RESUMEN
Background: Preclinical and clinical evidence suggests that hyperbaric oxygen therapy (HBOT) may benefit newborns. The effectiveness of HBOT for neonatal hypoxic-ischemic encephalopathy (HIE) remains controversial. We conducted a meta-analysis to evaluate the efficacy and prognosis of HBOT in neonates with HIE. Methods: A systematic search of eight databases was performed for available articles published between January 1, 2015, and September 30, 2020, to identify randomized controlled clinical trials (RCTs) on HBOT for neonatal HIE. Methodological quality assessment was performed by applying the simple procedure detailed by the Cochrane collaboration. Afterward, quality assessment and data analysis were performed using Revman 5.3 software. STATA 15 software was used to detect publication bias as well as for sensitivity analysis. Results: A total of 46 clinical RCTs were selected for the study and included 4,199 patients with neonatal HIE. The results indicated that HBOT significantly improved the total efficiency (TEF) of treatment for neonatal HIE patients [odds ratio (OR) = 4.61, 95% confidence interval (CI) (3.70, 5.75), P < 0.00001] and reduced the risk of sequelae (OR = 0.23, 95% CI (0.16, 0.33), P < 0.00001) and the neonatal behavioral neurological assessment (NBNA) scores [mean difference (MD) = 4.51, 95%CI (3.83,5.19, P < 0.00001)]. Conclusion: In light of the effectiveness of HBOT neonatal HIE, this meta-analysis suggested that HBOT can be a potential therapy for the treatment of neonatal HIE. Due to the heterogeneity of studies protocol and patient selection being only from China, more research is needed before this therapy can be widely implemented in the clinic. Protocol Registration: PROSPERO (ID: CRD42020210639). Available online at: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020210639.
RESUMEN
The intratumoral androgen synthesis is one of the mechanisms by which androgen receptor (AR) is aberrantly re-activated in castration-resistant prostate cancer (CRPC) after androgen ablation. However, pathways controlling steroidogenic enzyme expression and de novo androgen synthesis in prostate cancer (PCa) cells are largely unknown. In this study, we explored the potential roles of DAB2IP in testosterone synthesis and CRPC tumor growth. Indeed, DAB2IP loss could maintain AR transcriptional activity, PSA re-expression and tumor growth under castrated condition in vitro and in vivo, and reprogram the expression profiles of steroidogenic enzymes, including AKR1C3. Mechanistically, DAB2IP could dramatically inhibit the AKR1C3 promoter activity and the conversion from androgen precursors (i.e., DHEA) to testosterone through PI3K/AKT/mTOR/ETS1 signaling. Consistently, there was a high co-expression of ETS1 and AKR1C3 in PCa tissues and xenografts, and their expression in prostate tissues could also restore AR nuclear staining in castrated DAB2IP-/- mice after DHEA supplement. Together, this study reveals a novel regulation of intratumoral de novo androgen synthesis in CRPC, and provides the DAB2IP/ETS1/AKR1C3 signaling as a potential therapeutic target.