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Liu Z.,Chongqing Medical University | Luo Q.,Chongqing Medical University | Guo C.,Chongqing Medical University | Guo C.,Ministry of Education Key Laboratory of Child Development and Disorders
Cancer Cell International | Year: 2015

Background: ATF2 mediated cytochrome c release is the formation of a channel with some unknown factors larger than that of the individual proteins. BHS-only proteins (BH3s), such as Bim, could induce BAX and VDAC, forming a new channel. According to this facts, we can speculated that there is possible signal relationship with BH3s and ATF2, which is associated with mitochondrial-based death programs. Methods: The growth inhibitory effects of mitochondrial ATF2 were tested in cancer cell lines B16F10, A549, EG7, and LL2. Apoptosis was measured by flow cytometry. The effects of ATF2 and levels of apoptosis regulatory proteins were measured by Western blotting. The interaction of proteins were evaluated by immunoprecipitation analysis. The in vivo antitumor activity of mitochondrial ATF2 were tested in xenograft B16F10 models. Results: Genotoxic stress enabled mitochondrial ATF2 accumulation, perturbing the HK1-VDAC1 complex, increasing mitochondrial permeability, and promoting apoptosis. ATF2 inhibition strongly reduced the conformational activation of Bim, suggesting that Bim acts downstream of ATF2. Although Bim downregulation had no effect on ATF2 activation, Bim knockdown abolished VDAC1 activation; the failure of VDAC1 activation in Bim-depleted cells could be reversed by the BH3-only protein mimic ABT-737. We also demonstrate that silencing of ATF2 in B16F10 cells increases both the incidence and prevalence of tumor xenografts in vivo, whereas stably mitochondrial ATF2 transfection inhibited B16F10 tumor xenografts growth. Conclusions: Altogether, these results show that ATF2 is a component of the apoptosis machinery that involves a hierarchical contribution of ATF2, Bim, and VDAC1. Our data offer new insight into the mechanism of mitochondrial ATF2 in mitochondrial apoptosis. © Liu et al.

Wang J.,Chongqing Medical University | Wang J.,Ministry of Education Key Laboratory of Child Development and Disorders | Wang J.,Key Laboratory of Pediatrics in Chongqing CSTC2009CA5002 | Huang Y.,Chongqing Medical University | And 4 more authors.
Tuberculosis | Year: 2011

In vitro and in animal studies have suggested an important role for the Mycobacterium tuberculosis PE-PGRS33 protein in the pathogenesis of TB. A significant level of PE-PGRS33 gene DNA polymorphism among clinical isolates from adult tuberculosis (TB) patients and its association with clinical and epidemiological phenotypes of the disease has been found. To better understand the role of PE-PGRS33 protein in the pathogenesis pediatric TB, we investigated DNA polymorphism of the PE-PGRS33 gene among 101 of pediatric TB patients' isolates and assessed the relationship between the PE-PGRS33 sequence variation and clinical characteristics of TB. Twelve different PE-PGRS33 sequence variations representing 12 different alleles were observed among the 101 M. tuberculosis clinical isolates investigated. Of these 101 isolates, 62(59.41%) had PE-PGRS33 alleles that would result in a change in the amino acid sequence of the PE-PGRS33 protein. The degree of DNA polymorphism within individual M. tuberculosis isolates from pediatric TB patients was remarkably lower than that previously found in M. tuberculosis isolates from adults TB patients. The frequency distribution of isolates having PE-PGRS33 gene sequence variations was similar between Beijing and non-Beijing families of the pathogen. Patients having TB meningitis and negative PPD skin test results appeared to be more likely to be infected by isolates having a mutant type of the PE-PGRS33 gene than patients who had no TB meningitis (OR 2.54, 95% CI [1.11-5.84]) and patients who had positive PPD-skin test results (OR 4.26, 95% CI [1.14-12.86]), respectively. This study provides new insight into the molecular pathogenesis of pediatric TB. © 2011 Elsevier Ltd. All rights reserved.

Gao W.,Chongqing Medical University | Gao W.,Ministry of Education Key Laboratory of Child Development and Disorders | Pan B.,Chongqing Medical University | Pan B.,Ministry of Education Key Laboratory of Child Development and Disorders | And 6 more authors.
Biochemical and Biophysical Research Communications | Year: 2015

