Wound healing and cancer progression in Opisthorchis viverrini associated cholangiocarcinoma

Letter to the editor

O papel da angiogênese e da hemólise na úlcera de perna de pessoas com anemia falciforme

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Differential expression of the eukaryotic release factor 3 (eRF3/GSPT1) according to gastric cancer histological types

Background: There are now several lines of evidence to suggest that protein synthesis and translation factors are involved in the regulation of cell proliferation and cancer development. Aims: To investigate gene expression patterns of eukaryotic releasing factor 3 (eRF3) in gastric cancer. Methods: RNA was prepared from 25 gastric tumour biopsies and adjacent non-neoplastic mucosa. Real time TaqMan reverse transcription polymerase chain reaction (RT-PCR) was performed to measure the relative gene expression levels. DNA was isolated from tumour and normal tissues and gene dosage was determined by a quantitative real time PCR using SYBR Green dye. Results: Different histological types of gastric tumours were analysed and nine of the 25 tumours revealed eRF3/GSPT1 overexpression; moreover, eight of the 12 intestinal type carcinomas analysed overexpressed the gene, whereas eRF3/GSPT1 was overexpressed in only one of the 10 diffuse type carcinomas (Kruskal-Wallis Test; p , 0.05). No correlation was found between ploidy and transcript expression levels of eRF3/GSPT1. Overexpression of eRF3/GSPT1 was not associated with increased translation rates because the upregulation of eRF3/GSPT1 did not correlate with increased eRF1 levels. Conclusions: Overexpression of eRF3/GSPT1 in intestinal type gastric tumours may lead to an increase in the translation efficiency of specific oncogenic transcripts. Alternatively, eRF3/GSPT1 may be involved in tumorigenesis as a result of its non-translational roles, namely (dis)regulating the cell cycle, apoptosis, or transcription.

Anthropometric evaluation and micronutrients intake in patients submitted to laparoscopic Roux-en-Y gastric bypass with a postoperative period of ≥1 year

Backgroung - Bariatric surgery is indicated as the most effective treatment for morbid obesity; the Roux-en-Y gastric bypass (RYGB) is considered the procedure of choice. However, nutritional deficiency may occur in the postoperative period as a result of reduced gastric capacity and change in nutrients absorption in the gastrointestinal tract. The prescription of vitamin and mineral supplementation is a common practice after RYGB; however, it may not be sufficient to prevent micronutrient deficiencies. The aim of this study was to quantify the micronutrient intake in patients undergoing RYGB and verify if the intake of supplementation would be enough to prevent nutritional deficiencies. Methods - The study was conducted on 60 patients submitted to RYGB. Anthropometric, analytical, and nutritional intake data were assessed preoperatively and 1 and 2 years postoperatively. The dietary intake was assessed using 24-h food recall; the values of micronutrients evaluated (vitamin B12, folic acid, iron, and calcium) were compared to the dietary reference intakes (DRI). Results - There were significant differences (p < 0.05) between excess weight loss at the first and second year (69.9 ± 15.3 vs 9.6 ± 62.9 %). In the first and second year after surgery, 93.3 and 94.1 % of the patients, respectively, took the supplements as prescribed. Micronutrient deficiencies were detected in the three evaluation periods. At the first year, there was a significant reduction (p < 0.05) of B12, folic acid, and iron intake. Conclusions - Despite taking vitamin and mineral supplementation, micronutrient deficiencies are common after RYGB. In the second year after surgery, micronutrient intake remains below the DRI.

Translation termination and protein folding pathway genes are not correlated in gastric cancer

Background: The eukaryotic release factor 3 (eRF3) has been shown to affect both tubulin and actin cytoskeleton, suggesting a role in cytoskeleton assembly, mitotic spindle formation and chromosome segregation. Also, direct interactions between eRF3 and subunits of the cytosolic chaperonin CCT have been described. Moreover, both eRF3a and CCT subunits have been described to be up-regulated in cancer tissues. Our aim was to evaluate the hypothesis that eRF3 expression levels are correlated with the expression of genes encoding proteins involved in the tubulin folding pathways. Methods: Relative expression levels of eRF1, eRF3a/GSPT1, PFDN4, CCT2, CCT4, and TBCA genes in tumour samples relative to their adjacent normal tissues were investigated using real time-polymerase chain reaction in 20 gastric cancer patients. Results: The expression levels of eRF3a/GSPT1 were not correlated with the expression levels of the other genes studied. However, significant correlations were detected between the other genes, both within intestinal and diffuse type tumours. Conclusions: eRF3a/GSPT1 expression at the mRNA level is independent from both cell translation rates and from the expression of the genes involved in tubulin-folding pathways. The differences in the patterns of expression of the genes studied support the hypothesis of genetically independent pathways in the origin of intestinal and diffuse type gastric tumours.

