Prolyl hydroxylase-1 regulates hepatocyte apoptosis in an NF-κB-dependent manner.

Prolyl hydroxylase-1 regulates hepatocyte apoptosis in an NF-κB-dependent manner.

Biochem Biophys Res Commun. 2016 Apr 26;

Authors: Fitzpatrick SF, Fábián Z, Schaible B, Lenihan CR, Schwarzl T, Rodriguez J, Zheng X, Li Z, Tambuwala MM, Higgins DG, O'Meara Y, Slattery C, Manresa MC, Fraisl P, Bruning U, Baes M, Carmeliet P, Doherty G, von Kriegsheim A, Cummins EP, Taylor CT

Abstract
Hepatocyte death is an important contributing factor in a number of diseases of the liver. PHD1 confers hypoxic sensitivity upon transcription factors including the hypoxia inducible factor (HIF) and nuclear factor-kappaB (NF-κB). Reduced PHD1 activity is linked to decreased apoptosis. Here, we investigated the underlying mechanism(s) in hepatocytes. Basal NF-κB activity was elevated in PHD1(-/-) hepatocytes compared to wild type controls. ChIP-seq analysis confirmed enhanced binding of NF-κB to chromatin in regions proximal to the promoters of genes involved in the regulation of apoptosis. Inhibition of NF-κB (but not knock-out of HIF-1 or HIF-2) reversed the anti-apoptotic effects of pharmacologic hydroxylase inhibition. We hypothesize that PHD1 inhibition leads to altered expression of NF-κB-dependent genes resulting in reduced apoptosis. This study provides new information relating to the possible mechanism of therapeutic action of hydroxylase inhibitors that has been reported in pre-clinical models of intestinal and hepatic disease.

PMID: 27130823 [PubMed - as supplied by publisher]

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The relationship between cortical auditory evoked potentials (CAEPs) and speech perception in children with Nurotron® cochlear implants during four years of follow-up

Publication date: June 2016
Source:International Journal of Pediatric Otorhinolaryngology, Volume 85
Author(s): Qianqian Guo, Yuling Li, Xinxing Fu, Hui Liu, Jing Chen, Chao Meng, Mo Long, Xueqing Chen
ObjectiveThe purpose of the current study was to evaluate the relationship between the presence or absence of cortical auditory evoked potentials (CAEPs) to speech stimuli and the performance of speech perception in Chinese pediatric recipients of the Nurotron^® cochlear implant (CI).We also wanted to determine how the CAEPs might be used as an indicator for predicting early speech perception and could provide objective evidence for clinical applications of CAEPs.Methods23 pediatric unilateral CI recipients participated in this study. 15 males 8 females, and their ages at implantation ranged from 13 to 68 months, with a mean age of 36 months. CAEPs and Mandarin Early Speech Perception (MESP) tests were used to evaluate the audibility and speech perception of these CI users. The tests were administered at the first, second, third, and fourth year after the CI surgery.ResultsAll the subjects demonstrated improvements in detection of speech sounds with CI. The percentages of participants who could detect all three stimuli were 26% (6/23) at first year, to 100% (23/23) at the fourth year post-implantation. The percentages of participants who passed the Category 6 of MESP were from 9% (2/23) at first year, to 91% (21/23) at the fourth year post-implantation. Significant correlations (p<0.05) were found between CAEP scores and MESP at the first, second, third year after the CI surgery. The multiple regression equation for prediction of MESP categories from CAEP scores and hearing ages was MESP=1.088+(0.504×CAEP score)+(0.964×hearing ages) (F=72.919, p<0.001, R²=0.621).ConclusionThe results of this study suggested that aided cortical assessment was a useful tool to evaluate the outcomes of cochlear implantation. Cortical outcomes had a significant positive relationship with the MESP, which predicted the early speech perception of CI recipients.



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Pediatric laryngotracheal separation following a go-cart injury

Publication date: June 2016
Source:International Journal of Pediatric Otorhinolaryngology, Volume 85
Author(s): Polpatt Jitpakdee, Toby Steele, Aditi Bhuskute, Dhave Setabutr
Less than one percent of trauma admission cases are categorized as pediatric neck trauma [13]. Nevertheless, due to an increasingly mobile society, there has been an increasing frequency of pediatric neck trauma with motor vehicle accidents being the most common mechanism of injury [8].We present a case of laryngotracheal separation from a blunt, clothesline injury to the neck in a pediatric patient. We also review the literature and discuss the benefit of balloon airway dilation and its assistance in the management of laryngeal trauma and its resultant effects.



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Protective role of garlic oil against oxidative damage induced by furan exposure from weaning through adulthood in adult rat testis.

Protective role of garlic oil against oxidative damage induced by furan exposure from weaning through adulthood in adult rat testis.

