Loss of IGF2 imprinting is associated with abrogation of long-range intrachromosomal interactions in human cancer cells.

Nuclear architecture and chromatin geography are important factors in the regulation of gene expression, as these components may play a vital epigenetic role both in normal physiology as well as in the initiation and progression of malignancies. Using a modification of the chromosome conformation capture (3C) technique, we examined long-range chromatin interactions of the imprinted human IGF2 gene. We demonstrate that numerous intrachromosomal interactions occur along both parental alleles in normal tissues, where the IGF2 is paternally expressed, as well as in normal liver where gene expression is biallelic. Long-range and allele-specific interactions occur between the IGF2/H19 imprinting control region-1 (ICR1) and ICR2, a region which regulates an imprinted gene cluster nearly a megabase distant from IGF2. Loss of genomic imprinting is a common epigenetic event in cancer, and long-range interactions have not been examined in malignant cells. In cancer cell lines in which IGF2 imprinting is maintained (MOI), essentially all of the 3C interactions seen in normal cells were preserved. However, in cells in which IGF2 imprinting was lost (LOI), nearly all of the long-range chromatin interactions involving IGF2 were abrogated. A three-dimensional computer model depicts the physical interactions between the IGF2 promoter and ICR1 in MOI cells, while the model of LOI lung cancer cells is flattened with few long-range interactions. This dramatic change in the three-dimension configuration of the chromatin at the IGF2 locus in LOI cancer cells suggests that the loss of imprinting may lead to a variety of changes in gene expression in addition to changes in IGF2 transcription.

Changing of serum metabolic hormone and liver size during acute phase of severe adult burn patients.

The aims of this study were to determine characteristics and factors influencing metabolic hormones including serum catecholamines, cortisol level and liver size in severe adult burn patients. A prospective study was conducted on 44 adult burn patients with burn extent from and over 20% TBSA admitted during 72 h after burn to burn intensive care unit, National Burn Hospital, Vietnam. Serum levels of epinephrine, norepinephrine and cortisol were measured on admission and 7th day after burn. Liver size was measured by ultrasound on admission and 21st day after burn. The results indicated that norepinephrine level did not significantly change along the time meanwhile epinephrine concentration significantly increased after 1 week (P < 0.01). Serum cortisol level was higher than normal physiological value and then significantly reduced at 7th day post burn (P < 0.05). Significantly increased liver size was seen at the 21st day postburn (P < 0.01). Age, gender, burn severity, inhalation injury and death did not affect concentration of catecholamines and liver size. Meanwhile, cortisol level was significantly higher in patients with deep burn area ≥ 20% TBSA at 7th day after burn and in non-survivors (P < 0.05). Further studies are necessary to understand clearly metabolic state in severe adult burn patients.

Profile and factors influencing resting energy expenditure in adult burn patients.

The aims of this study are to determine characteristics and factors influencing REE in adult severe burn patients. A prospective study was conducted on 62 adult burn patients admitted during 72 h after burn to burn intensive care unit, National Burn Hospital, Vietnam. REE measurements and REE/BMR calculations were obtained on the 3rd, 7th, 14th, 21st and 28th day after burn. Collected data was analyzed to find out the influence of age, gender, burn extent, inhalation injury to REE. The results indicated that all measured REE was significantly higher than BMR at all time points (REE/BMR ratio > 1) with a peak value on the 7th day then steady decreased but still around 200% in compared with BMR on the 28th day after burn. In compared with females, REE of male patients were significantly higher during the first three weeks after burn. In addition, significantly greater REE were seen in the patients with burn surface area ≥ 60% TBSA or deep burn area ≥ 20% TBSA. Moreover, REE of nonsurvivors was significantly higher in compared with survivor group on the 7th and 14th day after burning. Meanwhile, increased age and presence of inhalation injury did not affect REE. In conclusion, in adult burn patients, increased REE is prolonged, burn size dependent and significantly higher in male and in nonsurvivor. This finding should be considered in nutritional caring for adult burn patients.

The Treatment of Congenital Nasolacrimal Duct Obstruction in Children: A Retrospective Review.

PURPOSE: To compare success and extrusion rates of the monocanalicular and bicanalicular Crawford intubation systems (JEDMED Instrument Company, St. Louis, MO). METHODS: A retrospective review of all children who were diagnosed as having congenital nasolacrimal duct obstruction and treated with lacrimal intubation from 2005 to 2014 was performed. The total number of eyes included was 168 (75 and 93 right and left eyes, respectively). Bicanalicular intubation was used in 80 eyes (bicanalicular group) and monocanalicular intubation was used in 88 eyes (monocanalicular group). RESULTS: Success occurred in 63 (78.75%) and 82 (93.18%) eyes in the bicanalicular and monocanalicular groups, respectively (P = .00653). Extrusion occurred in 24 (30%) and 11 (12.5%) eyes, respectively (P = .00528). CONCLUSIONS: Monocanalicular intubation for congenital nasolacrimal duct obstruction is superior to bicanalicular intubation. Extrusion and reoperation rates are significantly lower. [J Pediatr Ophthalmol Strabismus. 2018;55(1):65-67.].

Glial-derived growth factor and pleiotrophin synergistically promote axonal regeneration in critical nerve injuries.

