Breast cancer classification and prognostication through diverse systems along with recent emerging findings in this respect; the dawn of new perspectives in the clinical applications

Breast cancer is the most common malignancy among women and the second leading cause of mortality due to cancer worldwide. The complexity of breast cancer resembles an intricate ecosystem comprising various cleverly designed interaction levels of internal and external factors to generate a pliable context in the clonal evolution of breast cancer cells. Principally, the complex entity can become evident toward delineating a number of significant variations in the specific fields of breast cancer analyses, including the molecular, physiological, and morphological characteristics, clinical presentations, risk factors, the histopathological conditions, and response to systemic therapy regarding the maintenance of tumor as a whole. In hindsight, various classification systems developing based on specific inclusion criteria have indisputably changed both our appreciation of the biological demeanor of breast cancer and the main strategies for designing tailored therapy regimens through the proper evaluation of diagnosis and prognostication of given specimens. Here, we endeavor to provide a general overview of different types of breast cancer classification as well as the clinical acceptance of their applications along with the latest findings in this area. Taken together, the major significance of breast cancer management that can be ascertained by operational convergent points of its stratification areas is owing to the fact that the achievement of individualized and targeted therapy may denounce new horizons of surveillance and treatment strategies in which they may function as a rheostat of specific therapy regimens toward reducing the detected distances between experimental data and operating options in clinical practice.     

miR-620 promotes tumor radioresistance by targeting 15-hydroxyprostaglandin dehydrogenase (HPGD)

MicroRNA contribute to tumor radiation resistance, which is an important clinical problem, and thus we are interested in identifying and characterizing their function. We demonstrate that miR-620 contributes to radiation resistance in cancer cells by increasing proliferation, and decreasing the G2/M block. We identify the hydroxyprostaglandin dehydrogenase 15-(nicotinamide adenine dinucleotide) (HPGD/15-PGDH) tumor suppressor gene as a direct miR-620 target, which results in increased prostaglandin E2 (PGE2) levels. Furthermore, we show that siRNA targeting of HPGD or administration of exogenous PGE2 recapitulates radioresistance. Targeting of the EP2 receptor that responds to PGE2 using pharmacological or genetic approaches, abrogates radioresistance. Tumor xenograft experiments confirm that miR-620 increases proliferation and tumor radioresistance in vivo. Regulation of PGE2 levels via targeting of HPGD by miR-620 is an innovative manner by which a microRNA can induce radiation resistance.     

In vivo comparison of tantalum,tungsten, and bismuth enteric contrast agents to complement intravenous iodine for double‐contrast dual‐energy CT of the bowel

To assess the ability of dual‐energy CT (DECT) to separate intravenous contrast of bowel wall from intraluminal contrast, we scanned 16 rabbits on a clinical DECT scanner: n = 3 using only iodinated intravenous contrast, and n = 13 double‐contrast enhanced scans using iodinated intravenous contrast and experimental enteric non‐iodinated contrast agents in the bowel lumen (five bismuth, four tungsten, and four tantalum based). Representative image pairs from conventional CT images and DECT iodine density maps of small bowel (116 pairs from 232 images) were viewed by four abdominal imaging attending radiologists to independently score each comparison pair on a visual analog scale (?100 to +100%) for (1) preference in small bowel wall visualization and (2) preference in completeness of intraluminal enteric contrast subtraction. Median small bowel wall visualization was scored 39 and 42 percentage points (95% CI 30–44% and 36–45%, both p < 0.001) higher for double‐contrast DECT than for conventional CT with enteric tungsten and tantalum contrast, respectively. Median small bowel wall visualization for double‐contrast DECT was scored 29 and 35 percentage points (95% CI 20–35% and 33–39%, both p < 0.001) higher with enteric tungsten and tantalum, respectively, than with bismuth contrast. Median completeness of intraluminal enteric contrast subtraction in double‐contrast DECT iodine density maps was scored 28 and 29 percentage points (95% CI 15–31% and 28–33%, both p < 0.001) higher with enteric tungsten and tantalum, respectively, than with bismuth contrast. Results suggest that in vivo double‐contrast DECT with iodinated intravenous and either tantalum‐ or tungsten‐based enteric contrast provides better visualization of small bowel than conventional CT. Copyright © 2016 John Wiley & Sons, Ltd.     

Rabies virus in insectivorous bats: Implications of the diversity of the nucleoprotein and glycoprotein genes for molecular epidemiology

Insectivorous bats are the main reservoirs of rabies virus (RABV) in various regions of the world. The aims of this study were to (a) establish genealogies for RABV strains from different species of Brazilian insectivorous bats based on the nucleoprotein (N) and glycoprotein (G) genes, (b) investigate specific RABV lineages associated with certain genera of bats and (c) identify molecular markers that can distinguish between these lineages. The genealogic analysis of N and G from 57 RABV strains revealed seven genus-specific clusters related to the insectivorous bats Myotis, Eptesicus, Nyctinomops, Molossus, Tadarida, Histiotus and Lasiurus. Molecular markers in the amino acid sequences were identified which were specific to the seven clusters. These results, which constitute a novel finding for this pathogen, show that there are at least seven independent epidemiological rabies cycles maintained by seven genera of insectivorous bats in Brazil.     

