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 evaluate the reliability and validity of the Chinese version of the Personal and Social Performance scale (PSP-CHN) in patients with schizophrenia.Methods:Totally 165 out-patients and in-patients meeting the DSM-IV-TR criteria for schizophrenia were entered in the study.Ten of subjects was included the intra-rater reliability training.The Global Assessment of Functioning Scale (GAF) was regarded as the' gold standard' to investigate the validity of PSP-CHN,and the Positive and Negative Rating Scale was used to assess the severity of disease to explore the correlative validity,in the other 155 subjects.Five to seven days after the first PSP-CHN interview,the second PSP-CHN was evaluated by another investigator to assess the test-retest reliability among 66 subjects.Twenty-seven subjects with the score of Positive and Negative Syndrome Scale (PANSS) more than 60 were followed up for 8 weeks of standardized pharmacotherapy.By the end of 8 week of treatment,the PANSS and PSP-CHN were assessed again to explore the sensitivity of PSP-CHN.Results:The internal consistency (Cronbach α=0.84) and the inter-rater reliability (κ value=0.56,ICC=0.94 for PSP-CHN total score) were good.The test-retest reliability was high [intraclass correlation coefficient (ICC) of 0.95].The scale showed good construct validity with statistically significant correlations with the Global Assessment of Functioning Scale (GAF) (ICC of 0.95).The PSP-CHN score had a good negative correlation with the PANSS total score(r=-0.79,-0.57,-0.63 and -0.71,respectively,P<0.01).After 8 week treatment,PSP-CHN total score was increased with the improvement of PANSS,and the responder showed higher increasing of PSP-CHN total score (21.2) than those partial responder(10.2),significantly.Conclusion:The Chinese version of the PSP-CHN is a convenient and valid instrument to assess the personal and social functions of stabilized and acute patients with schizophrenia.

OBJECTIVE: To study synergistic effect of Vitamin C (VitC) combined with arsenic trioxide (As2 O3)-on human laryngocarcinoma Hep-2 cell line apoptosis. METHOD: Human laryngocarcinoma cell line Hep-2 was cultured in vitro, and incubated with As2 O3 or jointly with VitC. The inhibition ability of Hep-2 cells was determined by methyl thiazolyl tetrazolium (MTT) assay, while the apoptosis was mensurated by the flow cytometry with Annexin-V/PI. RESULT: Compared with the use of As2 O3 separately, the combination of As2 O3 and VitC could increase the inhibition ability and the apoptosis rate of Hep-2 cells markedly (P < 0.05). CONCLUSION Combination of As2 O3 with VitC could markedly increase arsenic trioxide (As2 O3)-induced apoptosis of Hep-2 cells.
Apoptosis ; drug effects ; Arsenic Trioxide ; Arsenicals ; pharmacology ; Ascorbic Acid ; pharmacology ; Cell Line, Tumor ; Drug Synergism ; Humans ; Oxides ; pharmacology