

Sirtuins are a family of lysine deacetylases that regulate cellular homeostasis and energy sensing. Regeneration is the process restores structural functional at cellular, tissue, organ, appendage levels. Several processes, such as epithelial–mesenchymal transition (EMT), proliferation, migration, differentiation, contribute to restoration after an injury. This review highlights role sirtuins in anatomical structure regeneration, showing how modulate signalling pathways by deacetylating targets transcription factors. Furthermore, understanding this protein could help elucidate molecular mechanisms underlying tissue which may hold significant potential for fields regenerative medicine. The compiles evidence suggesting emerging factors regeneration various organs (e.g., skin, liver, heart) tissues bone, muscle, cornea, spinal cord).

Язык: Английский

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SIRT2 deacetylates and decreases the expression of FOXM1 in colon cancer

Journal of Biochemical and Molecular Toxicology, Год журнала: 2024, Номер 38(11)

Опубликована: Окт. 18, 2024

Abstract New FOXM1‐specific inhibitors with the potential to be used for therapeutic purposes are under extensive research. We hypothesized that deacetylation of FOXM1 would decrease protein expression, thus providing novel management colon cancers. Immunostaining was determine and SIRT2 expressions in human cancer tissue microarrays ( n = 90) from Stage I IV. SIRT2‐FOXM1 interaction evaluated cells using immunoprecipitation. Deacetylation via determined vitro assays. could hyper‐acetylated when p300 pCAF histone acetyltransferases were administered alongside deacetylase inhibitors. detected physically interacted, deacetylated vitro. overexpression led a significant while knockdown increased expression HCT116 carcinoma cells. In analysis 90 colorectal samples, high observed about 49% cancer, intermediate 29%, low or no staining 22%. Strong found negatively associated our clinical cohort. This study reveals molecular association between cell lines suggests targeting activity small molecule modulators may promising approach cancer.

Язык: Английский

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Role of Nicotinamide in the Pathogenesis of Actinic Keratosis: Implications for NAD+/SIRT1 Pathway

Biomolecules, Год журнала: 2024, Номер 14(12), С. 1512 - 1512

Опубликована: Ноя. 27, 2024

Actinic keratosis (AK) is a precursor to invasive squamous cell carcinoma, making early diagnosis and treatment essential prevent progression. Among available therapeutic options, nicotinamide (NAM) has shown potential in reducing AK NAM of adenine dinucleotide (NAD+), which activates sirtuin (SIRT)1, protein with anti-cancer properties. Although the role SIRT1 still debated, no data currently exist on systemic modulation this AK. Therefore, study aims evaluate whether NAM, by increasing serum NAD+ levels, may promote activation peripheral blood mononuclear cells (PBMCs) patients. Thirty patients were enrolled treated for 24 months. Hematological, biochemical, skin condition assessments conducted, alongside measurement levels. A decrease basophils, monocytes, total cholesterol, glucose levels was observed group, along reduction lesions. Notably, significantly enhanced nuclear activity PBMCs. In conclusion, administration reduced progression NAD+/SIRT1-dependent manner, supporting its as chemopreventive agent management.

Язык: Английский

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