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Design and Rationale of Prolonged Nightly Fasting for Multiple Myeloma Prevention (PROFAST): Protocol for a Randomized Controlled Pilot Trial.

BACKGROUND: Obesity is an established, modifiable risk factor of multiple myeloma (MM); yet, no lifestyle interventions are routinely recommended for patients with overweight or obesity with MM precursor conditions. Prolonged nightly fasting is a simple, practical dietary regimen supported by research, suggesting that the synchronization of feeding-fasting timing with sleep-wake cycles favorably affects metabolic pathways implicated in MM. We describe the design and rationale of a randomized controlled pilot trial evaluating the efficacy of a regular, prolonged nighttime fasting schedule among

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… Adipocyte-lipid content is analyzed using histology, flow cytometry, and lipidomics on adipocyte-enriched fractions. …

Множественный склероз: то, что мы узнали и можем узнать из электронной микроскопии.

Множественный склероз (MS) — воспалительное нейродегенеративное заболевание, характеризующееся возникновением демиелинированных повреждений в центральной нервной системе. Повреждения MS могут подвергаться воспоминанию, временно смягчая симптомы, но по мере развития болезни воспроизводство становится менее эффективным. Помимо повреждений, нормальные появляющиеся ткани мозга имеют тонкие изменения, потенциально указывающие на более широкую диффузную патологию и/или повышенную подверженность воздействию повреждений. Патология MS варьируется между повреждениями серых и белых веществ и их нормальны

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… technique is a powerful tool to study ultrastructural features and complements conventional techniques that are used to study cellular and molecular processes, such as cell culture and animal models, but also for example immunohistochemistry, single nucleus RNA sequencing and spatial transcriptomics, lipidomics …

Glucosylceramide Synthase Inhibitors Induce Ceramide Accumulation and Sensitize H3K27 Mutant Diffuse Midline Glioma to Irradiation.

H3K27M mutant (mut) diffuse midline glioma (DMG) is a lethal cancer with no effective cure. The glycosphingolipids (GSL) metabolism is altered in these tumors and could be exploited to develop new therapies. We tested the effect of the glucosylceramide synthase inhibitors (GSI) miglustat and eliglustat on cell proliferation, alone or in combination with temozolomide or ionizing radiation. Miglustat was included in the therapy protocol of two pediatric patients. The effect of H3.3K27 trimethylation on GSL composition was analyzed in ependymoma. GSI reduced the expression of the ganglioside GD2

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… Sphingolipids Mass Spectrometry for Lipidomics Wiley-VCH GmbH Weinheim, Germany 2023 425 480 80. McLeod C. Gout A.M. Zhou X. Thrasher A. Rahbarinia D. Brady S.W. Macias M. Birch K. Finkelstein D. Sunny J. St. …

Application of NMR-based metabolomics and machine learning for non-invasive disease screening in dogs.

BackgroundBlood-based metabolomics is increasingly recognised as a powerful tool for disease detection in human medicine. However, its application in veterinary science remains limited.ObjectiveTo evaluate the ability of an NMR-based metabolomics platform combined with machine learning to screen dogs for cancer, cardiovascular disease (CVD), and overall health status.AnimalsClient-owned dogs were recruited from two sites. Of 156 animals enrolled, 139 remained after exclusions and were used for training and cross-validation of classification models.MethodsBlood samples were obtained from clinic

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… Lipidomics techniques have advanced our understanding of cancer-specific lipid profiles, revealing potential biomarkers and therapeutic targets ( 69 ). …

Многофункциональная роль аполипопротеина Е в нейродегенеративных заболеваниях.

Генетическое разнообразие в гене аполипопротеина Е (АпоЭ) было определено в качестве основного фактора риска уязвимости в плане генетического риска для спорадического заболевания Альцгеймера (САД). В частности, аллея АпоЕ4 является важным фактором риска для SAD, в то время как аллея АпоЕ2 обеспечивает защиту по сравнению с более распространенными аллеями АпоЕ3. В настоящем обзоре рассматривается роль АпоЭ в АД и других нейродегенеративных расстройствах. ApoE — белок переноса холестерина — влияет на несколько путей нейродегенерации, особенно в AD. Помимо своей установленной роли в метаболизме и

An updated overview of the search for biomarkers of osteoporosis based on human proteomics.

Osteoporosis is a chronic metabolic disease that increases bone fragility and, leads to severe osteoporotic fractures. In recent years, the use of high-throughput omics to explore physiological and pathological biomarkers related to bone metabolism has gained popularity. In this review, we first briefly review the technical approaches of proteomics. Additionally, we summarize the relevant literature in the last decade to provide a comprehensive overview of advances in human proteomics related to osteoporosis. We describe the specific roles of various proteins related to human bone metabolism,

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… MALDI-MSI-LC-MS/MS workflow for single-section single step combined proteomics and quantitative lipidomics. Anal Chem. 2024;96(10):4266–4274. doi: 10.1021/acs.analchem.3c05850. 18. Xu J., Cai X., Miao Z., Yan Y., Chen D., Yang Z.X., et al. …

Extracellular Vesicles After Allogeneic Hematopoietic Cell Transplantation: Emerging Role in Post-Transplant Complications.

