In the peripheral blood mononuclear cells (PBMCs) of HCV infected patients the expression of STAT1 and IRF-1 is downregulated while that of caspase-3 upregulated.

Several peripheral blood mononuclear cell (PBMC) defects have been linked with hepatitis C virus (HCV) infection, including alterations in cytokine secretion and increased cell death. This study was performed to investigate the expression levels of signal transducer and activator of transcription 1 (STAT1), interferon regulatory factor 1 (IRF-1), and caspase 3 in PBMCs of patients infected with HCV. STAT1, IRF-1, and caspase 3 expression levels were compared in PBMCs from 19 untreated (naïve) HCV+ patients, 8 treated (sustained responder [SR]) HCV patients, and 20 HCV- healthy controls. Moreover, PBMCs from naïve HCV+ patients and SR-HCV patients were also evaluated for HCV RNA expression. The expression levels of STAT-1 and IRF-1 were significantly downregulated in PBMCs from naïve HCV+ patients (P  Keywords: PBMC; hepatitis C virus; STAT1; IRF-1; caspase-3.

The Influence of Cytomegalovirus on Expression of HLA-G and its Ligand KIR2DL4 by Human Peripheral Blood Leucocyte Subsets.

HLA-G is a non-classical class I HLA antigen, normally expressed in high levels only on extravillous cytotrophoblast. It has immunosuppressive properties in pregnancy and has also been found to be upregulated on leucocytes in viral infection. In this study, proportions of all leucocyte subsets expressing HLA-G were found to be low in healthy subjects positive or negative for cytomegalovirus (CMV). Significantly greater proportions of CD4+ CD69+ and CD56+ T cells expressed HLA-G compared to other T cells. However, following stimulation with CMV antigens or intact CMV, proportions of CD4+, CD8+, CD69+ and CD56+ T cells, and also B cells expressing HLA-G, were significantly increased in CMV+ subjects. Despite some subjects having alleles of HLA-G associated with high levels of expression, no relationship was found between HLA-G genotype and expression levels. Purified B cells from CMV+ subjects stimulated in mixed culture with CMV antigens showed significantly increased HLA-G mRNA expression by real-time polymerase chain reaction. Serum levels of soluble HLA-G were similar in CMV- and CMV+ subjects but levels in culture supernatants were significantly higher in cells from CMV+ than from CMV- subjects stimulated with CMV antigens. The HLA-G ligand KIR2DL4 was mainly expressed on NK cells and CD56+ T cells with no differences between CMV+ and CMV- subjects. Following stimulation with IL-2, an increase in the proportion of CD56+ T cells positive for KIR2DL4 was found, together with a significant decrease in CD56dimCD16+ NK cells. The results show that CMV influences HLA-G expression in healthy subjects and may contribute to viral immune evasion.

Circulating Levels of the Adipokines Monocyte Chemotactic Protein-4 (MCP-4), Macrophage Inflammatory Protein-1ß (MIP-1ß), and Eotaxin-3 in Severe Obesity and Following Bariatric Surgery.

The aim of the study was to investigate the involvement of the adipokines eotaxin-3, MIP-1ß, and MCP-4 in obesity and related comorbidities and the modification of their circulating levels after bariatric surgery. Eighty severely obese subjects and 20 normal-weight controls were included in the study. Circulating levels of MCP-4, MIP-1ß, and eotaxin-3, and the main clinical, biochemical, and instrumental parameters for the evaluation of cardiovascular and metabolic profile were determined in controls and in obese subjects at baseline and 10 months after surgery. Within the obese group at baseline, eotaxin-3 levels were higher in males than females and in smokers than non-smokers and showed a positive correlation with LDL-cholesterol, apolipoprotein B, and leptin. MIP-1ß showed a positive correlation with age and leptin and a negative correlation with adiponectin and was an independent predictor of increased carotid artery intima-media thickness. MCP-4 levels were higher in obese subjects than controls and showed a positive correlation with body mass index, eotaxin-3, and MIP-1ß. Bariatric surgery induced a marked decrease in all the 3 adipokines. MCP-4 is a novel biomarker of severe obesity and could have an indirect role in favoring sub-clinical atherosclerosis in obese patients by influencing the circulating levels of eotaxin-3 and MIP-1ß, which are directly related to the main atherosclerosis markers and risk factors. The reduction of circulating levels of MCP-4, eotaxin-3, and MIP-1ß could be one of the mechanisms by which bariatric surgery contributes to the reduction of cardiovascular risk in these patients.

