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.
VIEWS 2870
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.
VIEWS 2846
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.
VIEWS 2919