MTA-SZTE Research Group on Artificial Intelligence

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    Cancer therapy-related cardiotoxicity is associated with distinct alterations of the myocardial lipidome

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    Anthracyclines are key components of various chemotherapy regimens, but their clinical utility is limited by severe cardiotoxic side effects. Previous studies have suggested that anthracycline-induced cardiotoxicity (AIC) may be driven by alterations in myocardial lipid metabolism. This study aimed to systematically explore the cardiac lipidomic landscape of AIC with regard to potential pathomechanisms and novel therapeutic targets.Mass spectrometry-based untargeted lipidomics were performed on myocardial biopsies from 13 patients with AIC (age 53 ± 31 years, 54% female, left ventricular ejection fraction 19 ± 4%) and 15 age- and sex-matched controls. Lipidomic profiles were also compared with 15 patients with other heart failure aetiologies (matched for sex and age). A total of 627 individual lipid species from 22 different lipid classes were analysed. AIC was associated with a lower proportion of polyunsaturated fatty acids towards more monounsaturated and saturated sidechains as well as significant alterations in the proportion of odd-chain fatty acids. Pathway analyses indicated a higher precursor conversion into lysolipids in AIC. This accumulation of lysolipid species was not observed in other heart failure aetiologies and may represent a specific finding in AIC.Anthracycline-induced cardiotoxicity leads to distinct alterations of the myocardial lipidome. Increased levels of myocardial lysolipids were identified as a novel lipidomic trait in AIC, which appears to be distinct from other causes of heart failure. Further research studying pharmacological interventions in lysolipid metabolism for prevention and therapy of AIC is warranted

    Real-World Data Confirm That the Integration of Deuterium Depletion into Conventional Cancer Therapy Multiplies the Survival Probability of Patients

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    Background: Over thirty years of basic research has demonstrated that the deuterium-to-hydrogen ratio plays a pivotal role in regulating metabolism and cell growth via a sub-molecular regulatory system that orchestrates the intricate complexity of life in eukaryotic organisms. Deuterium depletion, achieved through deuterium-depleted water (DDW), has shown anticancer effects in vitro, in vivo, and in Phase 2 prospective and retrospective clinical studies. Methods: In this population-based observational study, 2649 cancer patients undergoing conventional therapy and consuming DDW were included between October 1992 and October 2024. With various cancer types and stages and conventional therapies received, they are representing a broad spectrum of the Hungarian cancer population. Survival was selected as the primary endpoint, and the median survival time (MST) of these patients and various subgroups was calculated and compared to the overall Hungarian cancer population’s MST of 2.4 years. Results: For the entire study population, MST from diagnosis was 12.4 years (95% CI: 9.8–14.9), and from the initiation of DDW treatment, 7.6 years (95% CI: 5.9–9.3). Conclusions: Utilizing DDW enables targeted intervention in the sub-molecular regulatory system, paving the way for innovative therapeutic applications and a more profound understanding of cellular processes. Integrating deuterium depletion into conventional cancer therapies has the potential to significantly enhance survival rates and reduce cancer-related mortality by 75–80%

    Continuous high-yield fast neutron generation with few-cycle laser pulses at 10 Hz for applications

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    We present a laser-based neutron source that produces 1.8 × 10 5 neutrons/s with a conversion rate of 7.8 × 10 5 neutrons/J . Laser pulses of 12 fs and 23 mJ were focused onto a 430 -nm -thick heavy water liquid sheet at a 10 Hz repetition rate. The resulting peak intensity of 4 × 10 18 W/cm 2 accelerated deuterium ions from the target rear side to a kinetic energy of 1 MeV. This deuteron beam induced H 2 ( d , n ) 3 He fusion reactions in a deuterated polyethylene target, producing fast neutrons. The neutron yield was measured using two independent detection systems: the LILITH time-of-flight spectrometer, consisting of eight plastic scintillators covering nearly 180 ∘ , and a calibrated bubble detector spectrometer. The neutron yield per laser shot is 35 times higher than that recently achieved by lasers with comparable pulse energies, while the conversion rate is the highest ever achieved by continuously operating, sub-100 fs lasers. The generated neutrons are emitted from an area of 0.65 cm 2 corresponding to the deuteron beam spot on the catcher. Their angular distribution is peaked in forward and backward directions in agreement with the literature data on the angular distribution of H 2 ( d , n ) 3 He reaction. The system operated continuously for several hours per day with an unprecedented stability of 5 %

    Proteomic profiling of serum small extracellular vesicles predicts post-COVID syndrome development

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    Post-COVID syndrome affects 10-35 % of COVID-19 patients, and up to 85 % of hospitalized individuals, underscoring the need for early identification of high-risk cases. We hypothesized that the proteomic profile of serum small extracellular vesicles (sEVs) obtained during acute SARS-CoV-2 infection could predict post-COVID syndrome. Serum samples from 59 patients, stratified as asymptomatic, moderate, or severe, were analyzed. sEVs were isolated, characterized by electron microscopy, nanoparticle tracking, and flow cytometry, then profiled via LC-MS. Classification models integrating comorbidities, acute symptoms, and sEV proteomics distinguished the three groups, with sEV data outperforming conventional measures. Of 620 identified proteins, 30 showed significant differences between symptomatic and asymptomatic patients, including 12 linked to complement activation. ELISA confirmed LC-MS results that serum sEVs of post-COVID patients had altered C1 inhibitor, C3, and C5 levels. These results suggest that sEV-based proteomics can enable earlier detection and more targeted follow-up for individuals at risk of post-COVID syndrome

    A2 Milk: The Impact of Genetic Variation in Milk Protein on Human Health

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    Recently, a new type of cow's milk has been commercialized in the markets, called A2 milk. It is derived from a specific allelic composition on chromosome 6. The only difference between A1 and A2 milk results from the polymorphism at the 67 amino acid chain. In this position, A2 milk has a proline amino acid, while A1 milk has a histidine amino acid. Proteins are one of the most important components of milk, especially casein, and have received significant attention as they are the source of bioactive opioid peptides called beta-casomorphin-7. Peptides are released through enzymatic digestion of casein and whey proteins. More precisely, this bioactive peptide is produced by sequential gastrointestinal digestion of bovine A1 variants proteins, while this phenomenon is not present in variant A2. Studies have reported that A1 milk can be harmful to health not only for adults but also for infants and that beta-casein A2 becomes a safer choice following the relationship between disease risk and consumption of the beta-casomorphin-7 peptide. Indeed, epidemiological studies suggest that the released beta-casomorphin-7 peptide is a risk factor for the development of diseases in humans, but this has not yet been validated by other studies. In contrast, A2 milk has been suggested as an appropriate substitute for A1 milk since populations consuming milk containing high levels of the A2 beta-casein variant have lower rates of diseases, such as diabetes, coronary heart disease, autism, and schizophrenia. Copyright© Bentham Science Publishers; For any queries, please email at [email protected]

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