Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective To investigate the effects of anaesthetic concentration of sevoflurane on TM3 mouse leydig cell viability.Methods TM3 mouse leydig cells were randomly divided into 3 groups ( n =24 dishes each):control group (group C),2％ and 5％ sevoflurane groups (groups SEV1 and SEV2 ).The cells were collected after being exposed to sevoflurane or 95 ％ room air + 5 ％ CO2 for 2,4 or 6 h (T1-3) for microscopic examination with optical binocular inverted microscope.The number of live cells was counted by using cell counting kit8.Gene chips were used to indentify differentially expressed genes between group C and group SEV2 after being exposed to air and 5 ％ sevoflurane for 6 h respectively.Results The leydig cell viability was significantly decreased at T3 in group SEV2 as compared with groups C and SEV1.Morphological changes were found only in group SEV2.A total of 45 genes were identified to be differentially expressed in group SEV2 as compared with group C.The level of expression of prostaglandin-endoperoxidase synthase 2 gene (Ptgs2),chemokine (C-C motif) ligand 2(CCL2) gene and dual specificity phosphatase1 (Dusp1) gene increased by at least 4 times in group SEV2.Conclusion Sevoflurane can inhibit the cell viability of TM3 mouse leydig cell in concentration dependent manner through abnormal expression of Ptgs2,CCL2 and Dusp1 genes.

Objective To investigate the effects of inhalation anesthetics on human sperm motility and capacitation in vitro. Methods Sperm samples were obtained from normal adults and prepared with discontinuous percoll gradient centrifugation technique. The samples were incubated for 5 h in an airtight glass container filledwith 5% CO2-95% air at 37 ℃ with or without sevoflurane (SEV 2%, 4% ) or isoflurane (ISO 1.1%, 2.2% ).Then human sperm motility was examined in vitro at 37℃ and analyzed by the computer-assisted sperm analysis (CASA), including sperm motility (a + b)%, curvilinear velocity (VCL), straight line velocity (VSL), averagepath velocity (VAP) and amplitude of lateral head displacement (ALH). The capacitation effect was assessed by using the chlortetracycline (CTC) staining and phase-contract microscopy. Results 2% and 4% SEV significantly reduced (a + b)% , VCL, VSL and VAP in a dose-dependent manner, while only 4% SEV significantly decreased ALH and the capacitation ability of the sperm compared with control group. 2.2% ISO significantly decreased ( a + b)%, VCL, VSL and VAP compared with control and 1.1% ISO group. The capacitation ability of the sperm was significantly decreased by 1.1% and 2.2% ISO as compared with control group. Conclusion Sevoflurane and isoflurane have significant inhibitory effects on human sperm motility and capacitation in a dose-dependent manner. Sevoflurane has stronger inhibitory effect than isoflurane.