On-line self-healing of circuits implemented on reconfigurable FPGAs

To boost logic density and reduce per unit power consumption SRAM-based FPGAs manufacturers adopted nanometric technologies. However, this technology is highly vulnerable to radiation-induced faults, which affect values stored in memory cells, and to manufacturing imperfections. Fault tolerant implementations, based on Triple Modular Redundancy (TMR) infrastructures, help to keep the correct operation of the circuit. However, TMR is not sufficient to guarantee the safe operation of a circuit. Other issues like module placement, the effects of multi- bit upsets (MBU) or fault accumulation, have also to be addressed. In case of a fault occurrence the correct operation of the affected module must be restored and/or the current state of the circuit coherently re-established. A solution that enables the autonomous restoration of the functional definition of the affected module, avoiding fault accumulation, re-establishing the correct circuit state in real-time, while keeping the normal operation of the circuit, is presented in this paper.

A framework for self-healing radiation-tolerant implementations on reconfigurable FPGAs

To increase the amount of logic available in SRAM-based FPGAs manufacturers are using nanometric technologies to boost logic density and reduce prices. However, nanometric scales are highly vulnerable to radiation-induced faults that affect values stored in memory cells. Since the functional definition of FPGAs relies on memory cells, they become highly prone to this type of faults. Fault tolerant implementations, based on triple modular redundancy (TMR) infrastructures, help to keep the correct operation of the circuit. However, TMR is not sufficient to guarantee the safe operation of a circuit. Other issues like the effects of multi-bit upsets (MBU) or fault accumulation, have also to be addressed. Furthermore, in case of a fault occurrence the correct operation of the affected module must be restored and the current state of the circuit coherently re-established. A solution that enables the autonomous correct restoration of the functional definition of the affected module, avoiding fault accumulation, re-establishing the correct circuit state in realtime, while keeping the normal operation of the circuit, is presented in this paper.

A self-healing real-time system based on run-time self-reconfiguration

The new generations of SRAM-based FPGA (field programmable gate array) devices are the preferred choice for the implementation of reconfigurable computing platforms intended to accelerate processing in real-time systems. However, FPGA's vulnerability to hard and soft errors is a major weakness to robust configurable system design. In this paper, a novel built-in self-healing (BISH) methodology, based on run-time self-reconfiguration, is proposed. A soft microprocessor core implemented in the FPGA is responsible for the management and execution of all the BISH procedures. Fault detection and diagnosis is followed by repairing actions, taking advantage of the dynamic reconfiguration features offered by new FPGA families. Meanwhile, modular redundancy assures that the system still works correctly

Gastric acid secretion response in the Cebus apella: a monkey model of chronic Chagas disease

The objective was to study the secretory pattern, both basal and stimulated either by histamine (0.1 mg/kg) or pentagastrin (64 ug/kg) in eighteen Cebus apella monkeys chronically infected with different T. cruzi strains (CA1, n=10; Colombian, n=4 and Tulahuen, n=4) and to describe the morphological findings in the gastrointestinal tract in twelve infected (6 sacrificed and 6 spontaneously dead) and four healthy monkeys. All infected monkeys and 35 healthy ones were evaluated by contrast X-ray examination. No differences were observed in basal acid output between control and infected groups. Animals infected with the Tulahuen and Colombian strains showed significant lower values of peak acid output in response to histamine or pentagastrin (p<0.01 and p<0.05 respectively; "t" test) in comparison to the controls. Barium contrast studies showed enlargement and dilatation of the colon in three infected animals. Histopathological lesions were seen in 75% of the autopsied animals either in colon alone (33%) or both, in colon and esophagus (42%). The normal secretion observed in the CA1 infected group could be due to a lower virulence of the strain, a lower esophagic tropism or the necessity of a longer post-infection time to cause lesions.

Immunohistochemical molecular phenotypes of gastric cancer based on SOX2 and CDX2 predict patient outcome

Background Gastric cancer remains a serious health concern worldwide. Patients would greatly benefit from the discovery of new biomarkers that predict outcome more accurately and allow better treatment and follow-up decisions. Here, we used a retrospective, observational study to assess the expression and prognostic value of the transcription factors SOX2 and CDX2 in gastric cancer. Methods SOX2, CDX2, MUC5AC and MUC2 expression were assessed in 201 gastric tumors by immunohistochemistry. SOX2 and CDX2 expression were crossed with clinicopathological and follow-up data to determine their impact on tumor behavior and outcome. Moreover, SOX2 locus copy number status was assessed by FISH (N = 21) and Copy Number Variation Assay (N = 62). Results SOX2 was expressed in 52% of the gastric tumors and was significantly associated with male gender, T stage and N stage. Moreover, SOX2 expression predicted poorer patient survival, and the combination with CDX2 defined two molecular phenotypes, SOX2+CDX2- versus SOX2-CDX2+, that predict the worst and the best long-term patients’ outcome. These profiles combined with clinicopathological parameters stratify the prognosis of patients with intestinal and expanding tumors and in those without signs of venous invasion. Finally, SOX2 locus copy number gains were found in 93% of the samples reaching the amplification threshold in 14% and significantly associating with protein expression. Conclusions We showed, for the first time, that SOX2 combined with CDX2 expression profile in gastric cancer segregate patients into different prognostic groups, complementing the clinicopathological information. We further demonstrate a molecular mechanism for SOX2 expression in a subset of gastric cancer cases.