Opioid Receptor Blockade Improves Mesenteric Responsiveness in Biliary Cirrhosis

Arterial vasodilation with concomitant hyperdynamic circulation is a common finding in cirrhotic subjects. Elevated levels of plasma endogenous opioid peptides have been reported in cholestasis and cirrhosis. Increased opioid peptides contribute to different manifestations of chronic liver disease such as pruritis, ascitis, and hepatic encephalopathy. In this study the potential role of opioid system in cirrhosis-induced vascular hyporesponsiveness was investigated. Bile duct ligated and sham operated animals received daily subcutaneous administration of naltrexone, an opioid receptor antagonist (20 mg/kg/day), or saline for 28 days. After 4 weeks the superior mesenteric artery was cannulated and was perfused according to McGregor method and then phenylephrine vasoconstrictor response of mesenteric vessels (10⁻¹⁰ to 10⁻⁶ mol) was examined. In order to evaluate the effects of acute opioid receptor blockade, additional groups of animals were treated by acute single intraperitoneal naltrexone injection (20 mg/kg). Plasma level of nitrite/nitrate as an indicator for nitric oxide production was measured. Biliary cirrhosis was accompanied with a decrease in baseline perfusion pressure in mesenteric vascular bed (P < 0.01). Chronic opioid receptor blockade significantly increased this parameter (P < 0.01). The maximum pressure response to phenylephrine was decreased significantly in cirrhosis while chronic naltrexone treatment completely improved it (P < 0.01). Acute single injection of naltrexone could not influence the understudied homodynamic parameters. Chronic opioid receptor blockade did not modulate the increased nitrite/nitrate levels following cholestasis. This study provided evidence on the contribution of endogenous opioid system to vascular hyporesponsiveness in cirrhosis which is not directly correlated to high plasma NO levels.     

Fabrication and performance evaluation of new nanocomposite membranes based on sulfonated poly(phthalazinone ether ketone) for PEM fuel cells

The purpose of this work is to enhance the proton conductivity and fuel cell performance of sulfonated poly(phthalazinone ether ketone) (SPPEK) as a proton exchange membrane through the application of SrTiO₃ perovskite nanoparticles. Nanocomposite membranes based on SPPEK and SrTiO₃ perovskite nanoparticles were prepared via a casting method. The highest proton conductivity of nanocomposite membranes obtained was 120 mS cm⁻¹ at 90 °C and 95% RH. These enhancements could be related to the hygroscopic structure of SrTiO₃ perovskite nanoparticles and the formation of hydrogen bonds between nanoparticles and water molecules. The satisfactory power density, 0.41 W cm⁻² at 0.5 V and 85 °C, of the nanocomposite membrane (5 wt% content of nanoparticles) confirms their potential for application in the PEM fuel cells.

The purpose of this work is to enhance the proton conductivity and fuel cell performance of sulfonated poly(phthalazinone ether ketone) (SPPEK) as a proton exchange membrane through the application of SrTiO₃ perovskite nanoparticles.     

Influence of maternal diabetes on serum leptinemic and insulinemic status of the offspring: A case study of selected patients in a tertiary care hospital in Bangladesh

IntroductionLeptin is now known to be an important hormone affecting intrauterine fetal growth. Since growth of fetus is also affected by the glycemic status of the mother. Serum leptin of infant is influenced by the maternal diabetic state. Investigation of cord blood leptin in babies of DM (Diabetes Mellitus) and GDM (Gestational Diabetes Mellitus) mothers (controlled blood glucose levels) may provide some indication about involvement of genetic factor in the development of leptin abnormalities in fetus.AimThe study was taken to investigate whether cord blood insulin, c-peptide and leptin levels correlate with birth weight in offspring of DM mother.MethodsBlood was drawn from umbilical cord of 30 babies from GDM mothers (GDM-babies), 45 babies from Type 2 DM Mothers (DM-babies), and 30 babies from ND (Nondiabetic) mothers (ND-babies) of term pregnancy. Weight, blood glucose, placenta, serum leptin and c-peptide of the babies were measured.ResultsBirth weight of GDM and DM babies were significantly higher compared to ND-babies. Glucose level in GDM babies was significantly higher than ND and DM babies. Leptin levels in GDM babies were significantly higher than that of ND and DM babies. Serum c-peptide in GDM babies was significantly higher than DM and ND babies. However, there was no significant difference in leptin–glucose ratio among the three groups. Irrespective of degree of hyperglycemia leptin is a major determinant of fetal growth.ConclusionsDM mother produces different insulinemic and leptinemic responses in the fetus indicating a possible genetic involvement.     

冬南瓜醇提物干预雄性大鼠齿状回细胞增殖和空间学习功能的变化

Previous studies reported that some plants,including butternut squash,exert positive effects on the brain.However,few studies have examined the effects of butternut squash on learning,memory,and neurogenesis.This study studied the effects of butternut squash extract on spatial learning and cell proliferation in the dentate gyrus of healthy male rats.Thirty-five male Wistar rats were intrap-eritoneally injected with 0,50,100,200 and 400 mg/kg butternut squash extract once daily for 2 months.After the last administration,rat’s spatial memory was studied using the Morris water maze.Finally,rats were sacrificed and hippocampal sections were prepared for light microscopy and bromodeoxyuridine immunohistochemistry studies.The results revealed that escape latency and swim distance decreased in all treatment groups compared with the control rats,and that the number of bromodeoxyuridine-positive cells in the dentate gyrus was significantly increased in the treatment groups compared with the controls.These findings suggest that butternut squash extract improves the learning and memory abilities of male rats,and increases the proliferation of dentate gyrus cells.