Extracellular vesicles (EVs) play an important role in the cellular crosstalk by transferring bioactive molecules through biological barriers from a cell to another, thus influencing recipient cell functions and phenotype. Therefore, EVs are increasingly being explored as biomarkers of disease progression or response to therapy and as potential therapeutic agents in different contexts including in hematological malignancies. Recently, an EV role has emerged in allogeneic hematopoietic cell transplantation (allo-HCT) as well. Allogeneic hematopoietic cell transplantation often represents the on

Navigating the Landscape of Exosomal microRNAs: Charting Their Pivotal Role as Biomarkers in Hematological Malignancies.

Under physiological and pathological conditions, all cells release extracellular vesicles named exosomes, which act as transporters of lipidic, protein, and genetic material from parent to recipient cells. Neoplastic cells can secrete higher number of exosomes to exert pro-tumoral effects such as microenvironmental changes, disease progression, immunosuppression and drug-resistance. This holds true for both organ-specific cancers and hematologic malignancies. One of the most important components of exosomal cargo are microRNAs which can mediate all the abovementioned effects. More specifically

Exposome and unhealthy aging: environmental drivers from air pollution to occupational exposures.

The aging population worldwide is facing a significant increase in age-related non-communicable diseases, including cardiovascular and brain pathologies. This comprehensive review paper delves into the impact of the exposome, which encompasses the totality of environmental exposures, on unhealthy aging. It explores how environmental factors contribute to the acceleration of aging processes, increase biological age, and facilitate the development and progression of a wide range of age-associated diseases. The impact of environmental factors on cognitive health and the development of chronic age

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Myeloid-Derived Suppressor Cells in Sepsis: Pathophysiology, Duality, and Therapeutic Frontiers.

Sepsis-induced immunosuppression, one of the factors contributing to mortality, is closely mediated by myeloid-derived suppressor cells (MDSCs). This review first outlines MDSC biology, describing their origin from pathological emergency myelopoiesis and classification into polymorphonuclear and monocytic subsets. We then discuss their dual role: an early, protective modulation of cytokine storm that later evolves into harmful immunosuppression associated with secondary infections and death. The underlying mechanisms involve L-arginine depletion ( via arginase 1/inducible nitric oxide synthase

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… This will require applying multiomics (metabolomics, lipidomics) and advanced technologies like in vivo metabolic flux imaging to track MDSC metabolic reprogramming across different sepsis stages. …

Cell-Selective Altered Cargo Properties of Extracellular Vesicles Following In Vitro Exposures to Intermittent Hypoxia.

Intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), is associated with cardiovascular and metabolic dysfunction. However, the mechanisms underlying these morbidities remain poorly delineated. Extracellular vesicles (EVs) mediate intercellular communications, play pivotal roles in a multitude of physiological and pathological processes, and could mediate IH-induced cellular effects. Here, the effects of IH on human primary cells and the release of EVs were examined. Microvascular endothelial cells (HMVEC-d), THP1 monocytes, THP1 macrophages M0, THP1 macrophages M1, THP1 macr

The Power of Extracellular Vesicles in Myeloproliferative Neoplasms: "Crafting" a Microenvironment That Matters.

Myeloproliferative Neoplasms (MPN) are acquired clonal disorders of the hematopoietic stem cells and include Essential Thrombocythemia, Polycythemia Vera and Myelofibrosis. MPN are characterized by mutations in three driver genes (JAK2, CALR and MPL) and by a state of chronic inflammation. Notably, MPN patients experience increased risk of thrombosis, disease progression, second neoplasia and evolution to acute leukemia. Extracellular vesicles (EVs) are a heterogeneous population of microparticles with a role in cell-cell communication. The EV-mediated cross-talk occurs via the trafficking of

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… Mass-spectrometry-based molecular characterization of extracellular vesicles: Lipidomics and proteomics. J. Proteome Res. 2015;14:2367–2384. doi: 10.1021/pr501279t. 66. Szczepanski M.J., Szajnik M., Welsh A., Whiteside T.L., Boyiadzis M. …

The future of NMR metabolomics in cancer therapy: towards personalizing treatment and developing targeted drugs?

There has been a recent shift in how cancers are defined, where tumors are no longer simply classified by their tissue origin, but also by their molecular characteristics. Furthermore, personalized medicine has become a popular term and it could start to play an important role in future medical care. However, today, a "one size fits all" approach is still the most common form of cancer treatment. In this mini-review paper, we report on the role of nuclear magnetic resonance (NMR) metabolomics in drug development and in personalized medicine. NMR spectroscopy has successfully been used to evalu

Enhancing the Safety of Nanoparticles in Medicine: Highlights of Progress and Critical Objectives.

