Interrelation between miRNAs Expression Associated with Redox State Fluctuations, Immune and Inflammatory Response Activation, and Neonatal Outcomes in Complicated Pregnancy, Accompanied by Placental Insufficiency

Redox disbalance in placental cells leads to the hyperproduction of reactive oxygen species (ROS), it mediates the dysregulation of the maternal immune tolerance to a semi-allogenic fetus, inducing pro-inflammatory reactions, and it plays a central role in perinatal complications and neonatal disease programming. Microvesicles, which provide transplacental communication between a mother and fetus, contain microRNAs (miRNAs) that are sensitive to oxidative stress (OS) mediators and can control the balance of ROS production and utilization in target cells. In the context of this paradigm, we evaluated the markers of redox balance—MDA and 4-HNE for OS and GPx, and SOD, CAT, and GSH for the antioxidant system in the cord blood plasma of newborns diagnosed with fetal growth restriction (FGR)—by using polarography, spectrophotometry, and Western blotting. The expression of miRNAs associated with OS, immune and inflammatory responses in the blood plasma of newborns with intrauterine pneumonia (IP), neonatal sepsis (NS) and respiratory distress syndrome (RDS) was evaluated by a quantitative RT-PCR. Significant differences in the MDA level and reduced GPx and CAT activity were co-found for early-onset FGR (i.e., p ≤ 0.03 and >32 GA; p ≤ 0.009), IP (>32 GA; p ≤ 0.0001), and RDS (>32 GA; p ≤ 0.03). At the same time, the expression of miR-25-3p (p ≤ 0.03) was increased only in newborns with NS (>32 GA; p ≤ 0.03). The risk of developing IVH for premature newborns with IP (AUC = 0.8; cutoff—0.6) and NS (AUC = 0.68; cutoff—0.49) was assessed based on the miR-25-3p and miR-127-3p expression. Several key transcription factors were identified as the targets of studied miRNA since they are involved in the regulation of OS (NRF2), signaling and activation of the immune response (PRDM1, CCL26) and, also, inflammatory responses (NFKB1). The study of these miRNAs showed that they are involved in the modulation of processes leading to perinatal complications. Moreover, miR-127-3p is related to pro-inflammatory reactions and the formation of the macrophage phenotype in newborns with IP, NS, and RDS, while miR-25-3p is associated with an inhibition of macrophage migration and activation of antioxidant enzymes, which may prevent the development of oxidative damage in newborns with NS

Endometriosis in Adolescents: Diagnostics, Clinical and Laparoscopic Features

Background: The early diagnosis of endometriosis in adolescents is not developed. Objective: We aim to conduct clinical, imaging, laparoscopic and histological analyses of peritoneal endometriosis (PE) in adolescents in order to improve early diagnosis. Methods: In total, 134 girls (from menarche to 17 years old) were included in a case–control study: 90 with laparoscopically (LS) confirmed PE, 44 healthy controls underwent full examination and LS was analyzed in the PE group. Results: Patients with PE were characterized with heredity for endometriosis, persistent dysmenorrhea, decreased daily activity, gastrointestinal symptoms, higher LH, estradiol, prolactin and Ca-125 (<0.05 for each). Ultrasound detected PE in 3.3% and MRI in 78.9%. The most essential MRI signs are as follows: hypointense foci, the heterogeneity of the pelvic tissue (paraovarian, parametrial and rectouterine pouch) and sacro-uterine ligaments lesions (<0.05 for each). Adolescents with PE mostly exhibit initial rASRM stages. Red implants correlated with the rASRM score, and sheer implants correlated with pain (VAS score) (<0.05). In 32.2%, foci consisted of fibrous, adipose and muscle tissue; black lesions were more likely to be histologically verified (0.001). Conclusion: Adolescents exhibit mostly initial PE stages, which are associated with greater pain. Persistent dysmenorrhea and detected MRI parameters predict the laparoscopic confirmation of initial PE in adolescents in 84.3% (OR 15.4; <0.01), justifying the early surgical diagnostics and shortening the time delay and suffering of the young patients

Mitoregulin Contributes to Creatine Shuttling and Cardiolipin Protection in Mice Muscle

Small peptides compose a large share of the mitochondrial proteome. Mitoregulin (Mtln) is a mitochondrial peptide known to contribute to the respiratory complex I functioning and other processes in mitochondria. In our previous studies, we demonstrated that Mtln knockout mice develop obesity and accumulate triglycerides and other oxidation substrates in serum, concomitant with an exhaustion of tricarboxylic acids cycle intermediates. Here we examined the functional role of Mtln in skeletal muscles, one of the major energy consuming tissues. We observed reduced muscle strength for Mtln knockout mice. Decrease of the mitochondrial cardiolipin and concomitant increase in monolysocardiolipin concentration upon Mtln inactivation is likely to be a consequence of imbalance between oxidative damage and remodeling of cardiolipin. It is accompanied by the mitochondrial creatine kinase octamer dissociation and suboptimal respiratory chain performance in Mtln knockout mice