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Autologous stem cell therapy is the most promising alternative treatment in patients with chronic ischemic diseases, including ischemic heart disease and critical limb ischemia, which are characterized by poor prognosis related to serious impair of quality of life, high risk of cardiovascular events and mortality rates. However, one of the most serious shortcomings of stem cell transplantation are low survival after transplantation to the site of injury, as large number of stem cells are lost within 24 hours after delivery. Multiple studies suggest that combination of lipidlowering drugs, statins, and stem cell transplantation might improve therapeutic efficacy in regenerative medicine. Statins are inhibitors of HMG-CoA reductase and belong to recommended therapy in all patients suffering from critical limb ischemia. Statins possess non-lipid effects which involve improvement of endothelial function, decrease of vascular inflammation and oxidative stress, anti-cancer and stem cell modulation capacities. These non-lipid effects are explained by inhibition of mevalonate synthesis via blocking isoprenoid intermediates synthesis, such as farnesylpyrophospate and geranylgeranylpyrophospate and result in modulation of the PI3K/Akt pathway. Moreover, statin-mediated microRNA regulation may contribute to the pleiotropic functions. MicroRNA interplay in gene regulatory network of IGF/Akt pathway may be of special significance for the treatment of critical limb ischemia. We assume further studies are needed for detailed analysis of statin interactions with microRNA at the molecular level and their link to PI3K/Akt and IGF/Akt pathway in stem cells, which are currently the most promising treatment strategy used in chronic ischemic diseases. [ABSTRACT FROM AUTHOR]

Hospitalized patients in internal medicine have an increased risk of low physical reserve which further declines during the hospital stay. The diagnosis requires bed-side testing of functional domains or more complex investigations of the muscle mass. Clinically useful biomarkers of functional status are needed, thus we aimed to explore the potential of microRNAs. Among hospitalized patients, we recorded the basic demographics, anthropometrics, nutritional status, and physical function domains: hand-grip strength (HGS, abnormal values M<30 kg, W<20 kg), balance (<30 s), chair-stands speed (CHSS<0.5/s) and gait speed (GS<0.8 m/s). A panel of five micro-RNAs (miRNA 1, miRNA 133a, miRNA 133b, miRNA 29a, miRNA 29b) and basic blood biochemistry and vitamin D values were recorded. We enrolled 80 patients (M40, W40), with a mean age of 68.8± 8.4 years. Obesity was observed in 27.5 % and 30 %, low HGS and low CHSS in 65.0, 77.5 %, and 80, 90 % of men and women respectively. The median hospital stay was 6.5 days. MiRNA29a and miRNA29b have the strongest correlation with the triceps skinfold (miRNA 29b, r=0.377, p=0.0006) and CHSS (miRNA 29a, r=0.262, p=0.02). MiRNA 29a, miRNA 29b and 133a levels were significantly higher in patients with CHSS<0.5/s. Other anthropometric parameters, mobility domains, or vitamin D did not correlate. All miRNAs except of miRNA 1, could predict low CHSS (miRNA29b, AUROC=0.736 CI 0.56-0.91, p=0.01), particularly in patients with low HGS (miRNA 29b, AUROC=0.928 CI 0.83-0.98). Among hospitalized patients in internal medicine, low functional status was frequent. MicroRNAs were fair biomarkers of the antigravity domain, but not other domains. Larger studies with clinical endpoints are needed. [ABSTRACT FROM AUTHOR]

Sarcopenia is defined as an age-associated loss of skeletal muscle function and muscle mass and is common in older adults. Sarcopenia as a disease is currently of interest not only to orthopedists and surgeons but also to internists, endocrinologists, rheumatologists, cardiologists, diabetologists, gynaecologists, geriatricians and paediatricians. In cooperation with the 5th Internal Medicine Clinic, we, as a unit of clinical research, aimed to describe a sarcopenic specific miRNA expression profile for disease diagnostics and classification of the severity of muscle performance deterioration. This study included a total of 80 patients (age 55-86 years) hospitalized at the V. Internal medicine clinic of LFUK and UNB with different severity of muscle performance deterioration. The study participants were evaluated and classified according to short physical performance battery score (SPPB). In this study, we investigated the role of circulating miRNAs in sarcopenia in the elderly. We hypothesized that sarcopenia effects the expression of muscle tissue-specific miRNAs (MyomiRNAs), which could be potentially reflected in the blood plasma miRNA expression profile. The expression of specific circulating miRNAs in patients with different muscle performances was analyzed. Patients' blood plasma was evaluated for the expression of myomiRNAs: miRNA-29a, miRNA-29b, miRNA-1, miRNA-133a, miRNA-133b, miRNA-206, miRNA-208b and miRNA-499, and the data were correlated with diagnostic indicators of the disease. We showed a specific sarcopenia miRNA profile that could be considered a possible biomarker for the disease. Patients with low muscle performance showed increased miRNA-1, miRNA-29a and miRNA-29b expression and decreased for the miRNA-206, miRNA-133a, miRNA-133b, miRNA-208b and miRNA-499 expression. We show that the severity of muscle performance deterioration in sarcopenia correlates with specific miRNA expression. We also propose the profile of miRNAs expression in blood plasma as a specific biomarker for sarcopenia diagnostics. Future clinical studies will be necessary to eventually naturally have to elucidate the underlined molecular mechanism responsible for specific miRNAs expression in sarcopenia pathology and progression of the disease. [ABSTRACT FROM AUTHOR]

Systematic physical activity increases physical fitness and exercise capacity that lead to the improvement of health status and athletic performance. Considerable effort is devoted to identifying new biomarkers capable of evaluating exercise performance capacity and progress in training, early detection of overtraining, and monitoring health-related adaptation changes. Recent advances in OMICS technologies have opened new opportunities in the detection of genetic, epigenetic and transcriptomic biomarkers. Very promising are mainly small non-coding microRNAs (miRNAs). miRNAs post-transcriptionally regulate gene expression by binding to mRNA and causing its degradation or inhibiting translation. A growing body of evidence suggests that miRNAs affect many processes and play a crucial role not only in cell differentiation, proliferation and apoptosis, but also affect extracellular matrix composition and maintaining processes of homeostasis. A number of studies have shown changes in distribution profiles of circulating miRNAs (c-miRNAs) associated with various diseases and disorders as well as in samples taken under physiological conditions such as pregnancy or physical exercise. This overview aims to summarize the current knowledge related to the response of blood c-miRNAs profiles to different modes of exercise and to highlight their potential application as a novel class of biomarkers of physical performance capacity and training adaptation. [ABSTRACT FROM AUTHOR]