Circulating microRNAs (c-microRNAs, c-miRNAs), which are present in almost all biological fluids, are promising sensitive biomarkers for various diseases (oncological and cardiovascular diseases, neurodegenerative pathologies, etc.), and their signatures accurately reflect the state of the body. Studies of the expression of microRNA markers show that they can enable a wide range of diseases to be diagnosed before clinical symptoms are manifested, and they can help to assess a patient’s response to therapy in order to correct and personalize treatments. This review discusses the latest trends in the uses of miRNAs for diagnosing and treating various diseases, viral and non-viral. It is concluded that exogenous microRNAs can be used as high-precision therapeutic agents for these purposes.

Calix[4]arenes bearing two or four methylenebisphosphonic acid groups at the macrocyclic upper rim have been studied with respect to their effects on fibrin polymerization. The most potent inhibitor proved to be calix[4]arene tetrakis‐methylene‐bis‐phosphonic acid (C‐192), in which case the maximum rate of fibrin polymerization in the fibrinogen + thrombin reaction decreased by 50% at concentrations of 0.52 × 10⁻⁶ m (IC₅₀). At this concentration, the molar ratio of the compound to fibrinogen was 1.7 : 1. For the case of desAABB fibrin polymerization, the IC₅₀ was 1.26 × 10⁻⁶ m at a molar ratio of C‐192 to fibrin monomer of 4 : 1. Dipropoxycalix[4]arene bis‐methylene‐bis‐phosphonic acid (C‐98) inhibited fibrin desAABB polymerization with an IC₅₀ = 1.31 × 10⁻⁴ m. We hypothesized that C‐192 blocks fibrin formation by combining with polymerization site ‘A’ (Aα17–19), which ordinarily initiates protofibril formation in a ‘knob‐hole’ manner. This suggestion was confirmed by an HPLC assay, which showed a host–guest inclusion complex of C‐192 with the synthetic peptide Gly‐Pro‐Arg‐Pro, an analogue of site ‘A’. Further confirmation that the inhibitor was acting at the initial step of the reaction was obtained by electron microscopy, with no evidence of protofibril formation being evident. Calixarene C‐192 also doubled both the prothrombin time and the activated partial thromboplastin time in normal human blood plasma at concentrations of 7.13 × 10⁻⁵ m and 1.10 × 10⁻⁵ m, respectively. These experiments demonstrate that C‐192 is a specific inhibitor of fibrin polymerization and blood coagulation and can be used for the design of a new class of antithrombotic agents.

Using the idea of "proline brackets" we have found four sites in fibrin amino acid sequence, and appropriate peptides were synthesized: γ69NPDESSKPN77, Bβ228QPDSSVKPY236, Bβ455RPFFPQ460 and Aα195LPSRDRQHLPL205. Turbidity and electron-microscopy analyses have demonstrated that synthetic peptide Aα195-205 specifically inhibited the stage of fibrin protofibril formation and peptide γ69-77 - the stage offibrin protofibril lateral association. The data obtained testify that there are the sites involved in these processes in the appropriate amino acid sequences of fibrin molecule.

A series of hydroxycalix[4]arenes bearing one, two, or four fragments of methylenebisphosphonic acids was synthesized by the reaction of appropriate formylcalixarenes with sodium salts of dialkylphosphites. These calixarenes inhibit specifically 50% of fibrin polymerization in the fibrinogen + thrombin reaction as well as monomeric fibrin desAABB polymerization in concentration up to 0.5 × 10⁻⁶ M.

Отримано моноклональнi антитiла (монАТ) класу IgG2а, епiтоп для яких знаходиться в дiлянцi Е3-фрагмента фiбрину А 20–78. Турбiдиметричним методом аналiзу встановлено, що данi монАТ та їх Fab-фрагменти iнгiбують процес полiмеризацiї фiбрину. Методом т-IФА встановлено, що монАТ реагують з фiбриногеном, фiбрином та його Е3-фрагментом, однак не реагують з (DD)E-комплексом, в якому реалiзована взаємодiя центрiв полiмеризацiї “А”–”а”, що, очевидно, екранує зону епiтопу А 20–78.

Дослiджено вплив монАТ II-5с, епiтоп якого локалiзований в Aα20–78 фрагментi Е-регiону молекули фiбриногену, на експозицiю неоантигенної детермiнанти монАТ I-3с у ходi трансформацiї фiбриногену в фiбрин. Iз застосуванням IФ, ППР й електрофоретичного аналiзу встановлено, що монАТ II-5с iнгiбує зв’язування монАТ I-3с з фiбрином, тромбiну з фiбрином i вiдщеплення фiбринопептиду А вiд фiбриногену в системах фiбриноген+тромбiн i Х-фрагмент фiбриногену+тромбiн. Цi данi пiдтверджують нашу гiпотезу про тромбiн-фiбриногеновий субстратний комплекс як тригер структурної перебудови Е-регiонiв молекули фiбриногену, що супроводжується формуванням у Bβ126–135 дiлянцi фiбрину неоантигенної детермiнанти монАТ I-3с.