Adipocytes in the Uterine Wall during Experimental Healing and in Cesarean Scars during Pregnancy.

We have suggested that adipocytes in uterine scars may affect the development of the placenta accrete spectrum (PAS). In the experimental part, we explored adipocytes in the uterine wall by the twelfth sexual cycle after surgery. In the clinical part, we investigated adipocyte clusters in the cesarean scar of pregnant women with and without PAS. The uterine wall was evaluated in gross and histological sections using morphometry, histochemistry (hematoxylin and eosin stain, Mallory stain), and immunohistochemistry for FABP4 (adipocyte markers), CD68, CD163, CD206 (macrophages), CD 34 (endothelium), cytokeratin 8 (epithelium), aSMA (smooth muscle cells). The design included an experimental study on Sprague-Dawley rats (n = 18) after a full-thickness surgical incision on the seventh (n = 6), 30th (n = 6), and 60th day (n = 6). The clinical groups include pregnant women without uterine scars (n = 10), pregnant women with a uterine scar after previous cesarean sections (n = 10), and women with PAS (n = 11). Statistical processing was carried out using nonparametric methods. Comparisons were conducted using the Mann-Whitney U-test and Kruskal-Wallis test. Statistical significance was considered at p < 0.05. On the seventh day, the rat uterine horn was enveloped by adipose tissue, which contained crown-like structures with FABP4+, CD68+, CD206+, and CD163+ cells. FABP4+ cells in the uterine wall were absent by the 30th day. The number of CD206+ and CD163+ cells in the adipose tissue decreased by the 30th day. On the 60th day, the attachment of fat tissue was revealed in the form of single strands. The serous layer around the damaged area totally recovered on the 60th day. FABP4+ cells were not detected in the uterine wall samples from pregnant women without a previous cesarean section. Adipocytes were found in the scar during non-complicated pregnancy and with PAS. Reducing the number of CD68+ cells in adipocyte clusters, there were in myometrium with PAS. Increased CD206+ and CD163+ cells were revealed in uterine adipocyte clusters of the group. According to the experimental finding, adipocytes should be absent in the uterine wall by the 12th sexual cycle after a full-thickness surgical incision. The presence of adipocyte clusters in cesarean scar indicated the disturbance of cell interaction. Differences in the numbers of CD206 and CD163 cells in adipocyte clusters between groups with and without PAS may be indirect evidence that uterine adipocytes affect the development of PAS.

Hemostasis System and Plasminogen Activity in Retrochorial Hematoma in the First Trimester of Pregnancy.

(1) Background: The components of the fibrinolytic system and its main component, plasminogen, play a key role in the first months of pregnancy. The effect of autoantibodies interacting with plasminogen in the formation of retrochorial hematoma is unknown. The aim of our study was to determine the role of plasminogen and IgA, IgM, and IgG, which bind to plasminogen, in retrochorial hematoma. (2) Methods: Prothrombin time (PT), thrombin time (TT), partial activated thromboplastin time (aPTT), soluble fibrin-monomer complex (SFMC), D-dimer, plasminogen activity (%Plg), plasminogen concentration (Plg), and the levels of IgG (IgG-Plg), IgM (IgM-Plg), IgA (IgA-Plg) interacting with plasminogen were determined in plasma samples of 57 women with normal pregnancy and 16 with retrochorial hematoma. (3) Results: %Plg in plasma samples from women with retrochorial hematoma was significantly lower than in plasma samples from women with normal pregnancy. The diagnostic significance of %Plg in the ROC analysis was AUC = 0.85. A direct correlation was found between aPTT and the level of autologous IgM interacting with plasminogen. (4) Conclusions: A decrease in the activity of plasminogen in the blood serum of women in the first trimester of pregnancy may indicate disturbances in the hemostasis system and the formation of retrochorial hematoma. According to the results of the study, it is possible to recommend the determination of plasminogen activity in the management of pregnant women in gynecological practice.

Proteolyzed Variant of IgG with Free C-Terminal Lysine as a Biomarker of Prostate Cancer.

The differential diagnosis of prostate cancer is problematic due to the lack of markers with high diagnostic accuracy. We previously demonstrated the increased binding of IgG to human plasminogen (PLG) in plasma of patients with prostate cancer (PC) compared to healthy controls. Heavy and light chains of PLG (PLG-H and PLG-L) were immobilized on 96-well plates and the binding of IgG to PLG-H and PLG-L was analyzed in serum from 30 prostate cancer (PC) patients, 30 patients with benign prostatic hyperplasia (BPH) and 30 healthy controls using enzyme-linked immunosorbent assay (ELISA). Our results demonstrate that IgG from PC sera bind to PLG-H but not to PLG-L. This interaction occurred through the free IgG C-terminal lysine (Lys) that becomes exposed as a result of IgG conformational changes associated with proteolysis. Circulating levels of modified IgG with exposed C-terminal Lys (IgG-Lys) were significantly higher in PC patients than in healthy controls and in BPH. We used Receiver Operating Characteristic (ROC) analysis to calculate the sensitivity (SN) and specificity (SP) of circulating IgG-Lys for differentiating PC from BPH as 77% and 90%, respectively. The area under the curve (AUC) was 0.87. We demonstrated that the diagnostic accuracy of circulating levels of IgG-Lys is much higher than diagnostic accuracy of total PSA (tPSA).

Quantification of autoantibodies to plasminogen in plasma of patients with cancer.

BACKGROUND: The investigation of autoantibodies which may play a role in the processes of angiogenesis and tumorogenesis is important in the early diagnostis of cancer. OBJECTIVE: This study aimed to investigate the levels of autoantibodies to Glu-plasminogen (Pg) in plasma of patients with tumors. METHODS: Plasma samples from healthy volunteers were compared with samples from patients with prostate cancer using 2D electrophoresis and MALDI-TOF mass spectrometry. Plasma samples from 25 patients with prostate cancer, 15 patients with benign prostatic hyperplasia (BPH), 29 patients with breast cancer, and 43 healthy volunteers were tested using ELISA to anti-Pg IgG autoantibodies. Affinity chromatography on Pg-sepharoses was used to assess the quantity of anti-Pg IgG in control plasma and plasma of prostate cancer patients. ATTESTAT program was used for nonparametric analysis. RESULTS: Using 2D electrophoresis, marker spots below 50 kD were detected in prostate cancer samples. These spots were identified as fragments of Pg and IgG. Using affinity chromatography on Pg-sepharose, the quantity of IgG bound to Pg versus total IgG was determined to be 9% in control and 27% in prostate cancer samples. The frequency of occurence of elevated levels of anti-Pg IgG was 84% in prostate cancer samples, 69% in breast cancer samples, 40% in BPH samples, and 11% in healthy plasma. CONCLUSIONS: Autoantibodies to Pg may be involved in tumorogenesis and elevated levels of anti-Pg IgG antibodies may be a risk factor for tumor development.