Although bone marrow-derived mesenchymal stromal cells (BM-MSCs) have been identified as a major cellular source of fibrosis, the exact molecular mechanism and signaling pathways involved have not been identified thus far. Here, we show that BM-MSCs contribute to fibrosis in myeloproliferative neoplasms (MPNs) by differentiating into αSMA-positive myofibroblasts. These cells display a dysregulated extracellular matrix with increased FN1 production and secretion of profibrotic MMP9 compared to healthy donor cells. Fibrogenic TGFβ and inflammatory JAK2/STAT3 and NFκB signaling pathway activity is increased in BM-MSCs of MPN patients. Moreover, coculture with mononuclear cells from MPN patients was sufficient to induce fibrosis in healthy BM-MSCs. Inhibition of JAK1/2, SMAD3 or NFκB significantly reduced the fibrotic phenotype of MPN BM-MSCs and was able to prevent the development of fibrosis induced by coculture of healthy BM-MSCs and MPN mononuclear cells with overly active JAK/STAT signaling, underlining their involvement in fibrosis. Combined treatment with JAK1/2 and SMAD3 inhibitors showed synergistic and the most favorable effects on αSMA and FN1 expression in BM-MSCs. These results support the combined inhibition of TGFβ and inflammatory signaling to extenuate fibrosis in MPN.
The study shows the relevance of sciatic nerve stiffness assessed by strain elastography using ARFI (Acoustic Radiation Force Impulse) for surgical decision making and the follow up of patients with deep gluteal syndrome (DGS). The research focuses on nerve stiffness associated with knee movements in order to determine the degree of nerve entrapment. Neurological examination, MRI of pelvis and electromyography (EMG) were performed as well. The sciatic nerve was scanned by ARFI (strain) elastography during knee movements in patients with DGS (143). In 54 patients surgical treatment was indicated, while 24 of them underwent surgery. The results were based on tissue response to ARFI by color elastogram and stiffness ratio. Diameters of the sciatic nerve in patients with DGS during knee flexion were statistically significantly lower than during extension movement (p<0.01).In patients with DGS (in ones without indication and the ones scheduled for surgery) sciatic nerve stiffness ratio was significantly increased (p<0.01) during knee flexion. Patients scheduled for surgery confirmed increased sciatic nerve stiffness during knee movements, compared with those without indications for surgery (p<0.05). Sciatic nerve recovery after surgery by diameter and stiffness ratio was marked (r=0.881). The correlation between MRI and EMG findings and ARFI nerve stiffness values in patients scheduled for surgery was high (r=0.963). The overall specificity of method was 93.5%, sensitivity was 88.9% with accuracy of 90.6%. ARFI elastography (by strain) is a diagnostic procedure based on nerve stiffness assessment and a useful tool in decision making for surgery and the follow up.
Apstrakt Uvod / Cilj rada: Sedalni živac (n. ischiadicus) je mešoviti živac koji nastaje u karlici od prednjih grana kičmenih (spinalnih) živaca od L4-S3. Tokom svog puta, n. ischiadicus može biti podložan pritisku u različitim regionima, a naročito u predelu zgloba
Background/Aim. The iliopsoas muscle originates from the Greek word ?psoa? meaning ?loin? and represents the only muscle in body that has anatomical preconditions for stability and movement of the trunk, pelvic and legs at the same time. The iliopsoas belongs to the inner thigh muscle group and forms part of the posterior abdominal wall. This muscle is the major flexor of the hip joint, and he is functionally essential for proper posture, walking, running and other physical activities. The aim of this study is to investigate the relationship between the anatomical parameters of the pelvis and femoral nerve, as well as the relationship of the same pelvic parameters and psoas major muscle. Methods. The study was conducted at the Faculty of Medicine, University of Belgrade. Our research was conducted on the cadaveric material on the Institute of Anatomy ?Niko Miljanic?, using 14 cadavers, of which they were 7. cadavers male and 7. cadavers female, aged 67-79 years. The measuring instruments used in this study were a ruler and an electronic digital caliper (measuring range 0-500 mm, 0.01 mm resolution). Statistical data processing was performed in SPSS 11.0 using Mann-Whitney U test. Results. Results of this study indicate that there is a significant statistical difference in pelvic width between male and female cadavers, which is observed in the reduction of the bituberal line in females, while the parameters of the bispinal line does not make significant difference between the two sexes. The decrease of the bituberal line in females was followed by an increase in the width of the proximal origin with a statistically significant decrease in the length of the proximal origin.of the psoas major muscle. Also the vertically distance of femoral nerve from the exit point of the muscle to the bispinal line was significantly reduced in the male group. Conclusion. Based on our results, we can assume that in most cases, due to the smaller bituberal and bispinal line, or narrower pelvis, a shorter proximal attachment of the psoas major muscle will occur with greater width (L2-L5 level) in female than in the male gender, resulting with a longer vertically distance of the femoral nerve. Such results indicate that there is a close correlation between the anatomical parameters of the psoas major muscle, wich may affect the distance of the femoral nerve exit from the muscle.
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