Molecular fingerprint of human gastric cell line infected by Helicobacter pylori

Helicobacter pylori infection represents a serious health problem, given its association with serious gastric diseases as gastric ulcers, cancer and MALT lymphoma. Currently no vaccine exists and antibiotic-based eradication therapy is already failing in more than 20% of cases. To increase the knowledge on the infection process diverse gastric cell lines, e.g. the adenocarcinona gastric (AGS) cell line, are routinely used has in vitro models of gastric epithelia. In the present work the molecular fingerprint of infected and non-infected AGS cell lines, by diverse H. pylori strains, was acquired using vibrational infrared spectroscopy. These molecular fingerprints enabled to discriminate infected from non-infected AGS cells, and infection due to different strains, by performing Principal Component Analysis. It was also possible to estimate, from the AGS cells molecular fingerprint, the effect of the infection on diverse biochemical and metabolic cellular status. In resume infra-red spectroscopy enabled the acquisition of infected AGS cells molecular fingerprint with minimal sample preparation, in a rapid, high-throughput, economic process yielding highly sensitive and informative data, most useful for promoting critical knowledge on the H. pylori infection process. © 2015 IEEE.

SHõWA: A Self-healing Framework for Web-based Applications

The complexity of systems is considered an obstacle to the progress of the IT industry. Autonomic computing is presented as the alternative to cope with the growing complexity. It is a holistic approach, in which the systems are able to configure, heal, optimize, and protect by themselves. Web-based applications are an example of systems where the complexity is high. The number of components, their interoperability, and workload variations are factors that may lead to performance failures or unavailability scenarios. The occurrence of these scenarios affects the revenue and reputation of businesses that rely on these types of applications. In this article, we present a self-healing framework for Web-based applications (SHõWA). SHõWA is composed by several modules, which monitor the application, analyze the data to detect and pinpoint anomalies, and execute recovery actions autonomously. The monitoring is done by a small aspect-oriented programming agent. This agent does not require changes to the application source code and includes adaptive and selective algorithms to regulate the level of monitoring. The anomalies are detected and pinpointed by means of statistical correlation. The data analysis detects changes in the server response time and analyzes if those changes are correlated with the workload or are due to a performance anomaly. In the presence of per- formance anomalies, the data analysis pinpoints the anomaly. Upon the pinpointing of anomalies, SHõWA executes a recovery procedure. We also present a study about the detection and localization of anomalies, the accuracy of the data analysis, and the performance impact induced by SHõWA. Two benchmarking applications, exercised through dynamic workloads, and different types of anomaly were considered in the study. The results reveal that (1) the capacity of SHõWA to detect and pinpoint anomalies while the number of end users affected is low; (2) SHõWA was able to detect anomalies without raising any false alarm; and (3) SHõWA does not induce a significant performance overhead (throughput was affected in less than 1%, and the response time delay was no more than 2 milliseconds).

High prevalence of dna from non-H. pylori helicobacters in the gastric mucosa of venezuelan pet dogs and its histological alterations

Non-H. pylori helicobacters (NHPH) have been demonstrated as gastric spiral-shaped bacteria in specimens obtained from dogs; however, their roles in the pathogenesis of upper gastrointestinal disease have not yet been clearly established. The purpose of this study was to evaluate the prevalence of NHPH DNA in the gastric mucosa of dogs and its association with histopathology. Helicobacter was detected through histopathological techniques, PCR, and FISH analysis from fundic biopsies of twenty dogs with or without signs of gastrointestinal disease. PCR and FISH were based on partial 16S rRNA gene sequences. Nineteen dogs showed mild to marked gastritis in the fundus, and only one dog had a healthy gastric mucosa. NHPH DNA was detected in 18 dogs with gastritis and one with normal gastric mucosa. However, there was no significant correlation between the presence of NHPH DNA and the degree of gastritis. These results show a high prevalence of NHPH DNA in the gastric mucosa of dogs from Venezuela. Further studies are necessary to determine a possible association between a specific NHPH species and the degree of gastritis.