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.

The potential of miR-153 as aggressive prostate cancer biomarker.

Introduction: Prostate cancer (PC) is one of the most frequently diagnosed cancers in males. MiR-153, as a member of the microRNA (miRNA) family, plays an important role in PC. This study aims to explore the expression and possible molecular mechanisms of the miR-153 action. Methods: Formalin-fixed paraffin-embedded (FFPE) tissues were collected from prostatectomy specimens of 29 metastatic and 32 initial stage PC patients. Expression levels of miR-153 were measured using real-time reverse transcription polymerase chain reaction (qRT-PCR). 2-ΔΔCT method was used for quantitative gene expression assessment. The candidate target genes for miR-153 were predicted by TargetScan. Mutations in target genes of miR-153 were identified using exome sequencing. Protein-protein interaction (PPI) networks, Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to investigate the potential molecular mechanisms of miR-153 in PC. Results: MiR-153 was significantly up-regulated in PC tissues compared to non-cancerous tissues. The analysis of correlation between the expression level of miR-153 and clinicopathological factors revealed a statistically significant correlation with the stage of the tumor process according to tumor, node, metastasis (TNM) staging system (p = 0.0256). ROC curve analysis was used to evaluate the predictive ability of miR-153 for metastasis development and it revealed miR-153 as a potential prognostic marker (AUC = 0.85; 95%CI 0.75-0.95; sensitivity = 0.72, specificity = 0.86)). According to logistic regression model the high expression of miR-153 increased the risk of metastasis development (odds ratios = 3.14, 95% CI 1.62-8.49; p-value = 0.006). Whole exome sequencing revealed nonsynonymous somatic mutations in collagen type IV alpha 1 (COL4A1), collagen type IV alpha 3 (COL4A3), forkhead box protein O1 (FOXO1), 2-hydroxyacyl-CoA lyase 1 (HACL1), hypoxia-inducible factor 1-alpha (HIF-1A), and nidogen 2 (NID2) genes. Moreover, KEGG analysis revealed that the extracellular matrix-receptor (ECM-receptor) interaction pathway is mainly involved in PC. Conclusion: MiR-153 is up-regulated in PC tissues and may play an important role in aggressive PC by targeting potential target genes.

Severe complications of chronic cholelithiasis treatment.

BACKGROUND: Gallstone disease is a burden affecting about 15% percent of the population around the world. The complications of gallstone disease are numerous and many require emergency care. Severe complications are not uncommon and require special attention, as lethal outcome is possible. CASE PRESENTATION: We present a retrospective analysis of eight cases describing severe complications of gallstones in patients undergoing endoscopic treatment of chronic gallstones conditions. All patients were admitted to our emergency care department following symptoms onset. The diagnostic difficulties, treatment strategies and outcomes are presented. The associated risk factors and preventative measures are discussed. Two patients developed profuse bleeding, two developed acute pancreatitis, two patients had perforation related complications. One rare case of bilioma and one case of iatrogenic injury are presented. All patients had severe condition, in two cases lethal outcome was a result of co-morbidity and difficulties in management. CONCLUSION: Special care should be taken in patients with risk factors of severe complications in order to improve outcome and prevent the development of life-threatening conditions.

Bacterial hepatocyte growth factor receptor agonist stimulates hepatocyte proliferation and accelerates liver regeneration in a partial hepatectomy rat model.

Hepatocyte growth factor (HGF) is central to liver regeneration. The Internalin B (InlB) protein is a virulence factor produced by the pathogenic bacterium Listeria monocytogenes. InlB is known to mimic HGF activity by interacting with the HGF receptor (HGFR) and activating HGFR-controlled signaling pathways. We expressed and purified the HGFR-binding InlB domain, InlB321/15, cloned from the fully virulent clinical L. monocytogenes strain. HGFR and Erk1/2 phosphorylation was determined using Western blotting. The capacity of InlB321/15 to bind HGFR was measured using microscale thermophoresis. Liver regeneration was studied in a model of 70% partial hepatectomy (70%PHx) in male Wistar rats. The nuclear grade parameters were quantified using manual (percentage of binuclear hepatocytes), automated (nuclear diameters), or combined (Ki67 proliferation index) scoring methods. Purified InlB321/15 stimulated HGFR and Erk1/2 phosphorylation and accelerated the proliferation of HepG2 cells. InlB321/15 bound HGFR with Kd = 7.4 ± 1.3 nM. InlB321/15 injected intravenously on the second, fourth, and sixth days after surgery recovered the liver mass and improved the nuclear grade parameters. Seven days post 70% PHx, the liver weight indexes were 2.9 and 2.0%, the hepatocyte proliferation indexes were 19.8 and 0.6%, and the percentages of binucleated hepatocytes were 6.7 and 4.0%, in the InlB321/15-treated and control animals, respectively. Obtained data demonstrated that InlB321/15 improved hepatocyte proliferation and stimulated liver regeneration in animals with 70% hepatectomy.