Studying Alzheimer’s disease through an integrative serum metabolomic and lipoproteomic approach

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 27, 2025

Alzheimer's disease (AD) is the most frequent neurodegenerative disorder worldwide. The great variability in evolution and incomplete understanding of molecular mechanisms underlying AD make it difficult to predict when a patient will convert from prodromal stage dementia. We hypothesize that metabolic alterations present at level brain could be reflected systemic blood serum patients, these used as prognostic biomarkers. This pilot study proposes investigation via nuclear magnetic resonance (NMR) spectroscopy consecutive series patients including 57 affected by dementia (AD-dem) 45 with mild cognitive impairment (MCI) due (MCI-AD). As control group, we considered 31 subjects whom other disorders were excluded (MCI). A panel 26 metabolites 112 lipoprotein-related parameters was quantified logistic LASSO regression algorithm employed identify optimal combination metabolites-lipoproteins their ratios discriminate groups interest. In training set, our model classified AD-dem MCI an accuracy 81.7%. These results reproduced validation set (accuracy 75.0%). Evolution MCI-AD evaluated over time. Patients who displayed decrease MMSE < 1.5 point per year lower progression rate: obtained division 18 rate (MCI-AD LR) 27 higher HR). calculated using 4 features identified LR HR 73.3%. identification potential novel peripheral biomarkers disease, proposed this study, opens new prospect for innovative minimally invasive method its very early stages. approach able sub-stratify identifying those associated faster clinical progression.

Язык: Английский

---

Multi-pathway blood biomarkers to target and monitor multidimensional prevention of cognitive and functional decline (nested in the IN-TeMPO study framed within the world-wide FINGERS network)

Frontiers in Aging Neuroscience, Год журнала: 2025, Номер 17

Опубликована: Май 7, 2025

As the population ages, identification of preventive strategies able to delay cognitive and functional decline associated with aging represents a major challenge. To date, multidimensional approaches seem be effective in reducing or delaying onset age-related diseases. The multicentric randomized controlled trial IN-TeMPO (ItaliaN study Tailored Multidomain interventions Prevent community-dwelling Older adults, ClinicalTrials.gov ID NCT06248723), framed within World-Wide FINGERS network, aims verify efficacy guided multidomain preventing decline. Within this study, we will explore comprehensive array established exploratory blood biomarkers several pathologic processes, including Alzheimer's disease (AD), neurodegeneration, inflammation, senescence sarcopenia, stratify subject risk assess effect on biomarkers. ApoE4 status plasma p-tau217 NfL (neurodegeneration), GFAP IL-6 (inflammation), GDF-15 (senescence/sarcopenia) evaluated all subjects (n = 1,662) both at baseline end (12 months). Exploratory additional measured same time points subgroup 100 subjects: BDNF, ghrelin, IGF-1, irisin redox as markers sarcopenia/senescence oxidative stress, gamma-H2AX PBMCs marker senescence, amyloid beta aggregates plasma, urine erythrocytes supportive AD. Untargeted metabolomics analysis untargeted volatilomics whole performed molecular alterations that may pathogenesis progression diseases frail older adults aim identifying novel potential clinical use multiple laboratory can contribute early trajectories mechanisms underlying multidisciplinary pathological processes.

Язык: Английский

---

In-Situ Metabolic Profiling of Different Kinds of Rheum palmatum L. by Laser Desorption–Dielectric Barrier Discharge Ionization Mass Spectrometry Imaging

Metabolites, Год журнала: 2024, Номер 14(3), С. 131 - 131

Опубликована: Фев. 21, 2024

With its high resolving power and sensitivity, mass spectrometry is considered the most informative technique for metabolite qualitation quantification in plant sciences. However, spatial location information, which crucial exploration of physiological mechanisms, lost. Mass imaging (MSI) able to visualize distribution a large number metabolites from complex sample surface single experiment. In this paper, flexible low-cost laser desorption-dielectric barrier discharge ionization-MSI (LD-DBDI-MSI) platform was constructed by combining an LD system with in-line DBDI source, high-precision translation stage, ambient spectrometer. It can be operated at resolution 20 μm atmospheric environment requires minimal preparation. This study presents images in-situ metabolic profiling two kinds plants different origins, wild farmed

Язык: Английский

---

Unlocking the Power of Human Ferritin: Enhanced Drug Delivery of Aurothiomalate in A2780 Ovarian Cancer Cells

Angewandte Chemie International Edition, Год журнала: 2024, Номер unknown

Опубликована: Авг. 19, 2024

Aurothiomalate (AuTM) is an FDA-approved antiarthritic gold drug with unique anticancer properties. To enhance its activity, we prepared a bioconjugate human apoferritin (HuHf) by attaching some AuTM moieties to surface protein residues. The reaction of excess yielded single adduct, that was characterized ESI MS and ICP-OES analysis, using three mutant ferritins trypsinization experiments. adduct contains ~3 atoms per ferritin subunit, arranged in small cluster bound Cys90 Cys102. MD simulations provided plausible structural model for the cluster. evaluated pharmacological properties found be significantly more cytotoxic than free against A2780 cancer cells mainly due higher uptake. NMR-metabolomics showed HuHf induced qualitatively similar changes treated cells, indicating effects on cell metabolism are approximately same, agreement independent biochemical In conclusion, have demonstrated here molecularly precise formed between exhibits far superior drug, while retaining key mechanistic features. Evidence can serve as excellent carrier this metallodrug.

