Search results for: pancreatic%20adenocarcinoma.

Authors: Xiaodong Li, Peng Gao, Chao-Jung Huang, Shiying Hao, Xuefeng B. Ling, Yongxia Han, Yaqi Zhang, Le Zheng, Chengyin Ye, Modi Liu, Minjie Xia, Changlin Fu, Bo Jin, Karl G. Sylvester, Eric Widen

Abstract:

Predicting the risk of Pancreatic Adenocarcinoma (PA) in advance can benefit the quality of care and potentially reduce population mortality and morbidity. The aim of this study was to develop and prospectively validate a risk prediction model to identify patients at risk of new incident PA as early as 3 months before the onset of PA in a statewide, general population in Maine. The PA prediction model was developed using Deep Neural Networks, a deep learning algorithm, with a 2-year electronic-health-record (EHR) cohort. Prospective results showed that our model identified 54.35% of all inpatient episodes of PA, and 91.20% of all PA that required subsequent chemoradiotherapy, with a lead-time of up to 3 months and a true alert of 67.62%. The risk assessment tool has attained an improved discriminative ability. It can be immediately deployed to the health system to provide automatic early warnings to adults at risk of PA. It has potential to identify personalized risk factors to facilitate customized PA interventions.

Keywords: Cancer prediction, deep learning, electronic health records, pancreatic adenocarcinoma.

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Authors: Darren C-W. Tan, Partha Roy

Abstract:

To determine if the murine insulinoma, β-TC-6, is a suitable substitute for primary pancreatic β-cells in the study of β- cell functional heterogeneity, we used three distinct functional assays to ascertain the cell line-s response to glucose or a glucose analog. These assays include: (i) a 2-NBDG uptake assay; (ii) a calcium influx assay, and; (iii) a quinacrine secretion assay. We show that a population of β-TC-6 cells endocytoses the glucose analog, 2- NBDG, at different rates, has non-uniform intracellular calcium ion concentrations and releases quinacrine at different rates when challenged with glucose. We also measured the Km for β-TC-6 glucose uptake to be 46.9 mM and the Vm to be 8.36 x 10-5 mmole/million cells/min. These data suggest that β-TC-6 might be used as an alternative to primary pancreatic β-cells for the study of glucose-dependent β-cell functional heterogeneity.

Keywords: 2-NBDG, Fura-2/AM, functional heterogeneity, quinacrine.

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Authors: S. Nurdiana, A. S. Nor Haziqah, M. K. Nur Ezwa Khairunnisa, S. Nurul `Izzati, Y. Siti Amna M. J. Norashirene, I. Nur Hilwani

Abstract:

Azadirachta excelsa or locally known as sentang are frequently used as a traditional medicine by diabetes patients in Malaysia. However, less attention has been given to their toxicity effect. Thus, the study is an attempt to examine the protective effect of A. excelsa on the pancreas and to determine possible toxicity mediated by the extract. Diabetes was induced experimentally in rats by high-fat-diet for 16 weeks followed by intraperitoneal injection of streptozotocin at dosage of 35 mg/kg of body weight. Declination of the fasting blood glucose level was observed after continuous administration of A. excelsa for 14 days twice daily. This is due to the refining structure of the pancreas. However, surprisingly, the plant extract reduced the leukocytes, erythrocytes, hemoglobin, MCHC and lymphocytes. In addition, the rat treated with the plant extract exhibited increment in AST and eosinocytes level. Overall, the finding shows that A. excelsa possesses antidiabetic activity by improving the structure of pancreatic islet of Langerhans but involved in ameliorating of hematology and biochemical parameters.

Keywords: Azadirachta excelsa, diabetes, pancreas, hematobiochemical parameters.

