The PAPSS1 gene is a modulator of response to cisplatin by regulating estrogen receptor alpha signaling activity in ovarian cancer cells.

BACKGROUND: Cancer cells may develop resistance to cisplatin by various mechanisms. Yet, the exact mechanism of cisplatin in ovarian cancer remains unclear. Recent studies have shown that 3'-phospoadenosine 5'-phosphosulfate synthase 1 (PAPSS1) inhibition combined with low-dose cisplatin increases DNA damage. The aim of this study was to determine the value of targeting PAPSS1 as a cisplatin modulator in epithelial ovarian cancer (EOC). RESULTS: Increased expression of PAPSS1 was observed in both EOC cells and tissues. Also, its higher nuclear expression was distinctly associated with FIGO (The International Federation of Gynecology and Obstetrics) stage, histological subtype, metastasis, and recurrence. Down-regulation of the PAPSS1 gene increased the cisplatin sensitivity of EOC in vitro and in vivo. Expression of PAPSS1 was negatively correlated with estrogen receptor α (ERα) in EOC. Also, low nuclear PAPSS1 and high nuclear ERα expression in EOC were associated with longer overall survival and progression-free survival in all ovarian cancer and ovarian cancer patients who received platinum-based chemotherapy. PAPSS1 silencing increased the activity of ERα-signaling in EOC cells, thus sensitizing tumors to cisplatin. CONCLUSIONS: These findings characterize a novel interplay between PAPSS1-mediated sulfation and ERα-signaling in EOC cisplatin resistance. PAPSS1 may be exploited as a cisplatin-sensitizing therapeutic target.

Effective Material Basis and Mechanism Analysis of Compound Banmao Capsule against Tumors Using Integrative Network Pharmacology and Molecular Docking.

PURPOSE: Compound banmao capsule (CBC), a well-known traditional Chinese medical material, is known to inhibit various tumors. However, its material basis and pharmacological mechanisms remain to be elucidated. This study aimed to investigate the effective material basis and mechanisms of action of CBC against tumors. METHODS: Active compounds of CBC were identified using public database and reports to build a network. The corresponding targets of active compounds were retrieved from online databases, and the antitumor targets were identified by GeneCards database. The antitumor hub targets were generated via protein-protein interaction analysis using String, and key compounds and targets from the integrative network were detected by molecular docking and ADMET. Top targets in hepatocellular carcinoma were confirmed by quantitative real-time PCR (qPCR). Finally, the multivariate biological network was built to identify the integrating mechanisms of action of CBC against tumor cells. RESULTS: A total of 128 compounds and 436 targets of CBC were identified successfully. Based on the generated multivariate biological network analysis, 25 key compounds, nine hub targets, and two pathways were further explored. Effective material bases of cantharidin, baicalein, scutellarin, sesamin, and quercetin were verified by integrative network analysis. PTGS2, ESR1, and TP53 were identified as hub targets via multivariate biological network analysis and confirmed using qPCR. Furthermore, VEGF and estrogen signaling pathways seem to play a role in the antitumor activity of CBC. Thus, breast cancer may be a potential clinical indication of CBC. CONCLUSION: This study successfully identified the material basis of CBC and its synergistic mechanisms of action against tumor cells.

[Risk factors for hypoglycemia in preterm infants with a gestational age of ≤32 weeks].

OBJECTIVE: To investigate the risk factors for hypoglycemia after birth in preterm infants with a gestational age of ≤32 weeks. METHODS: A retrospective analysis was performed for 86 neonates with hypoglycemia and a gestational age of ≤32 weeks who were admitted to the neonatal intensive care unit from January 2017 to June 2020 (hypoglycemia group). A total of 172 preterm infants with normal blood glucose who were hospitalized during the same period were randomly enrolled as the control group. Univariate analysis and multivariate logistic regression analysis were used to screen out the risk factors for hypoglycemia in preterm infants. RESULTS: There were 515 preterm infants during the study, among whom 86 (16.7%) had hypoglycemia. Compared with the control group, the hypoglycemia group had significantly higher percentages of small for gestational age (SGA), cesarean section, maternal hypertension, and antenatal steroid administration (P<0.05), but significantly lower birth weight and rate of intravenous glucose use before blood glucose test (P<0.05). SGA (OR=4.311, 95%CI: 1.285-14.462, P<0.05), maternal hypertension (OR=2.469, 95%CI: 1.310-4.652, P<0.05), and antenatal steroid administration (OR=6.337, 95%CI: 1.430-28.095, P<0.05) were risk factors for hypoglycemia in preterm infants, while intravenous glucose use (OR=0.318, 95%CI: 0.171-0.591, P<0.05) was a protective factor against hypoglycemia in preterm infants. CONCLUSIONS: SGA, maternal hypertension, and antenatal steroid administration may increase the risk of early hypoglycemia in preterm infants with a gestational age of ≤32 weeks, and intravenous glucose use is recommended as soon as possible after birth for preterm infants with a gestational age of ≤32 weeks to reduce the incidence rate of hypoglycemia.