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Multiple myeloma, a quintessential malignant disease of aging: a geroscience perspective on pathogenesis and treatment.

Multiple myeloma (MM) is an incurable plasma cell malignancy, which is predominantly a disease of older adults (the median age at diagnosis is 70 years). The slow progression from asymptomatic stages and the late-onset of MM suggest fundamental differences compared to many other hematopoietic system-related malignancies. The concept discussed in this review is that age-related changes at the level of terminally differentiated plasma cells act as the main risk factors for the development of MM. Epigenetic and genetic changes that characterize both MM development and normal aging are highlighted

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… Nicotinamide mononucleotide (NMN) supplementation promotes neurovascular rejuvenation in aged mice: transcriptional footprint of SIRT1 activation, mitochondrial protection, anti-inflammatory, and anti-apoptotic effects. … Kiss T Giles CB Tarantini S Yabluchanskiy A Balasubramanian P Gautam T Nicotinamide mononucleotide (NMN) supplementation promotes anti-aging miRNA expression profile in the aorta of aged mice, predicting epigenetic rejuvenation and anti-atherogenic effects Geroscience 2019 41 419 439 31463647 10.1007 …

Окисляющий/нетрозирующий стресс, апоптоз и сигнализация " Redox " : основные игроки в нейродегенеративных заболеваниях.

Нейродегенеративные заболевания представляют собой серьезную проблему для здоровья, которая оказывает глубокое воздействие на качество и продолжительность жизни миллионов людей. Эти заболевания характеризуются патологическими изменениями в различных областях мозга, конкретными генетическими мутациями, связанными с болезнью, залежами аномальных белков и дегенерацией неврологических клеток. Поскольку нейродегенеративные расстройства различаются по своим эпидемиологическим характеристикам и степени уязвимости нейронов, лечение этих заболеваний обычно направлено на замедление развития заболеваний.

Anticancer Activities of Novel Nicotinamide Phosphoribosyltransferase Inhibitors in Hematological Malignancies.

Targeting cancer cells that are highly dependent on the nicotinamide adenine dinucleotide (NAD+) metabolite is a promising therapeutic strategy. Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme catalyzing NAD+ production. Despite the high efficacy of several developed NAMPT inhibitors (i.e., FK866 (APO866)) in preclinical studies, their clinical activity was proven to be limited. Here, we report the synthesis of new NAMPT Inhibitors, JJ08, FEI191 and FEI199, which exhibit a broad anticancer activity in vitro. Results show that these compounds are potent NAMPT inhibito

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… Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme that catalyzes the phosphoribosylation of NAM to produce nicotinamide mononucleotide (NMN) [ 9 , 10 ]. Then, the latter is converted to NAD + , a process catalyzed by NMN adenyltransferase. …

Распознавание ксантиновой реберосколочной структуры и металлическое ионопосредованное распознавание лиганда.

Рибосколки сохраняют функциональные области в MRNA, которые в основном существуют в бактериях. Они регулируют генное выражение в ответ на различные концентрации метаболитов или металлических ионов. Недавно был выявлен мотив РНК NMT1 для селективной привязки ккантиновой и мочевой кислот, соответственно, к метаболическому пути деградации пурины. Вот, мы сообщаем о кристаллической структуре этой РНК, связанной с ксантиной. В целом рибосуха имеет стержень, постоянно сложенный в сложенном виде three стебли и two внутренние перекрестки. Связующий карман определяется высокоохранной соединенной послед

Bone Marrow Adipocytes, Adipocytokines, and Breast Cancer Cells: Novel Implications in Bone Metastasis of Breast Cancer.

Accumulating discoveries highlight the importance of interaction between marrow stromal cells and cancer cells for bone metastasis. Bone is the most common metastatic site of breast cancer and bone marrow adipocytes (BMAs) are the most abundant component of the bone marrow microenvironment. BMAs are unique in their origin and location, and recently they are found to serve as an endocrine organ that secretes adipokines, cytokines, chemokines, and growth factors. It is reasonable to speculate that BMAs contribute to the modification of bone metastatic microenvironment and affecting metastatic br

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… Visfatin also accelerates VSMC proliferation through nicotinamide mononucleotide-mediated activation of ERK 1/2 and p38 signaling pathways ( 155 ). In addition, visfatin reduces apoptosis in endothelial cells and induces maturation in human VSMC ( 153 ). … Perivascular adipose tissue-derived visfatin is a vascular smooth muscle cell growth factor: role of nicotinamide mononucleotide . Cardiovasc Res . ( 2009 ) 81 : 370 – 80 . 10.1093/cvr/cvn288 18952695 156. Chen S-S Tang C-H Chie M-J Tsai C-H Fong Y-C Lu Y-C . …

Resveratrol and Its Role in the Management of B-Cell Malignancies-A Recent Update.