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Authors: T. Wresdiyati, S. Sa’diah, A. Winarto

Abstract:

Diabetes mellitus (DM) is a metabolic disease that can be indicated by the high level of blood glucose. The objective of this study was to observe the antidiabetic properties of ethanolic extract of Indonesian Swietenia mahagoni Jacq. seed on the profile of pancreatic superoxide dismutase and β-cells in the alloxan- experimental diabetic rats. The Swietenia mahagoni seed was obtained from Leuwiliang-Bogor, Indonesia. Extraction of Swietenia mahagoni was done by using ethanol with maceration methods. A total of 25 male Sprague dawley rats were divided into five groups; (a) negative control group, (b) positive control group (DM), (c) DM group that was treated with Swietenia mahagoni seed extract, (d) DM group that was treated with acarbose, and (e) non-DM group that was treated with Swietenia mahagoni seed extract. The DM groups were induced by alloxan (110 mg/kgBW). The extract was orally administrated to diabetic rats 500 mg/kg/BW/day for 28 days. The extract showed hypoglycemic effect, increased body weight, increased the content of superoxide dismutase in the pancreatic tissue, and delayed the rate of β-cells damage of experimental diabetic rats. These results suggested that the ethanolic extract of Indonesian Swietenia mahagoni Jacq. seed could be proposed as a potential anti-diabetic agent.

Keywords: β-cell, diabetes mellitus, superoxide dismutase, Swietenia mahagoni.

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Authors: Rauza Sukma Rita, Katsuya Dezaki, Yuko Maejima, Toshihiko Yada

Abstract:

Oxytocin is a nine-amino acid peptide synthesized in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus. Oxytocin promotes contraction of the uterus during birth and milk ejection during breast feeding. Although oxytocin receptors are found predominantly in the breasts and uterus of females, many tissues and organs express oxytocin receptors, including the pituitary, heart, kidney, thymus, vascular endothelium, adipocytes, osteoblasts, adrenal gland, pancreatic islets, and many cell lines. On the other hand, in pancreatic islets, oxytocin receptors are expressed in both α-cells and β-cells with stronger expression in α- cells. However, to our knowledge there are no reports yet about the effect of oxytocin on cytosolic calcium reaction on α and β-cell. This study aims to investigate the effect of oxytocin on α-cells and β-cells and its oscillation pattern. Islet of Langerhans from wild type mice were isolated by collagenase digestion. Isolated and dissociated single cells either α-cells or β-cells on coverslips were mounted in an open chamber and superfused in HKRB. Cytosolic concentration ([Ca2+]i) in single cells were measured by fura-2 microfluorimetry. After measurement of [Ca2+]i, α-cells were identified by subsequent immunocytochemical staining using an anti-glucagon antiserum. In β-cells, the [Ca2+]i increase in response to oxytocin was observed only under 8.3 mM glucose condition, whereas in α-cells, [Ca2+]i an increase induced by oxytocin was observed in both 2.8 mM and 8.3 mM glucose. The oscillation incidence was induced more frequently in β-cells compared to α-cells. In conclusion, the present study demonstrated that oxytocin directly interacts with both α-cells and β-cells and induces increase of [Ca2+]i and its specific patterns.

Keywords: α-cells, β-cells, cytosolic calcium concentration, oscillation, oxytocin.

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Authors: C. S. Mammas, A. Lazaris, A. S. Mamma-Graham, G. Kostopanagiotou, C. Lemonidou, J. Mantas, E. Patsouris

Abstract:

