Comparison of Organoids from Menstrual Fluid and Hormone-Treated Endometrium: Novel Tools for Gynecological Research

Endometrial organoids (EMO) are an important tool for gynecological research but have been limited by generation from (1) invasively acquired tissues and thus advanced disease states and (2) from women who are not taking hormones, thus excluding 50% of the female reproductive-aged population. We sought to overcome these limitations by generating organoids from (1) menstrual fluid (MF; MFO) using a method that enables the concurrent isolation of menstrual fluid supernatant, stromal cells, and leukocytes and (2) from biopsies and hysterectomy samples from women taking hormonal medication (EMO-H). MF was collected in a menstrual cup for 4–6 h on day 2 of menstruation. Biopsies and hysterectomies were obtained during laparoscopic surgery. Organoids were generated from all sample types, with MFO and EMO-H showing similar cell proliferation rates, proportion and localization of the endometrial basalis epithelial marker, Stage Specific Embryonic Antigen-1 (SSEA-1), and gene expression profiles. Organoids from different disease states showed the moderate clustering of epithelial secretory and androgen receptor signaling genes. Thus, MFO and EMO-H are novel organoids that share similar features to EMO but with the advantage of (1) MFO being obtained non-invasively and (2) EMO-H being obtained from 50% of the women who are not currently being studied through standard methods. Thus, MFO and EMO-H are likely to prove to be invaluable tools for gynecological research, enabling the population-wide assessment of endometrial health and personalized medicine.

THE PRINCIPLE OF COMBINED PREOPERATIVE DIAGNOSIS OF THYROID TUMORS

The aim of the research is to increase the effectiveness of preoperative diagnosis of patients with thyroid tumors and to assess the use of cancer-embryonic antigen and immunocytochemical research. Materials and methods: Patients were interviewed about their complaints and lifestyle; performed ultrasound with fine-needle aspiration, determination of the level of cancer-embryonic antigen (CEA), cytological and immunocytochemical researches. Results: The Benign process in the thyroid gland is low serum REA (less than 0.95 ng / ml), poor expression of thyroglobulin (77.8%), negative reaction with TTF-1 (100%) and cytokeratin-19 (55.6%). Differential-prognostic markers of thyroid neoplasms with risk of malignancy include increased serum REA (0.95 ng / ml and above), the presence of a moderate reaction with antibodies to thyroglobulin (80.0%), a positive reaction — to TTF-1 (100.0%) and E-cadherin (90.0%), with moderate or strong expression of cytokeratin-19 (90.0%). Statistically significant markers of malignant thyroid disease were determined: the presence of harmful factors at work (45.5%), smoking (27.3%), elevated serum REA (0.95 ng / ml and above), the presence of strong cytoplasmic expression of thyroglobulin (63.6%), moderate or strong expression of TTF-1 (90.9%) and cytokeratin-19 (81.8%). Conclusions: The most appropriate and practically significant for preoperative diagnosis of thyroid tumors is a set of several diagnostic methods, which are carried out in one hospital – ultrasound with fine-needle aspiration, cytomorphological, and immunocytochemical and REA levels in a primary screening.

Near-infrared photoactiveYb-MOF functionalized with large conjugate ionic liquid: Synthesis and application for photoelectrochemical immunosensing carcinoma embryonic antigen

Near-infrared photoactive Yb-MOF functionalized with large conjugate ionic liquid: Synthesis and application for photoelectrochemical immunosensing carcinoma embryonic antigen Huiyue Lia, Ying Lia, Xue Zhanga, Pan Liua, Meng Hea, Chunya Lia,...

ROR1 sustains multivesicular endosomes by interacting with HRS and STAM1

The receptor tyrosine kinase-like orphan receptor 1 (ROR1) regulates caveolae formation and caveolae-dependent endocytosis by interacting with caveolae components, which in turn sustains pro-survival signaling toward AKT from multiple RTKs, including EGFR, and MET. We report here a novel function of ROR1 as a scaffold for HRS and STAM1, two essential components of ESCRT-0. The present results show that ROR1 facilitates interactions of HRS and STAM1, thereby preventing the lysosomal degradation of HRS. Furthermore, interaction of ROR1 with STAM1 was found to be required to sustain binding of ROR1 to HRS as well as HRS subcellular localization. Additionally, ROR1 localized in both the limiting membrane and intraluminal vesicles (ILVs) of Rab5-induced multivesicular endosomes (MVEs) containing HRS, CD63, and EEA1 was found to regulate the formation of Rab5-induced MVEs by an association with the GTP-bound form of Rab5 in cancer cells. Notably, ROR1 depletion inhibits CD63-positive MVEs formation and reduces exosomes release. Our findings provide the first evidence that the onco-embryonic antigen receptor ROR1 regulates exosome biogenesis via MVE formation in cancer cells.