The growing incidence of B cell malignancies globally has prompted research on the pharmacological properties of phytoconstituents in cancer management. Resveratrol, a polyphenolic stilbenoid widely found in nature, has been explored for its anti-inflammatory and antioxidant properties, and promising results from different pre-clinical studies have indicated its potential for management of B cell malignancies. However, these claims must be substantiated by a greater number of clinical trials in diverse populations, in order to establish its safety and efficacy profile. In addition to this, the

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… Legend: ROS: Reactive oxygen species, BBB: Blood brain barrier, NMN: Nicotinamide mononucleotide. … . | 5 mg resveratrol, one capsule a day | Antioxidant potential, reduction of inflammation, triggering of cellular apoptosis Resveratrol+ Nicotinamide mononucleotide (NMN) | Lifespan supplements- Nutraceutical capsules | 300 mg resveratrol, once a day | Improved vascular functioning, enhancement of DNA …

Bortezomib-induced peripheral neuropathy: from molecular mechanisms to clinical management.

Bortezomib (BTZ) is a first-generation proteasome inhibitor that has shown significant efficacy in the treatment of multiple myeloma (MM), providing significant therapeutic benefits without severely compromising overall patient health. However, one of the most common and debilitating side effects associated with BTZ therapy is bortezomib-induced peripheral neuropathy (BIPN). This condition is the leading complication observed in patients undergoing BTZ treatment and has a profound impact on treatment regimens, often necessitating dose reductions or alterations in the dosing schedule. Despite t

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… mononucleotide adenylyltransferase 2; PK2, recombinant prokinetic peptide 2; P0, Peripheral Myelin P0 Protein; P2XRs, purinergic 2X receptors; ROS, reactive oxygen species; S1P, sphingosine-1-phosphate; S1PR1, recombinant sphingosine-1-phosphate receptor 1; SARM1, sterility 1 containing α and Toll/interleukin … In addition, BTZ triggers the axonal degeneration program: decreasing axonal Nicotinamide mononucleotide adenylyltransferase 2 levels, activating Sterility 1 containing α and Toll/interleukin-1 receptor motifs (SARM1), and depleting nicotinamide adenine dinucleotide, a process regulated by caspase-mediated …

Crosstalk between Circadian Rhythm Dysregulation and Tumorigenesis, Tumor Metabolism and Tumor Immune Response.

Circadian rhythm is a self-regulating 24-hour system that synchronizes with the day and night cycle in organisms. The regulation of this system is controlled by clock genes, which function to harmoniously express molecular levels that facilitate the orderly coordination of various cellular processes, such as sleep, metabolism, endocrine function, cell proliferation and immunity. The root cause of tumorigenesis is that the body loses its normal regulation of cell growth at the genetic level. Long-term disruptions in circadian rhythms caused by factors such as shift work, jet lag, and unstable s

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… NAMPT facilitates transfer of a phosphoribosyl residue from 5-phosphoribosyl-1- pyrophosphate (PRPP) to nicotinamide, resulting in the production of nicotinamide mononucleotide (NMN) that is further converted to NAD + by nicotinamide mononucleotide adenylyltransferases (NMNATs). …

Metabolic reprogramming in T cell senescence: a novel strategy for cancer immunotherapy.

The complex interplay between cancer progression and immune senescence is critically influenced by metabolic reprogramming in T cells. As T cells age, especially within the tumor microenvironment, they undergo significant metabolic shifts that may hinder their proliferation and functionality. This manuscript reviews how metabolic alterations contribute to T cell senescence in cancer and discusses potential therapeutic strategies aimed at reversing these metabolic changes. We explore interventions such as mitochondrial enhancement, glycolytic inhibition, and lipid metabolism adjustments that co

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… NAD+ precursors, such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), have garnered significant attention due to their ability to restore NAD+ levels and improve mitochondrial function. …

Nucleotide Metabolism in Health and Disease.