Introduction: The process to build a better safety culture, methods of error analysis, and preventive measures, starts with an understanding of the effects when human factors engineering refer to remote microscopic diagnosis in surgery and specially in organ transplantation for the remote evaluation of the grafts. It has been estimated that even in well-organized transplant systems an average of 8% to 14% of the grafts (G) that arrive at the recipient hospitals may be considered as diseased, injured, damaged or improper for transplantation. Digital microscopy adds information on a microscopic level about the grafts in Organ Transplant (OT), and may lead to a change in their management. Such a method will reduce the possibility that a diseased G, will arrive at the recipient hospital for implantation. Aim: Ergonomics of Digital Microscopy (DM) based on virtual slides, on Telemedicine Systems (TS) for Tele-Pathological (TPE) evaluation of the grafts (G) in organ transplantation (OT). Material and Methods: By experimental simulation, the ergonomics of DM for microscopic TPE of Renal Graft (RG), Liver Graft (LG) and Pancreatic Graft (PG) tissues is analyzed. In fact, this corresponded to the ergonomics of digital microscopy for TPE in OT by applying Virtual Slide (VS) system for graft tissue image capture, for remote diagnoses of possible microscopic inflammatory and/or neoplastic lesions. Experimentation included: a. Development of an OTE-TS similar Experimental Telemedicine System (Exp.-TS), b. Simulation of the integration of TS with the VS based microscopic TPE of RG, LG and PG applying DM. Simulation of the DM based TPE was performed by 2 specialists on a total of 238 human Renal Graft (RG), 172 Liver Graft (LG) and 108 Pancreatic Graft (PG) tissues digital microscopic images for inflammatory and neoplastic lesions on four electronic spaces of the four used TS. Results: Statistical analysis of specialist‘s answers about the ability to diagnose accurately the diseased RG, LG and PG tissues on the electronic space among four TS (A,B,C,D) showed that DM on TS for TPE in OT is elaborated perfectly on the ES of a Desktop, followed by the ES of the applied Exp.-TS. Tablet and Mobile-Phone ES seem significantly risky for the application of DM in OT (p<.001). Conclusion: To make the largest reduction in errors and adverse events referring to the quality of the grafts, it will take application of human factors engineering to procurement, design, audit, and aware ness-raising activities. Consequently, it will take an investment in new training, people, and other changes to management activities for DM in OT. The simulating VS based TPE with DM of RG, LG and PG tissues after retrieval; seem feasible and reliable and dependable on the size of the electronic space of the applied TS, for remote prevention of diseased grafts from being retrieved and/or sent to the recipient hospital and for post-grafting and pre-transplant planning.

Keywords: Organ Transplantation, Tele-Pathology, Digital Microscopy, Virtual Slides.

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Authors: Meisam Omidi, M. Mirijalili, Mohammadmehdi Choolaei, Z. Sharifi, F. Haghiralsadat, F. Yazdian

Abstract:

In this work, we have used arrays of micromechanical piezoresistive cantilever with different geometries to detect carcinoembryonic antigen (CEA), which is known as an important biomarker associated with various cancers such as colorectal, lung, breast, pancreatic, and bladder cancer. The sensing principle is based on the surface stress changes induced by antigen–antibody interaction on the microcantilevers surfaces. Different concentrations of CEA in a human serum albumin (HSA) solution were detected as a function of deflection of the beams. According to the experiments, it was revealed that microcantilevers have surface stress sensitivities in the order of 8 (mJ/m). This matter allows them to detect CEA concentrations as low as 3 ng/mL or 18 pM. This indicates the fact that the self-sensing microcantilevers approach is beneficial for pathological tests.

Keywords: Micromechanical biosensors, Carcinoembryonic antigen (CEA), surface stress.

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Authors: Surajit Debnath, Soma Addya

Abstract:

Human genome is not only the evolutionary summation of all advantageous events, but also houses lesions of deleterious foot prints. A single gene mutation sometimes may express multiple consequences in numerous tissues and a linear relationship of the genotype and the phenotype may often be obscure. ß Thalassemia minor, a transfusion independent mild anaemia, coupled with environment among other factors may articulate into phenotypic pleotropy with Hypocholesterolemia, Vitamin D deficiency, Tissue hypoxia, Hyper-parathyroidism and Psychological alterations. Occurrence of Pancreatic insufficiency, resultant steatorrhoea, Vitamin-D (25-OH) deficiency (13.86 ngm/ml) with Hypocholesterolemia (85mg/dl) in a 30 years old male ß Thal-minor patient (Hemoglobin 11mg/dl with Fetal Hemoglobin 2.10%, Hb A2 4.60% and Hb Adult 84.80% and altered Hemogram) with increased Para thyroid hormone (62 pg/ml) & moderate Serum Ca+2 (9.5mg/ml) indicate towards a cascade of phenotypic pleotropy where the ß Thalassemia mutation ,be it in the 5’ cap site of the mRNA , differential splicing etc in heterozygous state is effecting several metabolic pathways. Compensatory extramedulary hematopoiesis may not coped up well with the stressful life style of the young individual and increased erythropoietic stress with high demand for cholesterol for RBC membrane synthesis may have resulted in Hypocholesterolemia.Oxidative stress and tissue hypoxia may have caused the pancreatic insufficiency, leading to Vitamin D deficiency. This may in turn have caused the secondary hyperparathyroidism to sustain serum Calcium level. Irritability and stress intolerance of the patient was a cumulative effect of the vicious cycle of metabolic compromises. From these findings we propose that the metabolic deficiencies in the ß Thalassemia mutations may be considered as the phenotypic display of the pleotropy to explain the genetic epidemiology. According to the recommendations from the NIH Workshop on Gene-Environment Interplay in Common Complex Diseases: Forging an Integrative Model, study design of observations should be informed by gene-environment hypotheses and results of a study (genetic diseases) should be published to inform future hypotheses. Variety of approaches is needed to capture data on all possible aspects, each of which is likely to contribute to the etiology of disease. Speakers also agreed that there is a need for development of new statistical methods and measurement tools to appraise information that may be missed out by conventional method where large sample size is needed to segregate considerable effect. A meta analytic cohort study in future may bring about significant insight on to the title comment.