Acta Histochem. 2016 Apr 26;

Authors: El-Akabawy G, El-Sherif NM

Abstract
Furan is produced in a wide variety of heat-treated foods via thermal degradation. Furan contamination is found to be relatively high in processed baby foods, cereal products, fruits juices, and canned vegetables. Several studies have demonstrated that furan is a potent hepatotoxin and hepatocarcinogen in rodents. However, few studies have investigated the toxic effects of furan in the testis. In addition, the exact mechanism(s) by which furan exerts toxicity in the testis has not been fully elucidated. In this study, we investigated the potential of furan exposure from weaning through adulthood to induce oxidative stress in adult rat testis, as well as the potential of garlic oil (GO) to ameliorate the induced toxicity. Our results reveal that furan administration significantly reduced serum testosterone levels and increased the levels of malondialdehyde (MDA); furthermore, furan administration decreased significantly the enzymatic activity of testicular antioxidants, including glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) and induced histopathological alterations in the testis. GO co-administration ameliorated the reduction in testosterone levels and dramatically attenuated the furan-induced oxidative and histopathological changes. In addition, Go significantly down-regulated the increased caspase-3 and cytochrome P450 2E1 (CYP2E1) expression in the furan-treated testis. To the best of our knowledge, this study is the first to demonstrate the furan-induced oxidative changes in the adult rat testis and the protective role of GO to ameliorate these changes through its antioxidant effects and its ability to inhibit CYP2E1 production.

PMID: 27130490 [PubMed - as supplied by publisher]

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Digital image analysis of ossification centers in the axial dens and body in the human fetus.

Digital image analysis of ossification centers in the axial dens and body in the human fetus.

Surg Radiol Anat. 2016 Apr 29;

Authors: Baumgart M, Wiśniewski M, Grzonkowska M, Małkowski B, Badura M, Dąbrowska M, Szpinda M

Abstract
PURPOSES: The detailed understanding of the anatomy and timing of ossification centers is indispensable in both determining the fetal stage and maturity and for detecting congenital disorders. This study was performed to quantitatively examine the odontoid and body ossification centers in the axis with respect to their linear, planar and volumetric parameters.
METHODS: Using the methods of CT, digital image analysis and statistics, the size of the odontoid and body ossification centers in the axis in 55 spontaneously aborted human fetuses aged 17-30 weeks was studied.
RESULTS: With no sex difference, the best fit growth dynamics for odontoid and body ossification centers of the axis were, respectively, as follows: for transverse diameter y = -10.752 + 4.276 × ln(age) ± 0.335 and y = -10.578 + 4.265 × ln(age) ± 0.338, for sagittal diameter y = -4.329 + 2.010 × ln(age) ± 0.182 and y = -3.934 + 1.930 × ln(age) ± 0.182, for cross-sectional area y = -7.102 + 0.520 × age ± 0.724 and y = -7.002 + 0.521 × age ± 0.726, and for volume y = -37.021 + 14.014 × ln(age) ± 1.091 and y = -37.425 + 14.197 × ln(age) ± 1.109.
CONCLUSIONS: With no sex differences, the odontoid and body ossification centers of the axis grow logarithmically in transverse and sagittal diameters, and in volume, while proportionately in cross-sectional area. Our specific-age reference data for the odontoid and body ossification centers of the axis may be relevant for determining the fetal stage and maturity and for in utero three-dimensional sonographic detecting segmentation anomalies of the axis.

PMID: 27130209 [PubMed - as supplied by publisher]

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An Unusual Combination: KRAS and BRAF Co-mutated Metastatic Colorectal Cancer

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Advances of Molecular Targeted Therapy in Gastric Cancer

Abstract

Background

Gastric cancer is the second most common cause of cancer-related death in the world, and its prognosis remains poor with a median overall survival of 12 months for advanced disease. Advances in the understanding of molecular genetics have led to the development of directed molecular targeted therapy in gastric cancer, leading to improve patient outcomes and quality of life.

Discussion

In the treatment of human epidermal growth factor receptor 2 (HER2)-positive gastric cancer, the addition of trastuzumab significantly improves survival in the first-line setting of therapy. Ramucirumab, an antibody directed against vascular endothelial growth factor receptor 2, significantly improved progression-free and overall survival and has been approved for second-line treatment of gastric cancer. Anti-mesenchymal-epithelial transition (c-MET), mammalian target of rapamycin inhibitors, and polo-like kinase 1 inhibitors are under investigation as a novel therapeutic option for the treatment of gastric cancer. The novel therapies target the key immune checkpoint interaction between a T cell co-inhibitory receptor called programmed death 1 (PD-1) and one of its immunosuppressive ligands, PD-L1. This article reviews molecular targeted therapies in gastric cancer, in light of recent advances.

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