Alcohol abuse during pregnancy may cause fetal cardiac developmental abnormalities. Our previous studies showed that alcohol could induce histone hyperacetylation and over-expression of cardiac transcription factors both in vivo and in vitro. The objective of the present study was to investigate the role of ERK1/2 signaling pathway in alcohol-induced histone hyperacetylation and up-regulation of cardiac transcription factors in H9c2 cells. The Cardiac cell line H9c2 was cultured with alcohol. U0126, a specific inhibitor of ERK1/2 pathway was employed to block the ERK1/2 signaling pathway. Western blotting analysis showed that alcohol significantly enhanced the levels of phosphorylated ERK1/2 and induced hyperacetylation of histone3, which were both effectively prevented with U0126. Real-time PCR showed that U0126 treatment significantly decreased alcohol-induced over-expression of GATA4 and MEF2c, and the basal expression level of GATA4, but did not affect MEF2c. ChIP assay showed that U0126 treatment significantly decreased alcohol-induced hyperacetylation of histone3 near the promoter regions of GATA4 and MEF2c. The basal acetylation level of histone3 near the promoter region of GATA4 was affected by U0126 as well, but not that near the promoter region of MEF2c. These data indicated that ERK1/2 signaling played an important role in mediating alcohol induced over-expression of GATA4 and MEF2c, which is possibly through the up-regulation of acetylation of histone3 near the gene promoters that affects the expression of GATA4 and MEF2c in H9c2 cells. ERK1/2 pathway might be a potential target for the intervention of alcohol induced congenital heart diseases. © 2015 Elsevier Inc.

Li S.,Chongqing Medical University | Li S.,Ministry of Education Key Laboratory of Child Development and Disorders | Guo P.,Chongqing Medical University | Guo P.,Key Laboratory of Pediatrics in Chongqing | And 6 more authors.
PLoS ONE | Year: 2016

Objective: This meta-analysis aimed to investigate the efficacy and safety of plastic wrap applied after birth and during NICU in preterm infants for prevention of heat loss in preterm infants. Study Methods: The Medline (1950 to August 2015), the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 7, 2015), CINAHL (1982 to August 2015) and the Embase (1974 to August 2015) databases were searched for randomized controlled trials (RCTs) or quasi- RCTs with main outcomes related to the core temperature (baseline temperature and/or post-stabilization temperature), hypothermia, mortality rate and hyperthermia. Result: The included studies were of low to moderate quality. Compared with unwrapped infants, plastic wrap was associated with a significantly higher baseline temperature and post-stabilization temperature both in infants < 28 weeks of gestation (mean difference [MD] = 0.62, 95% CI 0.38 to 0.85; MD = 0.41, 95% CI 0.33 to 0.50, respectively), and in infants between 28 to 34 weeks of gestation (MD = 0.54, 95% CI 0.21 to 0.87; MD = 0.64, 95% CI 0.45 to 0.82, respectively). Use of plastic wrap was associated with lower incidence of hypothermia (relative risk [RR] = 0.70, 95% CI 0.63 to 0.78). However, use of plastic wrap in preterm infants was not associated with decrease in mortality (RR: 0.88, 95% CI 0.70 to 1.12, P = 0.31). Incidence of hyperthermia was significantly higher in the plastic wrap group as compared to that in the control group (RR = 2.55, 95% CI: 1.56 to 4.15, P = 0.0002). Hyperthermia in the plastic wrap group was resolved within one or two hours after unwrapping the babies. Conclusion: Plastic wrap can be considered an effective and safe additional intervention to prevent hypothermia in preterm infants. However, its cost-effectiveness and long-term effect on mortality needs to be ascertained by conducting well-designed studies with longer follow-up period. © 2016 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Tu S.,Chongqing Medical University | Tu S.,Ministry of Education Key Laboratory of Child Development and Disorders | Wang X.,Chongqing Medical University | Bai L.,Chongqing Medical University | And 7 more authors.
Journal of Vascular Access | Year: 2012

Purpose: Report the procedural complications of internal jugular vein (IJV) catheter insertion in infants and children and discuss how to prevent them. Methods: An observational study was performed from January 2006 to August 2010; 1309 internal jugular vein cannulae were inserted in the operating room by either staff or resident anesthesiologists. Patient age, weight, sex, type of catheter (diameter, lumen number), number of attempts, and complications were recorded. The discussion is focused on how to prevent or reduce internal jugular vein line insertion related complications in infants and children. Results: 1309 IJV cannulae were inserted, 85.63% of catheters placed were successful after one to three attempts. Complications included 12 arrhythmias (0.91%), 25 arterial punctures (1.90%), 16 hematomas (1.22%), 17 device occlusions, breaks or malpositions (1.29%), 11 line-related infections (0.84%), four cases of thrombus (0.31%), two cardiopulmonary arrests (0.15%), two hemothoraces (0.15%), five pneumothoraces (0.38%), and one guidewire winding (0.07%). The complication rates of resident anesthesiologists were significantly higher compared to staff anesthesiologists for both common and rare complications (4.27% versus 2.21%; 0.68% versus 0.07%, respectively). In addition, residents' number of attempts were greater than staff anesthesiologists (1.84 and 1.38, respectively). Conclusions: The IJV catheterization was feasible in infants and children. To reduce the risk of complications, the procedure should be performed or supervised by staff anesthesiologists; inserting the needle, guidewire, dilator, and the catheter too far should be avoided. It is now commonly accepted that all central venous cannulations should be performed under ultrasound guidance, especially in children. © 2011 Wichtig Editore.

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