ß-Catenin accumulation and S33F mutation of CTNNB1 gene in colorectal cancer in Saudi Arabia.

Several risk factors associated with colorectal cancer (CRC) have been identified including ß-catenin/CTNNB1 hotspot mutations. The levels of ß-catenin within a cell are regulated via phosphorylation of the N terminus of ß-catenin by GSK-3ß. Thus far three serines (S33, 37, 45) and one threonine (T41) are considered to be the substrates for GSK-3ß phosphorylation. In the present investigation an attempt was made to study the role of ß-catenin mutations in exon-3 in 60 colorectal cancer patients from Kingdom of Saudi Arabia (KSA). The hot spot mutation region of ß-catenin exon 3 was evaluated in matched tumor and normal tissues using PCR and direct sequencing. Sequencing of exon 3 of the CTNNB1 gene revealed an activating mutation (S33F) in one of the tumor samples as compared to the normal tissue from the same patient where there was no such mutation found. Immunohistochemical staining showed the accumulation of ß-catenin protein both in cytoplasm and in the nuclei of cancer cells as compared to normal tissue.

The Impact of Human Mammary Tumor Virus (HMTV) on the Expression of Epidermal Growth Factor Receptor (EGFR) and Death-Domain Associated Protein (DAXX) in Breast Carcinoma Tissues.

The presence and characteristics of HMTV in Iraqi breast cancer women are still unknown. Furthermore, the identification of HMTV in human breast carcinoma tissue of patients differs by country, and the factors that influence it are still unknown. In many epithelial tumor types, the EGFR and its signaling pathways outcomes are necessary for the behavior of cells and regulating their proliferation, and it has been discovered that DAXX has strong carcinogenic characteristics and could be a new treatment target. This case-control retrospective study investigated the presence of HMTV in paraffin-embedded blocks (FFPT) of tumor samples from 60 Iraqi women patients diagnosed with primary breast cancer and 20 cases of benign tumors as a control group. HMTV env sequences were identified by Real-time PCR. EGFR and DAXX expression were immun0-detected by the immuno-histochemistry technique. HMTV sequences were detected in 15 (25%) samples of malignant breast tumors and 8 (40%) samples of benign breast tumors. There was no statistically significant association between the detection of env sequences of HMTV and age, grade, hormone receptors, EGFR, or DAXX expression compared to clinicopathological characteristics. However, statistically, the data showed a highly significant difference in the Expression of EGFR between study groups, age, and histological types (P=0.0001), and a significant negative association was observed between EGFR and both Her2 and TNBC. There was a statistically significant difference between DAXX (+) and DAXX (-) in study groups (P=0.002), and it was significantly associated with age and histological types of breast cancer (P=0.031 and 0.007, respectively). No significant association was found between DAXX and EGFR, grade, Her2. TNBC of breast cancer. The current study found HMTV env sequences in breast tumors of Iraqi women, suggesting that a larger sample size is needed to illustrate the potential causative role of HMTV in the development of human breast malignancy. Moreover, a negative association was found between HMTV and DAXX and EGFR Expression.

BeO nanotube as a promising material for anticancer drugs delivery system.

In this research, the application of BeO nanotube (BeONT) as a nanocarrier for Fluorouracil (5-FU) anticancer drug has been studied by density functional theory (DFT) approach. The method ωB97XD with 6-31 G** basis set were employed. A precise surface study, shows that there are two directions for 5-FU adsorption that did not deliver any of the imaginary frequency vibrational spectra, identifying that all relaxation structures are at the lowest energy level. Based on our calculations, the energy of adsorption for 5FU@BeONT structures are range -120 to -168 kJ/mol, in the gas phase and -395 to 4-00 kJ/mol in the aqueous phase. The highest and the lowest values of adsorption energy are both in strong physical adsorption. Due to receiving an electronic charge from 5-FU, BeONT exhibited a p-type semiconducting feature for all positions. In addition, based on natural bond orbital (NBO) analysis, the direction of charge transfer was from fluorine's σ orbitals of the drug to n* orbitals (O and Be atoms) of BeONT with a considerable amount of transferred energy. BeONT can be employed as a potential strong carrier for 5-FU drugs for practical purposes based on our findings.