Nucleotide metabolism is a fundamental biochemical process, providing the building blocks for DNA and RNA synthesis while driving critical cellular functions like energy transfer, signal transduction, and coenzyme synthesis. The precise regulation of nucleotide de novo synthesis, salvage, and degradation pathways is imperative for maintaining genomic stability and tissue homeostasis. Aberrations in these networks are increasingly recognized as primary drivers in various pathologies; notably, cancer cells exploit metabolic-functional reprogramming to enable rapid proliferation and therapeutic r

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… Rather, they are more accurately characterized as nicotinamide mononucleotide (NMN) and flavin mononucleotide derivatives, respectively. …

Bortezomib-induced aerobic glycolysis contributes to chemotherapy-induced painful peripheral neuropathy.

Chemotherapy-induced painful peripheral neuropathy (CIPN) is the most common toxicity associated with widely used chemotherapeutics. CIPN is the major cause of dose reduction or discontinuation of otherwise life-saving treatment. Unfortunately, CIPN can persist in cancer survivors, which adversely affects their quality of life. Moreover, available treatments are vastly inadequate, warranting a better understanding of the biochemical and metabolic mechanisms that occur in response to chemotherapeutics which would be critical for the development of novel therapies for CIPN. Using extracellular f

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… Nicotinamide mononucleotide adenylyl transferase-mediated axonal protection requires enzymatic activity but not increased levels of neuronal nicotinamide adenine dinucleotide. J Neurosci 2009; 29: 5525–5535. 63. Windebank AJ, Grisold W. Chemotherapy-induced neuropathy. …

Targeting immunosenescence for improved tumor immunotherapy.

Tumor immunotherapy has significantly transformed the field of oncology over the past decade. An optimal tumor immunotherapy would ideally elicit robust innate and adaptive immune responses within tumor immune microenvironment (TIME). Unfortunately, immune system experiences functional decline with chronological age, a process termed "immunosenescence," which contributes to impaired immune responses against pathogens, suboptimal vaccination outcomes, and heightened vulnerability to various diseases, including cancer. In this context, we will elucidate hallmarks and molecular mechanisms underly

Витамины в профилактике и терапии нейродегенеративных заболеваний.

Нейродегенеративные заболевания, такие, как болезнь Альцгеймера (AD), болезнь Паркинсона (PD), амиотропический боковой склероз (ALS) и множественный склероз (MS), которые являются следствием постепенной потери нейронной функции и структуры, вызывают значительное когнитивное расстройство. Заболеваемость этими заболеваниями среди населения мира постоянно растет в результате старения населения. Хотя генетические и экологические факторы чаще всего упоминаются в качестве патогенетических факторов этих заболеваний, все больше фактов свидетельствует о важной роли надлежащего питания в профилактике и

АнтиCD38 моноколональные антитела в множестве миеломы и за ее пределами: иммунотерапевтические механизмы, зрелость улик и клиническое позиционирование.

АнтиCD38 моноколональные антитела стали центральной иммунотерапевтической платформой во множестве миэломы, где они изменили курс лечения от рецидива или рефракторного заболевания, передней терапии, интенсификации технического обслуживания и минимального управления, ориентированного на остаточные заболевания. Их успех в многочисленных миеломах также стимулировал более широкое развитие в области иммуноглобулинового светового амилоида, отдельных гематологовых магнелез и юморальных иммунных расстройств. CD38 функционирует как как поверхностная мишень, так и как эктоэнзим, связанный с метаболизмом

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… Although CD38 was initially characterized as an ADP-ribosyl cyclase, it is now recognized as a major regulator of nicotinamide adenine dinucleotide (NAD+) and nicotinamide mononucleotide metabolism ( 14 , 17 ). …

Epigenetic Mechanisms Involved in the Cardiovascular Toxicity of Anticancer Drugs.

The cardiovascular toxicity of anticancer drugs promotes the development of cardiovascular diseases. Therefore, cardiovascular toxicity is an important safety issue that must be considered when developing medications and therapeutic applications to treat cancer. Among anticancer drugs, members of the anthracycline family, such as doxorubicin, daunorubicin and mitoxantrone, are known to cause cardiotoxicity and even heart failure. Using human-induced pluripotent stem cell-derived cardiomyocytes in combination with "Omic" technologies, we identified several cardiotoxicity mechanisms and signal t

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… Changes in DNA methylation levels are particularly evident in the kelch-like family member 29 (Klhl29) and the Nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2) gene, where they are associated with changes in mRNA gene expression. …

The sirtuin family in health and disease.

Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, and are involved in numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions. Notably, this protein family plays a variety of important roles in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a

Circadian clock and cancer.

Circadian rhythms play a critical role in regulating physiological and behavioral processes, such as the sleep-wake cycle, hormone secretion, and metabolism. These rhythms are controlled by endogenous biological clocks, which are synchronized with environmental cues, primarily the light-dark cycle. Notably, disruption or reprogramming of circadian rhythms is closely associated with cancer initiation, progression, and treatment response. At the molecular level, the dysregulation of core clock genes can disturb normal cellular rhythms, leading to aberrant cell proliferation, impaired DNA repair,

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… Nicotinamide mononucleotide; NMNAT. Nicotinamide mononucleotide adenylyltransferase; NPAS2 Neuronal PAS domain protein 2; OXPHOS. Oxidative phosphorylation; PARP1. Poly (ADP-ribose) polymerase 1; PEP. Phosphoenolpyruvate; PER2. Period 2; PFK. Phosphofructokinase; PKM2. Pyruvate kinase M2; PPARα. …

Role of mitochondria in physiological activities, diseases, and therapy.

Mitochondria are generally considered essential for life in eukaryotic organisms because they produce most of the energy or adenosine triphosphate (ATP) needed by the cell. Beyond energy production, it is now widely accepted that mitochondria also play a pivotal role in maintaining cellular homeostasis and signaling. The two core processes of mitochondrial dynamics, fission and fusion, serve as crucial foundations for maintaining mitochondrial morphology, distribution, and quantity, thereby ensuring cellular homeostasis. Mitochondrial autophagy (mitophagy) ensures the selective degradation of

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… Recent studies show that nicotinamide mononucleotide (NMN) administration can restore NAD+ levels, prevent ovarian atrophy, and enhance oocyte quality and quantity. It also improves serum hormone secretion, antioxidant factors, and mitochondrial function while reducing inflammation. …

The cGAS-STING pathway in senescence and aging-related diseases: mechanisms and therapeutic opportunities.

The cGAS-STING pathway acts as a critical molecular hub connecting genomic instability with cellular senescence. Functioning as a key regulator of the innate immune system, this pathway detects aberrant cytoplasmic DNA to activate downstream inflammatory responses, thereby playing a pivotal role in aging-related diseases. This review systematically explores the core mechanisms by which the cGAS-STING pathway regulates cellular senescence, emphasizing its role in triggering senescence through the recognition of DNA damage signals (e.g., oxidative stress, telomere dysfunction) and promoting para

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… mononucleotide (NMN) | Effectively counteracts inflammation | [ 74 , 305 ] Selective clearance of senescent cells to reduce DNA damage burden | ABT263, Dasatinib + Quercetin | Reduces oxidative stress, DNA damage, and SASP; restores impaired metabolism in obese models | [ 306 , 307 ] Block downstream … Additionally, nicotinamide mononucleotide (NMN), a key NAD + precursor, counteracts inflammation by preventing VDAC1-mediated mtDNA release under conditions of NAD + depletion [ 74 , 305 ]. …

Second primary cancers following hematologic malignancies: Epidemiology, pathobiology and clinical management.

Second primary cancers (SPCs) pose an increasingly significant clinical challenge for survivors of hematologic malignancies, attributed to improved therapeutic outcomes and prolonged survival. The development of SPCs is influenced by a complex interplay of treatment-related factors, genetic susceptibility, immune dysregulation, and microenvironmental remodeling. This narrative review summarizes the epidemiological patterns of SPCs in survivors of hematologic malignancies and discusses the underlying biological mechanisms, including therapy-induced genomic instability, clonal hematopoiesis, inf

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… For instance, preclinical models have shown that replenishing intracellular pools of nicotinamide adenine dinucleotide (NAD + ) through nicotinamide mononucleotide (NMN) facilitates poly (ADP-ribose) polymerase (PARP)-mediated DNA repair following fractionated radiotherapy. 115–117 Similarly, senolytic …