Exosomes and microvesicles are two major categories of extracellular vesicles (EVs) released by almost all cell types and are highly abundant in biological fluids. Both the molecular composition of EVs and their release are thought to be strictly regulated by external stimuli. Multiple studies have consistently demonstrated that EVs transfer proteins, lipids and RNA between various cell types, thus mediating intercellular communication, and signaling. Importantly, small non-coding RNAs within EVs are thought to be major contributors to the molecular events occurring in the recipient cell. Furthermore, RNA cargo in exosomes and microvesicles could hold tremendous potential as non-invasive biomarkers for multiple disorders, including pathologies of the immune system. This mini-review is aimed to provide the state-of-the-art in the EVs-associated RNA transcriptome field, as well as the comprehensive analysis of previous studies characterizing RNA content within EVs released by various cells using next-generation sequencing. Finally, we highlight the technical challenges associated with obtaining pure EVs and deep sequencing of the EV-associated RNAs.
Participants of the study ESSE-RF-2 and co-authors: Moscow: Konstantinov V. V., Pokrovskaya M.S., Efimova I.A., Sivakova O.V.; Krasnodar: Alekseenko S.N., Gubarev S.V.; Оmsk: Livzan M.A., Grishechkina I.A., Rozhkova M.Yu.; Republic of Karelia: Vezikova N.N., Skopec I. S.; Ryazan: Filippov E.V., Dobrynina N.V., Nikulina N.N., Pereverzeva K.G., Moseychuk K.A.Aim. Evaluate the prevalence, awareness, treatment, and control of hypertension among people aged 25-64 examined in 4 regions of the Russian Federation. Material and methods. Study materials were the representative selections of non-organized male (n=3000) and female (n=3714) inhabitants of aged 25-64 from 4 regions of the Russian Federation (Krasnodar region, Omsk region, Ryazan region, the Republic of Karelia), response rate>80%. Systematic stratified multilevel random election was formed with locality criteria (Kisch method). All the participants were interviewed using the standard questionnaire. The universal epidemiological methods and evaluation criteria were used. The study was approved by the local ethics Committee of National research center for preventive medicine. Participants signed informed consent. Hypertension was defined as an average systolic blood pressure (SBP)≥140 mmHg and/or average diastolic blood pressure (DBP)≥90 mmHg and/or antihypertensive therapy (AHT). The efficacy of treatment was the achievement of the target BP. Control group – patients with BP<140/90 mmHg. Results. Mean SBP and DBP were 128.7±0,3 mmHg and 82.8±0.1 mmHg, respectively, higher BP was detected among male (p<0,001). The prevalence of hypertension was 44.2% that was higher among males than females (49.1% vs 39.9%, р˂0.0005), the highest hypertension frequency was in the Ryazan region. The awareness of hypertension was higher among females than in males 76.8% vs 69.4%. There were more persons with hypertension grade 1 among those, who were not aware of the hypertension. Medications were taken by 65.5% of females and 41.8% of males.Angiotensin-converting enzyme inhibitors were received by 49.9% of patients, angiotensin II receptor antagonists by 30.9%, beta blockers – 29.5%, diuretics – 22.7%, calcium antagonists – 15.7%, centrally acting drugs – 3.3%, others – 0.2%. The lack of AHT intake was negatively associated with age, ischemic heart disease, urban life and hypo-HDL especially among males. Heart rate >80 per min in females increased by 1.7 times the probability of absence of AHT. The prevalence of effectively treated was 49.7% of the participants with hypertension. The associations between ineffective treatment and abdominal obesity, ischemic heart disease (males), age, rural type of settlement, obesity (females) were found. Only 24.9% of patients had control of the hypertension.Conclusion. The prevalence of hypertension in Russian Federation remains high. An important task of the medical community is to identify the disease at an earlier stage of its development, before the appearance of complications. This approach can reduce the period from the onset of high blood pressure to a visit to the doctor.
Most common drug development failures originate from either bioavailability problems, or unexpected toxic effects. The culprit is often the liver, which is responsible for biotransformation of a majority of xenobiotics. Liver may be modeled using "liver on a chip" devices, which may include established cell lines, primary human cells, and stem cell-derived hepatocyte-like cells. The choice of biological material along with its processing and maintenance greatly influence both the device performance and the resultant toxicity predictions. Impediments to the development of "liver on a chip" technology include the problems with standardization of cells, limitations imposed by culturing and the necessity to develop more complicated fluidic contours. Fortunately, recent breakthroughs in the development of cell-based reporters, including ones with fluorescent label, permits monitoring of the behavior of the cells embed into the "liver on a chip" devices. Finally, a set of computational approaches has been developed to model both particular toxic response and the homeostasis of human liver as a whole; these approaches pave a way to enhance the in silico stage of assessment for a potential toxicity.
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