Keywords: Genetic disease, Genetic epidemiology, Heterozygous, Phenotype, Pleotropy, ß Thalassemia minor, Metabolic compromises.

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Authors: Salim Cerig, Fatime Geyikoglu, Pınar Akpulat, Suat Colak, Hasan Turkez, Murat Bakir, Mirkhalil Hosseinigouzdagani, Kubra Koc

Abstract:

This study was designed to evaluate whether carvacrol (CAR) could provide protection against lung injury by acute pancreatitis development. The rats were randomized into groups to receive (I) no therapy; (II) 50 μg/kg cerulein at 1h intervals by four intraperitoneal injections (i.p.); (III) 50, 100 and 200 mg/kg CAR by one i.p.; and (IV) cerulein+CAR after 2h of cerulein injection. 12h later, serum samples were obtained to assess pancreatic function the lipase and amylase values. The animals were euthanized and lung samples were excised. The specimens were stained with hematoxylin-eosin (H&E), periodic acid–Schif (PAS), Mallory's trichrome and amyloid. Additionally, oxidative DNA damage was determined by measuring as increases in 8-hydroxy-deoxyguanosine (8-OH-dG) adducts. The results showed that the serum activity of lipase and amylase in AP rats were significantly reduced after the therapy (p<0.05). We also found that the 100 mg/kg dose of CAR significantly decreased 8-OH-dG levels. Moreover, the severe pathological findings in the lung such as necrosis, inflammation, congestion, fibrosis, and thickened alveolar septum were attenuated in the AP+CAR groups when compared with AP group. Finally, the magnitude of the protective effect on lung is certain, and CAR is an effective therapy for lung injury caused by AP.

Keywords: Antioxidant activity, carvacrol, experimental acute pancreatitis, lung injury, oxidative DNA damage.

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Authors: Ratnakar Tripathi, Rajnikant Mishra

Abstract:

The PAX6, a transcription factor, is essential for the morphogenesis of the eyes, brain, pituitary and pancreatic islets. In rodents, the loss of Pax6 function leads to central nervous system defects, anophthalmia, and nasal hypoplasia. The haplo-insufficiency of Pax6 causes microphthalmia, aggression and other behavioral abnormalities. It is also required in brain patterning and neuronal plasticity. In human, heterozygous mutation of Pax6 causes loss of iris [aniridia], mental retardation and glucose intolerance. The 3- deletion in Pax6 leads to autism and aniridia. The phenotypes are variable in peneterance and expressivity. However, mechanism of function and interaction of PAX6 with other proteins during development and associated disease are not clear. It is intended to explore interactors of PAX6 to elucidated biology of PAX6 function in the tissues where it is expressed and also in the central regulatory pathway. This report describes In-silico approaches to explore interacting proteins of PAX6. The models show several possible proteins interacting with PAX6 like MITF, SIX3, SOX2, SOX3, IPO13, TRIM, and OGT. Since the Pax6 is a critical transcriptional regulator and master control gene of eye and brain development it might be interacting with other protein involved in morphogenesis [TGIF, TGF, Ras etc]. It is also presumed that matricelluar proteins [SPARC, thrombospondin-1 and osteonectin etc] are likely to interact during transport and processing of PAX6 and are somewhere its cascade. The proteins involved in cell survival and cell proliferation can also not be ignored.