The repair of nerve gap injuries longer than 3 cm is limited by the need to sacrifice donor tissue and the morbidity associated with the autograft gold standard, while decellularized grafts and biodegradable conduits are effective only in short nerve defects. The advantage of isogenic nerve implants seems to be the release of various growth factors by the denervated Schwann cells. We evaluated the effect of vascular endothelial growth factor, neurotrophins, and pleiotrophin (PTN) supplementation of multi-luminal conduits, in the repair of 3 and 4 cm nerve gaps in the rabbit peroneal nerve. In vitro screening revealed a synergistic regenerative effect of PTN with glial-derived neurotrophic factor (GDNF) in promoting sensory axon density, and motor axonal growth from spinal cord explants. In vivo, pleiotrophins were able to support nerve regrowth across a 3 cm gap. In the 4 cm lesions, PTN-GDNF had a modest effect in the number of axons distal to the implant, while increasing the mean axon diameter (1 ±â€¯0.4; p ≤ 0.001) over PTN or GDNF alone (0.80 ±â€¯0.2, 0.84 ±â€¯0.5; respectively). Some regenerated axons reinnervated muscle targets as indicated by neuromuscular junction staining. However, many were wrapped in Remak bundles, suggesting a delay in axonal sorting, explaining the limited electrophysiological function of the reinnervated muscle, and the modest recovery in toe spreading in the PTN-GDNF repaired animals. These results support the use of synergistic neurotrophic/pleiotrophic growth factors in long gap repair and underscore the need for re-myelination strategies distal to the injury site. STATEMENT OF SIGNIFICANCE: Nerve injuries due to trauma or tumor resection often result in long gaps that are challenging to repair. The best clinical option demands the use of autologous grafts that are associated with serious side effects. Bioengineered nerves are considered a good alternative, particularly if supplemented with growth factors, but current options do not match the regenerative capacity of autografts. This study revealed the synergistic effect of neurotrophins and pleiotrophins designed to achieve a broad cellular regenerative effect, and that GDNF-PTN are able to mediated axonal growth and partial functional recovery in a 4 cm nerve gap injury, albeit delays in remyelination. This report underscores the need for defining an optimal growth factor support for biosynthetic nerve implants.

Thickness of a metallic film, in addition to its roughness, plays a significant role in SERS activity.

In this paper we evaluate the effect of roughness and thickness of silver film substrates, fabricated on glass and polydimethylsiloxane (PDMS) templates, on surface-enhanced Raman Spectroscopy (SERS) activity. While the silver substrates obtained on glass templates exhibit nm-scale roughness, the silver substrates on PDMS templates show larger roughness, on the order of 10 s of nm. These roughness values do not change significantly with the thickness of the silver film. The SERS intensities of 4-aminothiophenol (ATP) deposited on these substrates strongly depend on both roughness and thickness, with more significant contribution from the roughness on thinner films. FEM simulations of the electric field intensities on surfaces of different thicknesses for rough and flat surfaces suggest higher localized plamons on thinner, rough surfaces. This study indicates that, besides roughness, the thickness of the metallic layer plays a significant role in the SERS activity.

Targeted inhibition of tumor proliferation, survival, and metastasis by pentacyclic triterpenoids: potential role in prevention and therapy of cancer.

Over the last two decades, extensive research on plant-based medicinal compounds has revealed exciting and important pharmacological properties and activities of triterpenoids. Fruits, vegetables, cereals, pulses, herbs and medicinal plants are all considered to be biological sources of these triterpenoids, which have attracted great attention especially for their potent anti-inflammatory and anti-cancer activities. Published reports in the past have described the molecular mechanism(s) underlying the various biological activities of triterpenoids which range from inhibition of acute and chronic inflammation, inhibition of tumor cell proliferation, induction of apoptosis, suppression of angiogenesis and metastasis. However systematic analysis of various pharmacological properties of these important classes of compounds has not been done. In this review, we describe in detail the pre-clinical chemopreventive and therapeutic properties of selected triterpenoids that inhibit multiple intracellular signaling molecules and transcription factors involved in the initiation, progression and promotion of various cancers. Molecular targets modulated by these triterpenoids comprise, cytokines, chemokines, reactive oxygen intermediates, oncogenes, inflammatory enzymes such as COX-2, 5-LOX and MMPs, anti-apoptotic proteins, transcription factors such as NF-κB, STAT3, AP-1, CREB, and Nrf2 (nuclear factor erythroid 2-related factor) that regulate tumor cell proliferation, transformation, survival, invasion, angiogenesis, metastasis, chemoresistance and radioresistance. Finally, this review also analyzes the potential role of novel synthetic triterpenoids identified recently which mimic natural triterpenoids in physical and chemical properties and are moving rapidly from bench to bedside research.

Key cell signaling pathways modulated by zerumbone: role in the prevention and treatment of cancer.

Phytochemicals and their synthetic derivatives are making a significant contribution in modern drug discovery programs by targeting several human diseases, including cancer. Most of these natural compounds are often multitargeted in nature, which is generally a very desirable property for cancer therapy, as carcinomas typically involve dysregulation of multiple genes and associated cell-signaling pathways at various stages of initiation, progression and metastasis. Additionally, these natural agents generally have lower side-effects, are readily available and hence are cost effective. One such natural compound is zerumbone, a cyclic eleven-membered sesquiterpene, isolated from the tropical plant Zingiber zerumbet Smith that has attracted great attention recently for its potent anticancer activities in several tumor models. This review summarizes the data based on various in vitro and in vivo studies related to the effects of zerumbone on numerous pivotal molecular targets in cancer and its reported chemopreventive/therapeutic effects in different models of cancer.