Application of zinc oxide nano-tube as drug-delivery vehicles of anticancer drug.

CONTEXT: Zinc oxide nano-tube (ZnONT) nano-structures, which possess chemical stability and non-toxicity in the human body, are considered promising for delivering different drugs. Within this work, we scrutinized the drug delivery capability of the ZnONT and its adsorptional properties as a drug delivery vehicle (DDV) for hydroxyurea (HU) as an anti-cancer drug through density functional theory along with the solvent impacts. Based on the optimized structures, it can be suggested that Zn atoms of ZnONT are the ideal sites on this nano-tube for the adsorption of HU. HU had a strong physical adsorption through the O atom of carbonyl groups onto the local pyramidal site of the ZnONT. At 1.96 Å and Ead of -39.28 kcal/mol, in the configuration which was favorable in terms of energy, there was an interaction between the O atoms of -C=O group of the drug and a Zn atom of the ZnONT. In order to scrutinize the excited state properties of the HU-ZnONT complex, we also examined the UV/Vis data of the HU/ZnONT interaction system. Following the adsorption of HU onto the surface of the ZnONT, there was a significant red-shift based on the maximum absorption wavelength, showing that the ZnONT is an ideal candidate for optic sensors in order to detect and monitor the drug molecule. HU could be released in the cancer tissues where pH was low based on the drug release mechanism. The current work thoroughly investigated the mechanism of interaction between the ZnONT and HU, showing that ZnONT can be used for the smart drug delivery of HU. Overall, the findings suggest that ZnONT could be used as an efficient drug-delivery system for the HU drug to treat various types of cancer. METHODS: In this work we used B3LYP-gCP-D3 functional and the basis set LANL2DZ on the transition metal (Zn) and the basis set cc-pVDZ on the others. GAMESS software program was employed for performing the calculations. we performed analyses, including charge transport, molecular electrostatic potential surface (MEP), energetic, electronic, natural bond orbitals (NBOs), and structural optimizations.

Management and outcomes in digestive cancer surgery: design and initial results of a multicenter cohort study.

BACKGROUND: most studies that analyze the influence of structure factors on clinical outcomes are retrospective, based on clinical-administrative databases, and mainly focusing on surgical volume. OBJECTIVE: to study variations in the process and outcomes of oncologic surgery for esophagus, stomach, pancreas, liver metastases and rectum cancers in Catalonia, as well as the factors associated with these variations. PATIENTS AND METHOD: a retrospective (2002) and prospective (2003-05) multicenter cohort study. Data forms were designed to collect patient, process, and care outcome characteristics before surgery, at hospital discharge, and at 3 and 6 months after discharge. Main outcome measures were hospital and follow-up mortality, complications, re-interventions, and relapse rates. RESULTS: 49 hospitals (80%) participated in the retrospective phase, 44 of which (90%) also participated in the prospective phase: 3,038 patients (98%) were included. No differences were observed in the profile of operated patients according to hospital level of complexity, but clinical-pathological staging and other functional status variables could not be assessed because of over 20% of missing values. There was significant variability in the volume of interventions as well as in certain aspects of the healthcare process depending on type of cancer and center complexity. High rates of esophageal cancer mortality (18.2% at discharge, 27.3% at 6 months) and of complications and re-interventions for all cancers assessed, especially rectal cancer (18.4% re-interventions at 6 months), were identified. CONCLUSIONS: the study of the variability identified will require adequate risk-adjustment and should take into account different structure factors. It is necessary that information included in medical records be improved.

A new model for fetal programming: maternal Ramadan-type fasting programs nephrogenesis.