Язык: Английский

---

NMR Metabolomics of Primary Ovarian Cancer Cells in Comparison to Established Cisplatin-Resistant and -Sensitive Cell Lines

Cells, Год журнала: 2024, Номер 13(8), С. 661 - 661

Опубликована: Апрель 9, 2024

Cancer cell lines are frequently used in metabolomics, such as vitro tumor models. In particular, A2780 cells commonly a model for ovarian cancer to evaluate the effects of drug treatment. Here, we compare NMR metabolomics profiles and cisplatin-resistant with those derived from 10 patients high-grade serous carcinoma (collected during primary cytoreduction before any chemotherapeutic treatment). Our analysis reveals substantial similarity among all but significant differences between them both cells. Notably, patient-derived closer resistant when considering exo-metabolome, whereas they essentially equidistant A2780-resistant terms endo-metabolome. This behavior results dissimilarities levels several metabolites attributable differential modulation underlying biochemical pathways. The most pronounced glycolytic phenotype, mainly diverge others due alterations few specific already known markers resistance.

Язык: Английский

---

Cell Metabolomics to Guide the Design of Metal-Based Compounds

Inorganics, Год журнала: 2024, Номер 12(6), С. 168 - 168

Опубликована: Июнь 15, 2024

Despite the increasing interest in development of novel metal-based compounds for cancer treatment, these molecules are currently poorly characterized mechanistic terms, due to their multiple macromolecular targets inside cells. In this review, we show how 1H NMR metabolomics provides a powerful tool investigate metabolic perturbations induced by metal-compounds The chemical identity and concentration metabolites detected cell lysates respective growth media can be viewed as global fingerprint that describes response drug treatment. framework, applications NMR-based study cellular effects treatment cells with anticancer comprehensively reviewed.

Язык: Английский

---

Trends, key contributors, and emerging issues in honey and breast cancer: A bibliometric analysis from 2014 to 2024

F1000Research, Год журнала: 2025, Номер 14, С. 17 - 17

Опубликована: Янв. 3, 2025

Background Honey, a natural product with diverse bioactive compounds, has been increasingly explored for its potential anticancer properties. This study aims to comprehensively analyze the scientific literature on relationship between honey and breast cancer. Methods A bibliometric analysis was conducted using ScienceDirect database identify publications from 2014 2024. Data publication trends, author collaboration, keyword were extracted gain insight into research landscape. Keyword identified nine distinct clusters, indicating directions regarding role of in cancer treatment. Results Key journals such as Journal Ethnopharmacology Food Chemistry have at forefront disseminating findings this domain, demonstrating strong interdisciplinary approach that bridges traditional medicine modern inquiry. The increasing interest properties honey, evidenced by growing number studies, underlines promising agent prevention Recent advances synthesis theranostic paradigms cerium oxide nanoparticles (CeONPs) highlighted, well selenium nanoconstructs. toxicity quality control Perillae Fructus also highlighted. Conclusions provides comprehensive overview current state knowledge uncovers emerging issues require further investigation.

Язык: Английский

---

Novel NMR-Based Approach to Reveal the ‘Metabolic Fingerprint’ of Cytotoxic Gold Drugs in Cancer Cells

Journal of Proteome Research, Год журнала: 2025, Номер 24(2), С. 813 - 823

Опубликована: Янв. 6, 2025

A combination of pathway enrichment and metabolite clustering analysis is used to interpret untargeted 1H NMR metabolomics data, enabling a biochemically informative comparison the effects induced by panel known cytotoxic gold(I) gold(III) compounds in A2780 ovarian cancer cells. The identification most dysregulated pathways for major classes highlights specific chemical features that lead common biological effects. proposed approach may have broader applicability screening metal-based drug candidate libraries, which always complicated their multitarget nature, support comprehensive interpretation metabolic actions.

Язык: Английский

---

Trends, key contributors, and emerging issues in honey and breast cancer: A bibliometric analysis from 2014 to 2024

F1000Research, Год журнала: 2025, Номер 14, С. 17 - 17

Опубликована: Янв. 20, 2025

Background Honey, a natural product with diverse bioactive compounds, has been increasingly explored for its potential anticancer properties. This study aims to comprehensively analyze the scientific literature on relationship between honey and breast cancer. Methods A bibliometric analysis was conducted using ScienceDirect database identify publications from 2014 2024. Data publication trends, author collaboration, keyword were extracted gain insight into research landscape. Keyword identified nine distinct clusters, indicating directions regarding role of in cancer treatment. Results Key journals such as Journal Ethnopharmacology Food Chemistry have at forefront disseminating findings this domain, demonstrating strong interdisciplinary approach that bridges traditional medicine modern inquiry. The increasing interest properties honey, evidenced by growing number studies, underlines promising agent prevention Recent advances synthesis theranostic paradigms cerium oxide nanoparticles (CeONPs) highlighted, well selenium nanoconstructs. toxicity quality control Perillae Fructus also highlighted. Conclusions provides comprehensive overview current state knowledge uncovers emerging issues require further investigation.

Язык: Английский

---

Metabolomic and lipoproteomic differences and similarities between COVID-19 and other types of pneumonia

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 3, 2025

COVID-19 infection has revealed significant effects on the human blood metabolome and lipoproteome, which have been coherently observed in different cohorts worldwide across various waves of SARS-CoV-2 pandemic. As one main clinical manifestations is a severe acute respiratory illness, it pertinent to explore whether this metabolic/lipoproteomic disturbance associated with symptoms. To purpose we are here reporting comparative1H NMR analyses plasma 252 patients non-COVID-19 interstitial (24 individuals) or lobar (21 pneumonia, all matched by age, gender disease severity. The analysis based 24 metabolites 114 lipoprotein parameters. Several common traits among three groups, albeit some peculiar features characteristic each group. differences were between cases others.

Язык: Английский

---