Nanoparticles have transformed drug delivery, imaging, vaccination, and precision therapeutics, but their clinical translation remains constrained by safety profiles that are inseparable from material design, biological identity, host factors, and manufacturing. This review critically evaluates recent progress, persistent limitations, and priority objectives for safer nanomedicine. Unlike reviews organized primarily by material class or isolated toxicology endpoints, we integrate physicochemical determinants, protein corona formation, immune recognition, organ disposition, preclinical models,

Machine Learning for Multi-Omics Characterization of Blood Cancers: A Systematic Review.

Artificial Intelligence and machine learning are increasingly used to interrogate complex biological data. This systematic review evaluates their application to multi-omics for the molecular characterization of hematological malignancies, an area with unmet clinical need. We searched PubMed, Embase, Institute of Electrical and Electronics Engineers Xplore, and Web of Science from January 2015 to December 2024. Two reviewers screened records, extracted data, and used a modified appraisal emphasizing explainability, performance, reproducibility, and ethics. From 2847 records, 89 studies met incl

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… Multi-omics studies, including genomics, transcriptomics, proteomics, metabolomics and lipidomics, are generating ever more data of increasing depth and complexity [ 67 ]. The development of single-cell omics, spatial omics, and time series data is further adding to this complexity [ 68 ]. …

Genomic instability and genetic heterogeneity in aging: insights from clonal hematopoiesis (CHIP), monoclonal gammopathy (MGUS), and monoclonal B-cell lymphocytosis (MBL).

Aging is a multifaceted process characterized by a gradual decline in physiological function and increased susceptibility to a range of chronic diseases. Among the molecular and cellular mechanisms driving aging, genomic instability is a fundamental hallmark, contributing to increased mutation load and genetic heterogeneity within cellular populations. This review explores the role of genomic instability and genetic heterogeneity in aging in the hematopoietic system, with a particular focus on clonal hematopoiesis of indeterminate potential (CHIP), monoclonal gammopathy of undetermined signifi

Стратегии защиты от нейропии в множестве склерозов: обновление статуса и формирующиеся парадигмы.

ВВЕДЕНИЕ: MS представляет собой континуум заболеваний, в котором с момента начала и с течением времени происходит злокачественное воспаление и нейродегенерация. Недавний прогресс в недостатке патобиологии MS создает новые перспективы для новых терапевтических стратегий нейрозащиты. ОБЛАСТЬ ПРИМЕНЕНИЯ: Авторы кратко рассматривают механизмы, лежащие в основе воспаления и нейродегенерации в MS, и обсуждают нынешние и формирующиеся стратегии поощрения нейрозащиты в MS. Данные были получены в значительной степени на основе обширного обзора опубликованной литературы, имеющейся на PubMed (до 5 марта

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… The number of the injected neural stem cells inversely correlated with parenchymal brain volume changes [ 82 ], and longitudinal metabolomics/lipidomics of biological fluids showed time- and dose-dependent responses with increased CSF levels of acyl-carnitines and fatty acids [ 82 ]. …

Targeting of mitochondrial fission through natural flavanones elicits anti-myeloma activity.

BackgroundMitochondrial alterations, often dependent on unbalanced mitochondrial dynamics, feature in the pathobiology of human cancers, including multiple myeloma (MM). Flavanones are natural flavonoids endowed with mitochondrial targeting activities. Herein, we investigated the capability of Hesperetin (Hes) and Naringenin (Nar), two aglycones of Hesperidin and Naringin flavanone glycosides, to selectively target Drp1, a pivotal regulator of mitochondrial dynamics, prompting anti-MM activity.MethodsMolecular docking analyses were performed on the crystallographic structure of Dynamin-1-like

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… Lipidomics analyses will be prospectively carried out to clarify the lipid classes affected by Hes and Nar in MM cells. Both Hes and Nar are abundant in Tacle, a triploid citrus whose name name flavour recall the two parents’ cultivars: the Tarocco orange ( C. sinensis L. …

Shutting off the fuel supply to target metabolic vulnerabilities in multiple myeloma.

Pathways that govern cellular bioenergetics are deregulated in tumor cells and represent a hallmark of cancer. Tumor cells have the capacity to reprogram pathways that control nutrient acquisition, anabolism and catabolism to enhance their growth and survival. Tumorigenesis requires the autonomous reprogramming of key metabolic pathways that obtain, generate and produce metabolites from a nutrient-deprived tumor microenvironment to meet the increased bioenergetic demands of cancer cells. Intra- and extracellular factors also have a profound effect on gene expression to drive metabolic pathway

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… A second lipidomics study revealed upregulation of ceramides and phosphatidylethanolamines (PEs) and downregulation of phosphatidylcholines, sphingomyelin and one species of PE in MM patients ( 97 ). …