SP6 controls human cytotrophoblast fate decisions and trophoblast stem cell establishment by targeting MSX2 regulatory elements.

The commitment and differentiation of human placental progenitor cytotrophoblast (CT) cells are crucial for a successful pregnancy, but the underlying mechanism remains poorly understood. Here, we identified the transcription factor (TF), specificity protein 6 (SP6), as a human species-specific trophoblast lineage TF expressed in human placental CT cells. Using pluripotent stem cells as a model, we demonstrated that SP6 controls CT generation and the establishment of trophoblast stem cells (TSCs) and identified msh homeobox 2 (MSX2) as the downstream effector in these events. Mechanistically, we showed that SP6 interacts with histone acetyltransferase P300 to alter the landscape of H3K27ac at targeted regulatory elements, thereby favoring transcriptional activation and facilitating CT cell fate decisions and TSC maintenance. Our results established SP6 as a regulator of the human trophoblast lineage and implied its role in placental development and the pathogenies of placental diseases.

Identification of G protein subunit alpha i2 as a promising therapeutic target of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a global health problem. Its incidence and mortality are increasing. Exploring novel therapeutic targets against HCC is important and urgent. We here explored the expression and potential function of Gαi2 (G protein subunit alpha i2) in HCC. The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) database shows that the number of Gαi2 transcripts in HCC tissues is significantly higher than that in the normal liver tissues. Moreover, Gαi2 overexpression in HCC correlates with poor prognosis of the patients. Gαi2 mRNA and protein expression are also elevated in local HCC tissues and different human HCC cells. In patient-derived primary HCC cells and immortalized HepG2 cells, Gαi2 silencing (by targeted shRNA) or knockout (KO, by the dCas9-sgRNA method) largely suppressed cell proliferation and motility, while inducing cell cycle arrest and caspase-apoptosis activation. Moreover, Gαi2 silencing or KO-induced reactive oxygen species (ROS) production and oxidative injury in primary and HepG2 HCC cells. Whereas different antioxidants ameliorated Gαi2-shRNA-induced anti-HCC cell activity. Using a lentiviral construct, Gαi2 overexpression further augmented proliferation and motility of primary and immortalized HCC cells. Further studies revealed that the binding between the transcription factor early growth response zinc finger transcription factor 1 (EGR1) and Gαi2 DNA promoter was significantly increased in HCC tissues and cells. In vivo, intratumoral injection of Gαi2 shRNA adeno-associated virus significantly hindered HCC xenograft growth in nude mice. Moreover, the growth of Gαi2-KO HCC xenografts in the nude mice was remarkably slow. Gαi2 depletion, oxidative injury, and apoptosis induction were detected in Gαi2-silenced or Gαi2-KO HCC xenografts. Together, overexpressed Gαi2 is required for HCC cell growth in vitro and in vivo, representing as a novel and promising diagnosis marker and therapeutic target of HCC.

In vivo microscopy of arterial distribution embolic particles in rabbit mesenteric artery.

PURPOSE: To study the arterial distribution of embosphere microsphere (EM) and polyvinyl alcohol (PVA) particles in rabbit mesenteric artery using in vivo microscopy.To study the arterial distribution of embosphere microsphere (EM) and polyvinyl alcohol (PVA) particles in rabbit mesenteric artery using in vivo microscopy. METHODS: Sixteen New Zealand rabbits were divided into four groups, namely large PVA (560-710 µm), small PVA (150-350 µm), large EM (500-700 µm), and small EM (100-300 µm). The mesenteric arteries of the experimental animals were embolized under fluoroscopic guidance and visualized using in vivo microscopy. The embolized vessel diameter and arterial distribution of embolic agents were compared. RESULTS: The diameters of occluded vessels in large PVA, small PVA, large EM, and small EM groups were 430.60 ± 67.30, 200.95 ± 70.54, 387.79 ± 92.51, and 143.81 ± 39.65 µm, respectively. PVA occluded significantly larger vessels than EM when the particle size was similar (P < 0.001). The proportion of EM at the bifurcation of the artery was significantly higher than that of PVA particles (large PVA < large EM, χ2 = 4.325, P < 0.038; small PVA < small EM, χ2 = 6.68, P < 0.01). CONCLUSION: Both PVA and EM could occlude vessels smaller than the particle size, and EM resulted in deeper penetration. The location of embolic particles in the artery is mainly related to the shape of particles.

Modified one-session endovascular treatment for deep venous thrombosis with high risk of pulmonary embolism: Short-term outcomes.

OBJECTIVES: To evaluate the safety and short-term outcomes of the modified one-session endovascular treatment with inferior vena cava filter placement and retrieval in one stage for the treatment of acute lower extremity deep vein thrombosis. METHOD: Twenty-three patients with unilateral acute lower extremity deep vein thrombosis underwent modified one-session endovascular treatments, which were performed in one stage. Inferior vena cava filter placement without detachment, thrombectomy, and inferior vena cava filter retrieval were performed in one stage. Angioplasty and stent implantation were performed for patients with iliac vein stenosis. Venography was performed to identify the clearance of the thrombus. Color Doppler ultrasound and/or venography were conducted during the follow-up. RESULTS: A total of 20/23 (87%) patients with thrombus removal rate >90% successfully underwent modified one-session endovascular treatment. inferior vena cava filters were detached in 3/23 (13%) patients achieving 50%-90% thrombus removal rate. Twenty-one iliac vein stents were implanted in 21/23 (91%) patients with iliac vein stenosis. After treatment, the differences in the circumferences of the affected limb and the healthy limb both significantly decreased. No procedure-related death, symptomatic pulmonary embolism, or major bleeding occurred. During the 12-25 months of follow-up, iliac vein stents and lower extremity veins maintained patent. CONCLUSIONS: The modified one-session endovascular treatment with one-stage inferior vena cava filter placement and retrieval might be safe for the treatment of acute lower extremity deep vein thrombosis, and the early clinical outcomes are satisfactory. Placing and retrieving an inferior vena cava filter in one session could safeguard the endovascular interventions as well as reduce the filter-related complications associated with long dwelling times.