Psoralens are medicinal photosensitizing furocoumarins which are used in photochemotherapy and photoimmunotherapy of dermatoses. Psoralen photooxidation products may be involved in therapeutic effects, but the possible mechanisms of their action remain unclear. The study was aimed to assess the prospective pharmacological effects and mechanisms of activity for six previously identified ortho–hydroxyformyl-containing psoralen photooxidation products and their cycloadducts with aminothiols, as well as for structurally similar compounds (furocoumaric acid and tucaresol). Chemoinformatic analysis of the prospective pharmacological effects and mechanisms of action of these compounds was performed using the PASS and PharmaExpert software. The predicted pharmacological effects partially confirmed by previous studies highlight the possible involvement of psoralen photooxidation products in the effects of PUVA therapy or photopheresis during the course of dermatoses and proliferative disorders treatment. A broad spectrum of pharmacological effects found for furocoumaric acid and cycloadducts of coumarinic and benzofuranic photoproducts of psoralen with cysteine and homocysteine appoints new directions of research relating to therapeutic use of psoralens.
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Dislocation of the acetabular component is one of the most frequent complications of total hip arthroplasty. It is commonly attributed to implant malpositioning. However, not all dislocations can be explained by this hypothesis. The aim of our study was to elucidate the role of intraoperative injury to hip abductors (m. gluteus minimus in the first place, since it is reportedly an important hip stabilizer) in the development of postoperative hip dislocation. The experiment was conducted in 4 male and 3 female cadavers. A total of 12 THA were performed. The Hardinge and Watson-Jones approaches were used in equal proportion. On plain radiography, acetabular inclination was 40–47°, anteversion was 10–22°; technically and biomechanically, these values were within the normal range and did not depend on the type of surgical approach (for inclination, p = 0.94; for anteversion, p = 0.63), ruling out implant malpositioning as a risk factor for hip dislocation. Nevertheless, implant stability was significantly disrupted following transection of the anterior or posterior fascicle of m. gluteus minimus, leading to the dislocation of the acetabular component in standard rotation and flexion tests. Thus, our study shows the significant role of m. gluteus minimus in stabilizing the hip joint. Preservation or adequate repair of this muscle during surgery will reduce the risk or dislocation and help to restore the anatomy and biomechanics of the operated joint.
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The search for the optimal cell model for studying the pathogenesis of pathological scars is a pressing challenge. This study aimed at evaluating the feasibility of using telomerized fibroblasts for the in vitro 3D modeling of pathological hypertrophic scars. NF and Fb-hTERT cells were cultured as monolayers and spheroids in the absence and in the presence of TGFβ1. The metabolic activity of the cultured cells was assessed using the MTT assay. Cell migration was estimated using the scratch assay. The expression of genes associated with fibrous scar tissue growth was measured by qRT-PCR. Fb-hTERT cells were more metabolically active than NF cells in the presence of TGFβ1 (for 1 ng/ml: 179 ± 12% vs. 135 ± 13% respectively; p < 0,05). Spheroids grown from Fb-hTERT cells were significantly larger than those derived from NF cells. In the presence of TGFβ1, the expression of proteins associated with extracellular matrix production (COL1A1, COL3A1, FN1) was lower in Fb-hTERT cells than in NF cells (more than 25, 20 and 2-fold, respectively; p < 0.05). Intact NF cells were more active in closing the scratch than Fb-hTERT cells: on day 2, the gap closure rate was 2.28 times higher in NF cells (p < 0.05). Exposure to TGFβ1 stimulated Fb-hTERT, unlike NF cells, to close the gap 2 times faster on day 2 (p < 0.05). Thus, telomerized fibroblasts have a few phenotypic traits observed in keloid fibroblasts; still there are some limitations that should be accounted for when using Fb-hTERT cells for the modeling of pathological hypertrophic scars.