Keywords: Interacting Proteins, Pax6, PIP, STRING

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Authors: Wai Prathumpai, Pranee Rachtawee, Sutamat Khajeeram, Pariya Na Nakorn

Abstract:

The  β-glucan produced by Ophiocordyceps dipterigena BCC 2073 is a (1, 3)-β-D-glucan with highly branching O-6-linkedside chains that is resistant to acid hydrolysis (by hydrochloric acid and porcine pancreatic alpha-amylase). This β-glucan can be utilized as a prebiotic due to its advantageous structural and biological properties. The effects of using this β-glucan as the sole carbon source for the in vitro growth of two probiotic bacteria (L. acidophilus BCC 13938 and B. animalis ATCC 25527) were investigated. Compared with the effect of using 1% glucose or fructo-oligosaccharide (FOS) as the sole carbon source, using 1% β-glucan for this purpose showed that this prebiotic supported and stimulated the growth of both types of probiotic bacteria and induced them to produce the highest levels of metabolites during their growth. The highest levels of lactic and acetic acid, 10.04 g·L^-1 and 2.82 g·L^-1, respectively, were observed at 2 h of cultivation using glucose as the sole carbon source. Furthermore, the fermentation broth obtained using 1% β-glucan as the sole carbon source had greater antibacterial activity against selected pathogenic bacteria (B. subtilis TISTR 008, E. coli TISTR 780, and S. typhimurium TISTR 292) than did the broths prepared using glucose or FOS as the sole carbon source. The fermentation broth obtained by growing L. acidophilus BCC 13938 in the presence of β-glucan inhibited the growth of B. subtilis TISTR 008 by more than 70% and inhibited the growth of both S. typhimurium TISTR 292 and E. coli TISTR 780 by more than 90%. In conclusion, O. dipterigena BCC 2073 is a potential source of a β-glucan prebiotic that could be used for commercial production in the near future.

Keywords: β-glucan, Ophiocordyceps dipterigena, prebiotic, probiotic, antimicrobial.

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Authors: Aditya Arya, Hairin Taha, Ataul Karim Khan, Nayiar Shahid, Hapipah Mohd Ali, Mustafa Ali Mohd

Abstract:

This study has investigated the antidiabetic and antioxidant potential of Pseudovaria macrophylla bark extract on streptozotocin–nicotinamide induced type 2 diabetic rats. LCMSQTOF and NMR experiments were done to determine the chemical composition in the methanolic bark extract. For in vivo experiments, the STZ (60 mg/kg/b.w, 15 min after 120 mg/kg/1 nicotinamide, i.p.) induced diabetic rats were treated with methanolic extract of Pseuduvaria macrophylla (200 and 400 mg/kg·bw) and glibenclamide (2.5 mg/kg) as positive control respectively. Biochemical parameters were assayed in the blood samples of all groups of rats. The pro-inflammatory cytokines, antioxidant status and plasma transforming growth factor βeta-1 (TGF-β1) were evaluated. The histological study of the pancreas was examined and its expression level of insulin was observed by immunohistochemistry. In addition, the expression of glucose transporters (GLUT 1, 2 and 4) were assessed in pancreas tissue by western blot analysis. The outcomes of the study displayed that the bark methanol extract of Pseuduvaria macrophylla has potentially normalized the elevated blood glucose levels and improved serum insulin and C-peptide levels with significant increase in the antioxidant enzyme, reduced glutathione (GSH) and decrease in the level of lipid peroxidation (LPO). Additionally, the extract has markedly decreased the levels of serum pro-inflammatory cytokines and transforming growth factor beta-1 (TGF-β1). Histopathology analysis demonstrated that Pseuduvaria macrophylla has the potential to protect the pancreas of diabetic rats against peroxidation damage by downregulating oxidative stress and elevated hyperglycaemia. Furthermore, the expression of insulin protein, GLUT-1, GLUT-2 and GLUT-4 in pancreatic cells was enhanced. The findings of this study support the anti-diabetic claims of Pseudovaria macrophylla bark.

Keywords: Diabetes mellitus, Pseuduvaria macrophylla, alkaloids, caffeic acid.

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