The effect of maternal Ramadan-type fasting (RTF) on the outcome of pregnancy, kidney development and nephron number in male rat offspring was investigated in current study. Pregnant rats were given food and water ad libitum during pregnancy (control) or restricted for 16 h per day (RTF). Kidney structure was examined during fetal life, at birth, and in early and late adulthood. Maternal body weight, food intake, relative food intake and plasma glucose levels were significantly lower (P<0.001) in the RTF group. Litter and pup weights also were significantly lower (P<0.05) in the RTF group at birth, with no difference in the litter size. The RTF group had a longer gestation, delayed nephrogenesis with less well-differentiated glomeruli, more connective tissue, fewer medullary rays, an increase in the nephrogenic zone/cortical zone ratio, and significant increase (P<0.001) in kidney apoptosis at birth. On the other hand, maternal fasting reduced nephron number (by ~31%) with unchanged kidney and total glomerular volumes. Mean glomerular volume was significantly higher in RTF offspring. Assessment of renal structure revealed mild glomerulosclerosis with enlarged lobulated glomeruli in the renal cortex and high interstitial fibrosis in the medulla of RTF kidneys. Taken together, gestational fasting delays nephrogenesis and reduces nephron number in the kidneys of the offspring, that could be partially owing to increased apoptosis.

Proceso asistencial y resultados en la cirugía de cáncer digestivo: diseño y resultados iniciales de un estudio de cohortes multicéntrico / Management and outcomes in digestive cancer surgery: design and initial results of a multicenter cohort study

Antecedentes: la mayoría de estudios que analizan la influenciade factores de estructura sobre los resultados son retrospectivos,realizados con bases de datos clínico-administrativas y basadosprincipalmente en el volumen de intervenciones.Objetivo: estudiar la variabilidad en el proceso y los resultadosde la cirugía oncológica de esófago, estómago, páncreas, metástasishepáticas y recto en Cataluña, así como los factores asociadosa esta.Pacientes y método: estudio de cohortes multicéntrico retrospectivo(2002) y prospectivo (2003-05). Se recogió informaciónsobre el paciente, el proceso y los resultados de la atenciónpreviamente a la cirugía, al alta, y a los 3 y 6 meses.Resultados: participaron 49 (80%) hospitales en la etapa retrospectiva,de los cuales 44 (90%) prosiguieron en la prospectiva.Se incluyeron 3.038 pacientes (98%). No se observaron diferenciasen el perfil de pacientes operados según el nivel de complejidaddel hospital pero no se pudo analizar el estadiaje clínico-patológicoy otras variables de estado funcional por presentar más del20% de valores ausentes. Existió una variabilidad importante en elvolumen de intervenciones por centro así como en algunos aspectosdel proceso asistencial según el tipo de cáncer y la complejidaddel centro. Se identificaron elevadas tasas de mortalidad en esófago(18,2% al alta, 27,3% a los 6 meses) y de complicaciones yreintervenciones en todos los cánceres evaluados, especialmenteen cáncer de recto (18,4% de reintervenciones a los 6 meses).Conclusiones: el estudio de la variabilidad identificada requeriráun adecuado ajuste del riesgo y debería tener en cuenta diferentesfactores de estructura. Es necesario mejorar la informaciónrecogida en la historia clínica(AU)

Background: most studies that analyze the influence of structurefactors on clinical outcomes are retrospective, based on clinical-administrative databases, and mainly focusing on surgical volume.Objective: to study variations in the process and outcomes ofoncologic surgery for esophagus, stomach, pancreas, liver metastasesand rectum cancers in Catalonia, as well as the factors associatedwith these variations.Patients and method: a retrospective (2002) and prospective(2003-05) multicenter cohort study. Data forms were designedto collect patient, process, and care outcome characteristicsbefore surgery, at hospital discharge, and at 3 and 6 monthsafter discharge. Main outcome measures were hospital and followupmortality, complications, re-interventions, and relapse rates.Results: 49 hospitals (80%) participated in the retrospectivephase, 44 of which (90%) also participated in the prospectivephase: 3,038 patients (98%) were included. No differences wereobserved in the profile of operated patients according to hospitallevel of complexity, but clinical-pathological staging and otherfunctional status variables could not be assessed because of over20% of missing values. There was significant variability in the volumeof interventions as well as in certain aspects of the healthcareprocess depending on type of cancer and center complexity. Highrates of esophageal cancer mortality (18.2% at discharge, 27.3%at 6 months) and of complications and re-interventions for all cancersassessed, especially rectal cancer (18.4% re-interventions at6 months), were identified.Conclusions: the study of the variability identified will requireadequate risk-adjustment and should take into account differentstructure factors. It is necessary that information included in medicalrecords be improved(AU)