ANP32B-mediated repression of p53 contributes to maintenance of normal and CML stem cells.

Proper regulation of p53 signaling is critical for the maintenance of hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs). The hematopoietic cell-specific mechanisms regulating p53 activity remain largely unknown. Here, we demonstrate that conditional deletion of acidic leucine-rich nuclear phosphoprotein 32B (ANP32B) in hematopoietic cells impairs repopulation capacity and postinjury regeneration of HSCs. Mechanistically, ANP32B forms a repressive complex with p53 and thus inhibits the transcriptional activity of p53 in hematopoietic cells, and p53 deletion rescues the functional defect in Anp32b-deficient HSCs. Of great interest, ANP32B is highly expressed in leukemic cells from patients with chronic myelogenous leukemia (CML). Anp32b deletion enhances p53 transcriptional activity to impair LSC function in a murine CML model and exhibits synergistic therapeutic effects with tyrosine kinase inhibitors in inhibiting CML propagation. In summary, our findings provide a novel strategy to enhance p53 activity in LSCs by inhibiting ANP32B and identify ANP32B as a potential therapeutic target in treating CML.

An investigation of the time trends, risk factors, role of ultrasonic preoperative diagnosis of 79 ovarian pregnancy.

BACKGROUND: Ovarian pregnancy (OP) is a rare form of ectopic pregnancy and is still a medical challenge. Therefore, more studies about the time trends, risk factors and diagnostic measurements are needed for the efficient treatment of OP. METHODS: The datum of OP patients who were treated at the Second Hospital of Hebei Medical University from 2003 to 2018 was collected and a retrospective cohort study was preformed between OP and tubal pregnancy. RESULTS: 79 of all 6943 ectopic pregnancy (1.14%) were OP. The prevalence of OP following assisted reproductive technology showed an increasing trend over time, from 8.33% to 15.22%. Previous abdominal surgery was one of the risk factors of OP (OR 0.41, 95% CI 0.18-0.95, p = 0.04). Merely 2 (2.53%) patients were sonographically diagnosed as OP accorded with their discharge diagnosis. However, 56 (80.0%) accumulation of blood in the pelvis formed echo free areas could be clearly found by ultrasonography. A significant difference was found in serum ß-hCG level among OP patients and tubal pregnancy patients (2762.73 ± 1915.24 mmol/L vs 1034.20 ± 915.32 mmol/L, p < 0.001). CONCLUSIONS: The prevalence of OP following assisted reproductive technology is on the rise. History of abdominal surgery may be a high risk factor for OP patients who have the tendency of high ß-hCG levels. The ultrasonic preoperative diagnosis is conductive to the early diagnosis of OP though the diagnosis accuracy is low.

[Effect of Asparaginase on Diffuse Large B-Cell Lymphoma Cell Apoptosis and Its Related Mechanism].

OBJECTIVE: To investigate the effects and its potential mechanism of asparaginase on proliferation, cell cycle and apoptosis of diffuse large B-cell lymphoma (DLBCL) cell lines. METHODS: CCK-8 assay was used to detect the effect of asparaginase on proliferation of DLBCL cell lines. Flow cytometry was used to analyze cell cycle and apoptosis. Western blot was used to analyze apoptosis and its potential mechanism. RESULTS: Asparaginase obviously inhibited the proliferation of multiple DLBCL cell lines and caused G0/G1 cell arrest. Furtherly, asparaginase inhibited the expression of HIF-1α which related to poor prognosis of patients with DLBCL, up-regulated the expression of DR4 and caspase 8, reduce the expression of c-FLIP. Meanwhile, asparaginase induced the expression of pro-apoptotic protein BAX and inhibited the expression of anti-apoptotic protein MCL-1. CONCLUSION: Asparaginase can inhibit the proliferation of DLBCL cell lines, cause the arrest of cells in G0/G1 and induce apoptosis via the endogenous and exogenous apoptotic pathways.

FBXO22 mediates polyubiquitination and inactivation of LKB1 to promote lung cancer cell growth.

Liver kinase B1 (LKB1) regulates both cell growth and energy metabolism. Inactivated mutations of LKB1, observed in 20-30% of nonsmall cell lung cancers (NSCLC), contribute significantly to lung cancer malignancy progression. However, the upstream signalings regulating LKB1 activity remain incompletely understood. Here, we present evidence that FBXO22 interacts with and promotes polyubiquitination of LKB1. More intriguingly, FBXO22 mediates Lys-63-linked LKB1 polyubiquitination and inhibits kinase activity of LKB1. Furthermore, over-expression of FBXO22 promotes NSCLC cell growth through inhibiting LKB1-AMPK-mTOR signaling in vitro and in vivo. Clinically, FBXO22 is highly expressed in human lung adenocarcinoma and high FBXO22 expression predicts significant poor prognosis. Our study provides new insights into the upstream regulation of LKB1 activation and identifies FBXO22 as a potential therapeutic target for lung cancer treatment.

[Clinical features and prognosis of preterm infants with varying degrees of bronchopulmonary dysplasia].

OBJECTIVE: To study the clinical features and prognosis of preterm infants with varying degrees of bronchopulmonary dysplasia (BPD). METHODS: The clinical data of 144 preterm infants with a gestational age of <32 weeks who were admitted to the neonatal intensive care unit from March 2014 to March 2016 and were diagnosed with BPD were collected. According to the severity of BPD, these preterm infants were divided into mild group with 81 infants and moderate/severe group with 63 infants. The two groups were compared in terms of perinatal risk factors, treatment, comorbidities, complications, and prognosis of the respiratory system. RESULTS: Compared with the mild BPD group, the moderate/severe BPD group had a significantly higher gestational age and rate of small-for-gestational-age (SGA) infants (P<0.05), as well as a significantly higher rate of severe preeclampsia and a significantly lower rate of threatened preterm labor (P<0.05). Compared with the mild BPD group, the moderate/severe BPD group had a significantly higher percentage of infants who needed mechanical ventilation at 2 weeks after birth, longer duration of mechanical ventilation, total time of oxygen therapy, and length of hospital stay, and higher incidence rates of pneumonia and cholestasis (P<0.05), as well as a significantly lower application rate of caffeine citrate (P<0.05). The multivariate logistic regression analysis showed that SGA birth (OR=5.974, P<0.05), pneumonia (OR=2.590, P<0.05), and mechanical ventilation required at 2 weeks after birth (OR=4.632, P<0.05) were risk factors for increased severity of BPD. The pulmonary function test performed at the corrected gestational age of 40 weeks showed that compared with the mild BPD group, the moderate/severe BPD group had significantly lower ratio of time to peak tidal expiratory flow to total expiratory time, ratio of volume to peak tidal expiratory flow to total expiratory volume, and tidal expiratory flow at 25% remaining expiration (P<0.05). The infants were followed up to the corrected gestational age of 1 year, and the moderate/severe BPD group had significantly higher incidence rates of recurrent hospital admission for pneumonia and recurrent wheezing (P<0.05). CONCLUSIONS: SGA birth, pneumonia, and prolonged mechanical ventilation are associated with increased severity of BPD. Infants with moderate or severe BPD have poor pulmonary function and may experience recurrent infection and wheezing.