Recent Developments in Biomaterial-Based Hydrogel as the Delivery System for Repairing Endometrial Injury.

Endometrial injury caused by intrauterine surgery often leads to pathophysiological changes in the intrauterine environment, resulting in infertility in women of childbearing age. However, clinical treatment strategies, especially for moderate to severe injuries, often fail to provide satisfactory therapeutic effects and pregnancy outcomes. With the development of reproductive medicine and materials engineering, researchers have developed bioactive hydrogel materials, which can be used as a physical anti-adhesion barrier alone or as functional delivery systems for intrauterine injury treatment by loading stem cells or various active substances. Studies have demonstrated that the biomaterial-based hydrogel delivery system can provide sufficient mechanical support and improve the intrauterine microenvironment, enhance the delivery efficiency of therapeutic agents, prolong intrauterine retention time, and perform efficiently targeted repair compared with ordinary drug therapy or stem cell therapy. It shows the promising application prospects of the hydrogel delivery system in reproductive medicine. Herein, we review the recent advances in endometrial repair methods, focusing on the current application status of biomaterial-based hydrogel delivery systems in intrauterine injury repair, including preparation principles, therapeutic efficacy, repair mechanisms, and current limitations and development perspectives.

Knockdown of LMTK3 in the Endometrioid Adenocarcinoma Cell Line Ishikawa: Inhibition of Growth and Estrogen Receptor α.

OBJECTIVE: The curative effect of high-efficiency progesterone and other therapeutic drugs for endometrioid adenocarcinoma patients with preservation of reproductive capacity has not been satisfactory so far. Novel therapeutic drugs need to be explored. METHODS: We investigated the cytoplastic and nuclear expression levels of LMTK3 between endometrioid adenocarcinoma tissues and adjacent endometrial tissues by immunohistochemistry. We detected the effects of LMTK3 on cell viability of Ishikawa cells by CCK-8. We detected the effects of LMTK3 on cell cycle and apoptosis of Ishikawa cells by flow cytometry. We also detected the effects of LMTK3 knockdown on mRNA and protein levels of ERα by qRT-PCR and western blotting, respectively. We also used the cBioPortal online database to analyze the coexpression of LMTK3 and ESR1 in 1647 UCEC samples. RESULTS: We used TMAs to identify that LMTK3 was mainly detected in the cytoplasm of endometrioid tissues, and cytoplasmic LMTK3 expression in endometrioid tissues was higher than that in adjacent endometrial tissues (P < 0.05). LMTK3 knockdown decreased the proliferation of Ishikawa cells through decreasing cell viability (P < 0.01), increasing G1 (P < 0.001) arrest, and promoting apoptosis (P < 0.01). There was a positive correlation between the mRNA expression levels of LMTK3 and ESR1 (Spearman: P=2.011e-5, R=0.13; Pearson: P=7.18e-8, R=0.17). Knockdown of LMTK3 also reduced the mRNA (P < 0.001) and protein (P < 0.001) levels of ERα. CONCLUSIONS: Inhibitors of LMTK3 may be a possible future treatment for ERα and LMTK3 highly expressed endometrioid adenocarcinoma following appropriate studies.

RSF1 in cancer: interactions and functions.

RSF1, remodelling and spacing factor 1, is an important interphase centromere protein and is overexpressed in many types of cancers and correlated with poor overall survival. RSF1 has functions mainly in maintaining chromosome stability, facilitating DNA repair, maintaining the protein homeostasis of RSF1 and suppressing the transcription of some oncogenes when RSF1 protein is expressed at an optimal level; however, RSF1 overexpression facilitates drug resistance and cell cycle checkpoint inhibition to prompt cancer proliferation and survival. The RSF1 expression level and gene background are crucial for RSF1 functions, which may explain why RSF1 has different functions in different cancer types. This review summarizes the functional domains of RSF1, the overexpression status of RSF1 and SNF2H in cancer based on the TCGA and GTEX databases, the cancer-related functions of RSF1 in interacting with H2Aub, HDAC1, CENP-A, PLK1, ATM, CENP-S, SNF2H, HBX, BubR1, cyclin E1, CBP and NF-κB and the potential clinical value of RSF1, which will lay a theoretical foundation for the structural biology study of RSF1 and application of RSF1 inhibitors, truncated RSF1 proteins and SNF2H inhibitors in the treatment of RSF1-overexpressing tumours.

Treatment of upper urinary tract urothelial carcinoma.

Upper urinary tract urothelial carcinoma (UUTUC) is relatively rare, occurring in only 5% of all urothelial cancers. It has not been as extensively studied and reviewed as carcinoma of the bladder. UUTUC has a propensity for multifocality, local recurrence, and development of metastases, which argues for an aggressive treatment approach. Open radical nephroureterectomy (ORNU) with removal of an ipsilateral bladder cuff still remains the gold standard treatment for patients with UUTUC and a normal contralateral kidney, which, however, is being challenged by minimally invasive approaches, such as endoscopic and laparoscopic approaches. They are rapidly evolving as reasonable alternatives of care depending on grade and stage of disease. Adjuvant therapy seems to be safe, although its efficacy is debatable. Immunotherapy appears to be most effective in patients with upper-tract carcinoma in situ. Chemotherapy and radiotherapy also show some improvement in recurrence rates, but there have been no randomized, prospective trials. Gene and molecular-targeted therapy is expected. Several controversies remain in our management, including a selection of endoscopic versus laparoscopic approaches, management strategies on the distal ureter, the role of lymphadenectomy, and the value of immunotherapy, chemotherapy, radiotherapy and genetics and molecular markers in UUTUC. Aims of this paper are to critically review the treatment of UUTUC.