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Transcranial magnetic stimulation (TMS) is one of rehabilitation approaches for patients with chronic disorders of consciousness (DOC). The aim of our study was to assess neurotrophic factors and the changes of those after TMS course in patients with chronic DOC. We enrolled 26 patients with chronic DOC of various etiology and 21 heathy volunteers. Blood serum and cerebrospinal fluid (CSF) were collected from all patients before and after the TMS course, the levels of BDNF, NSE, NGF, РDGF, GDNF and NT3 were assessed in the biomaterial. The blood BDNF, NSE, PDGF, GDNF and NT3 in patients with chronic DOC were higher compared to healthy volunteers (p < 0.05). We found no correlations between the type of DOC and neurotrophic factors concentrations in blood and CSF. The CSF level of BDNF in patients after traumatic brain injury (TBI) was higher compared to patients with non-traumatic chronic DOC (p < 0.05). We also found the increase of CSF BDNF after the TMS course in patients after TBI (p < 0.05). No other significant differences between groups and another blood and cerebrospinal fluid biomarker levels were detected. Thus, the serum BDNF, NSE, PDGF, GDNF and NT3 levels in patients with chronic DOC were higher compared to healthy volunteers. The BDNF level in CSF was higher in patients with traumatic DOC, and it also increased after the course of high-frequency TMS in this group. This fact may indicate the long-term neuronal plasticity processes in patients after TBI, as well as more favorable rehabilitation prognosis.
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One of the currently assumed causes of impaired social interaction exhibited by children with autism spectrum disorders (ASD) is dysfunction of the mirror neuron system (MNS), which is responsible for imitation, understanding the intentions and emotions of other people. Desynchronization of sensorimotor rhythms is considered to be the indicator of MNS activation. This study aimed to analyze the specific patterns of reactivity of the μ-rhythm in an individually determined frequency range and β-rhythm on the EEG in children with ASD during independent movements, observation, imitation and auditory perception of similar movements performed by another person. The data collected were compared to those describing normally developing children. The study involved right-handed children with ASD aged 5–10 (n = 10) and normally developing children (n = 10). In the independent movements exercise, β-rhythm desynchronization was more pronounced in children with ASD, with difference becoming significant in the P4 locus (p = 0.03). In the movements imitation exercise, the groups showed significant differences in the EEG μ-rhythm in the locus C3 (p = 0.03). Auditory perception of movements revealed significant differences in the ranges of both μ-rhythm (loci F3 and Fz (p = 0.02), F4 (p = 0.04), Cz (p = 0.009)) and β-rhythm (loci Fz (p = 0.01), F4 (p = 0.02)). In these situations, children with ASD exhibited synchronization of sensorimotor rhythms, while normally developing children showed desynchronization. The assumption is that the specific patterns revealed are the consequences of disruption of functions of MNS and anti-mirror system. The data obtained can be used in development of EEG biofeedback training protocols for children with ASD.
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 Antiviral system of innate immunity includes two main components: the mitochondrial antiviral sensor — the mitochondrial outer membrane protein and peripheral blood neutrophils capable of forming neutrophilic extracellular traps. Depending on the activation pathway of the mitochondrial antiviral sensor (MAVS), two possible variants of cells death, apoptosis or cellular degeneration with necrotic changes, develop during cell infection with an RNA-containing virus. The development of virus-induced apoptosis of infected cells causes the formation of neutrophilic extracellular traps, the secretion of inflammatory cytokines, ROS generation, tissue damage, hemocoagulation and the development of an acute inflammatory process with the development of COVID-19 pneumonia. Violation of the prion-like reaction of MAVS in response to viral infection of the cell triggers an alternative pathway for activating autophagy. Cells under conditions of prolonged activation of autophagy experience necrotic changes and are eliminated from the organism by monocytes/macrophages that secrete anti-inflammatory cytokines. This type of reaction of the antiviral system of innate immunity corresponds to the asymptomatic course of the disease. From the most significant aspects of the pathogenesis of the coronavirus infection COVID-19 given, recommendations for the prophylactic treatment of this dangerous disease follow. The proposed treatment can significantly decrease the severity of COVID-19 disease and reduce mortality.
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