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Background Brain tumors, whether primary or secondary, have limited information about proteomic changes despite advances in the understanding of the driver gene mutations and heterogeneity within tumor cells. In this study, we for the first time systematically analyzed the proteome of tumor tissues from patients with brain metastases (BrMs) and gliomas. Methods We assembled the most common primary tumors as follows: gliomas from WHO grade II to IV with or without IDH1 mutations; and BrMs with a wide range, including lung cancer (L.C), breast cancer (B.C), ovarian cancer (O.C), and colorectal cancer (C.C). A total of 29 tissue samples were analyzed by label free quantitative mass spectrometry-based proteomics. Results In total, 8,370 protein groups were identified, and approximately 4,000 quantified protein groups were adopted for further analysis. Proteomic analysis of metastatic tumors reveals conserved features across multiple cancers. While proteomic heterogeneities were found for discriminating low- and high-grade of gliomas, as well as IDH1 mutant and wild-type gliomas. And distinct pathway-level differences among these two types of brain malignancies were revealed. The characteristic pathways of BrMs focused on proliferation and immunomodulation after colonizing the brain, whereas invasion processes were notably activated in gliomas. Conclusion We elucidated an extensive proteomic landscape of BrMs and gliomas, providing information for the development of potential therapeutic and diagnostic strategies for type-specific brain tumors.

Introduction Placental dysfunction characterized by vascular endothelial inflammation is one of the most notable responses to fetal cardiac bypass. Regulator of calcineurin 1 (RCAN1) is an important regulator of inflammatory responses. MicroRNAs (miRNAs) are essential post-transcriptional modulators of gene expression, and miRNA-34a (miR-34a) was showed to activate vascular endothelial inflammation. We hypothesized that miR-34a may be a key regulator of placental dysfunction after fetal cardiac bypass. Methods We evaluated miRNA expression in goat placentas via small RNA sequencing, quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization. Expression of miRNA target genes was determined via bioinformatics analyses and dual luciferase reporter assays. Furthermore, human umbilical vein endothelial cells (HUVECs) were transfected with miR-34a or a control sequence. The RCAN1, nuclear factor of activated T-cells (NFATC1) and nuclear factor kappa-B (NF-κB) levels in HUVECs and placentas were evaluated via Western blot and qRT-PCR. Results We demonstrated that miR-34a was highly enriched in goat placenta after cardiopulmonary bypass. Moreover, RCAN1 was identified as a novel direct target of miR-34a. Transfection of miR-34a led to decreased RCAN1 expression and increased NFATC1 and NF-κB expression in HUVECs. Conversely, inhibition of miR-34a rescued RCAN1 expression and reduced NFATC1 and NF-κB expression in HUVECs. Conclusions We demonstrated a remarkable role of miR-34a as a regulator of NFATC1-associated placental inflammation through direct targeting of RCAN1. MiR-34a could serve as a novel therapeutic target for limiting the progression of placental inflammation after fetal cardiac bypass.

Objective Increasing evidence shows that some cardiac defects may benefit from fetal interventions, including fetal cardiac surgery. We attempted to develop an in vivo animal model of fetal cardiopulmonary bypass with cardioplegic arrest. Methods Operations were performed on 14 pregnant goats. The extracorporeal circulation circuit consisted of a centrifugal pump, silicone tubings with an inner diameter of 6 mm, a roller pump, and a reservoir. The placenta was the sole oxygenator. Cardiopulmonary bypass was maintained at a mean flow rate of 344 ± 68 mL/kg/min, including 30 minutes of cardiac arrest and 15 minutes of reperfusion. Mean arterial blood pressure and heart rate were monitored. Arterial blood samples were analyzed. The pulse index and resistance index of the fetal umbilical artery were monitored. Results Experiments were completed in 11 cases (79%), with the fetuses weighing 0.65 to 1.8 kg. Fetal mean arterial blood pressure and heart rate remained stable throughout the experiments. A decrease in partial pressure of oxygen with concomitant increase in carbon dioxide partial pressure was noted, but trends were relatively stable. Metabolic acidosis was recognized during and after cardiac bypass. The pulse index and resistance index of the umbilical artery increased significantly after 2 hours off bypass. Conclusions We confirmed the technical feasibility of establishing an in vivo model of fetal cardiac bypass with cardioplegic arrest. This fetal goat model provides reproducible data and is suitable to study clinically relevant problems related to fetal cardiopulmonary bypass, myocardial protection, and hemodynamics.