In the global context, the epidemic of breast cancer (BC) is evident for the early 21st century. Evidence shows that national mammography screening programs have sufficiently reduced BC related mortality. Therefore, the great utility of the mammography-based screening is not an issue. However, both false positive and false negative BC diagnosis, excessive biopsies, and irradiation linked to mammography application, as well as sub-optimal mammography-based screening, such as in the case of high-dense breast tissue in young females, altogether increase awareness among the experts regarding the limitations of mammography-based screening. Severe concerns regarding the mammography as the “golden standard” approach demanding complementary tools to cover the evident deficits led the authors to present innovative strategies, which would sufficiently improve the quality of the BC management and services to the patient. Contextually, this article provides insights into mammography deficits and current clinical data demonstrating the great potential of non-invasive diagnostic tools utilizing circulating miRNA profiles as an adjunct to conventional mammography for the population screening and personalization of BC management.
Why does healthcare of breast cancer (BC) patients, especially in a young population, matter and why are innovative strategies by predictive, preventive, and personalized medicine (PPPM) strongly recommended to replace current reactive medical approach in BC management? Permanent increase in annual numbers of new BC cases with particularly quick growth of premenopausal BC patients, an absence of clearly described risk factors for those patients, as well as established screening tools and programs represent important reasons to focus on BC in young women. Moreover, "young" BC cases are frequently "asymptomatic", difficult to diagnose, and to treat effectively on time. The objective of this article is to update the knowledge on BC in young females, its unique molecular signature, newest concepts in diagnostics and therapy, and to highlight the concepts of predictive, preventive, and personalized medicine with a well-acknowledged potential to advance the overall disease management.
In contrast to the genetic component in mammary carcinogenesis, epigenetic alterations are particularly important for the development of sporadic breast cancer (BC) comprising over 90% of all BC cases worldwide. Most of the DNA methylation processes are physiological and essential for human cellular and tissue homeostasis, playing an important role in a number of key mechanisms. However, if dysregulated, DNA methylation contributes to pathological processes such as cancer development and progression. A global hypomethylation of oncogenes and hypermethylation of tumor-suppressor genes are characteristic of most cancer types. Moreover, histone chemical modifications and non-coding RNA-associated multi-gene controls are considered as the key epigenetic mechanisms governing the cellular homeostasis and differentiation states. A number of studies demonstrate dietary plant products as actively affecting the development and progression of cancer. BNutri-epigenetics^focuses on the influence of dietary agents on epigenetic mechanisms. This approach has gained considerable attention; since in contrast to genetic alterations, epigenetic modifications are reversible affect early carcinogenesis. Currently, there is an evident lack of papers dedicated to the phytochemicals/plant extracts as complex epigenetic modulators, specifically in BC. Our paper highlights the role of plant natural compounds in targeting epigenetic alterations associated with BC development, progression, as well as its potential chemoprevention in the context of preventive medicine. Comprehensive measures are stated with a great potential to advance the overall BC management in favor of predictive, preventive, and personalized medical services and can be considered as Bproof-of principle^model, for their potential application to other multifactorial diseases.
Several relatively recently published studies have shown changes in plasma metabolites in various viral diseases such as Zika, Dengue, RSV or SARS-CoV-1. The aim of this study was to analyze the metabolome profile of patients during acute COVID-19 approximately one month after the acute infection and to compare these results with healthy (SARS-CoV-2-negative) controls. The metabolome analysis was performed by NMR spectroscopy from the peripheral blood of patients and controls. The blood samples were collected on 3 different occasions (at admission, during hospitalization and on control visit after discharge from the hospital). When comparing sample groups (based on the date of acquisition) to controls, there is an indicative shift in metabolomics features based on the time passed after the first sample was taken towards controls. Based on the random forest algorithm, there is a strong discriminatory predictive value between controls and different sample groups (AUC equals 1 for controls versus samples taken at admission, Mathew correlation coefficient equals 1). Significant metabolomic changes persist in patients more than a month after acute SARS-CoV-2 infection. The random forest algorithm shows very strong discrimination (almost ideal) when comparing metabolite levels of patients in two various stages of disease and during the recovery period compared to SARS-CoV-2-negative controls.
Background: COVID-19 represents a severe inflammatory condition. Our work was designed to monitor the longitudinal dynamics of the metabolomic response of blood plasma and to reveal presumable discrimination in patients with positive and negative outcomes of COVID-19 respiratory symptoms. Methods: Blood plasma from patients, divided into subgroups with positive (survivors) and negative (worsening condition, non-survivors) outcomes, on Days 1, 3, and 7 after admission to hospital, was measured by NMR spectroscopy. Results: We observed changes in energy metabolism in both groups of COVID-19 patients; initial hyperglycaemia, indicating lowered glucose utilisation, was balanced with increased production of 3-hydroxybutyrate as an alternative energy source and accompanied by accelerated protein catabolism manifested by an increase in BCAA levels. These changes were normalised in patients with positive outcome by the seventh day, but still persisted one week after hospitalisation in patients with negative outcome. The initially decreased glutamine plasma level normalised faster in patients with positive outcome. Patients with negative outcome showed a more pronounced Phe/Tyr ratio, which is related to exacerbated and generalised inflammatory processes. Almost ideal discrimination from controls was proved. Conclusions: Distinct metabolomic responses to severe inflammation initiated by SARS-CoV-2 infection may serve towards complementary personalised pharmacological and nutritional support to improve patient outcomes.
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