New Aspects of the Epigenetics of Pancreatic Carcinogenesis.

Pancreatic cancer remains among the deadliest forms of cancer with a 5 year survival rate less than 10%. With increasing numbers being observed, there is an urgent need to elucidate the pathogenesis of pancreatic cancer. While both contribute to disease progression, neither genetic nor environmental factors completely explain susceptibility or pathogenesis. Defining the links between genetic and environmental events represents an opportunity to understand the pathogenesis of pancreatic cancer. Epigenetics, the study of mitotically heritable changes in genome function without a change in nucleotide sequence, is an emerging field of research in pancreatic cancer. The main epigenetic mechanisms include DNA methylation, histone modifications and RNA interference, all of which are altered by changes to the environment. Epigenetic mechanisms are being investigated to clarify the underlying pathogenesis of pancreatic cancer including an increasing number of studies examining the role as possible diagnostic and prognostic biomarkers. These mechanisms also provide targets for promising new therapeutic approaches for this devastating malignancy

Management of iron-deficiency anemia following acute gastrointestinal hemorrhage: A narrative analysis and review

Many patients experiencing acute gastrointestinal bleeding (GIB) require iron supplemen-tation to treat subsequent iron deficiency (ID) or iron-deficiency anemia (IDA). Guidelinesregarding management of these patients are lacking. We aimed to identify areas of unmetneed in patients with ID/IDA following acute GIB in terms of patient management andphysician guidance. We formed an international working group of gastroenterologists toconduct a narrative review based on PubMed and EMBASE database searches (fromJanuary 2000 to February 2021), integrated with observations from our own clinical expe-rience. Published data on this subject are limited and disparate, and those relating topost-discharge outcomes, such as persistent anemia and re-hospitalization, are particularlylacking. Often, there is no post-discharge follow-up of these patients by a gastroenterolo-gist. Acute GIB-related ID/IDA, however, is a prevalent condition both at the time of hos-pital admission and at hospital discharge and is likely underdiagnosed and undertreated.Despite limited data, there appears to be notable variation in the prescribing of intravenous(IV)/oral iron regimens. There is also some evidence suggesting that, compared with oraliron, IV iron may restore iron levels faster following acute GIB, have a better tolerabilityprofile, and be more beneficial in terms of quality of life. Gaps in patient care exist inthe management of acute GIB-related ID/IDA, yet further data from largepopulation-based studies are needed to confirm this. We advocate the formulation ofevidence-based guidance on the use of iron therapies in these patients, aiding a more stan-dardized best-practice approach to patient care

An Evaluation of Periodontal Status and Cytokine Levels in Saliva and Gingival Crevicular Fluid of Patients with Inflammatory Bowel Diseases.

AIMS Periodontal diseases and inflammatory bowel diseases (IBD, ulcerative colitis [UC] and Crohn's disease [CD]) have been reported to present with increased salivary and gingival crevicular fluid (GCF) concentrations of cytokines. The aim of this study was to evaluate the salivary and GCF levels of TNF-α, IL-1β, IL-10, and IL-17A and their associations with the periodontal statuses of UC, CD and non-IBD patients, and to analyze the interrelationships among these cytokines, IBD conditions, and periodontal diseases. MATERIALS AND METHODS This cross-sectional study was performed with a total of 131 patients (62 women and 69 men, mean age 42.96±13.02 years). Patients were divided into three groups: UC, CD, and non-IBD. Periodontal status was defined according to the 2017 World Workshop Disease Classification. Salivary and GCF cytokine levels were analyzed using ELISA. RESULTS UC and CD patients diagnosed as having periodontitis and gingivitis presented with significantly higher levels of TNF-α and lower levels of IL-10 as compared with non-IBD patients (p<0.05). UC patients diagnosed with periodontitis exhibited significantly higher scores of bleeding on probing (p = 0.011) and increased salivary and GCF IL-1β levels as compared with CD patients (p = 0.005, and 0.012 respectively). Considering the active and remission status of IBD, salivary IL-1β was found to be correlated with the parameters representing the severity of periodontal diseases in active UC and CD patients. CONCLUSION(S) In the presence of periodontal diseases, UC and CD patients showed different expression levels of TNF-α, IL-1β, and IL-10 in oral secretions as compared with non-IBD patients. This article is protected by copyright. All rights reserved

Improvement of Work Productivity and Quality of Life with Anti-Tumor Necrosis Factor Treatment Used in Crohn's Disease in Routine Clinical Practice in Turkey

Background: Patients with Crohn's disease experience major deterioration in work productivity and quality of life. We aimed to provide the long-term effects of anti-tumor necrosis factor agents on work productivity and activity impairment and quality of life in patients with Crohn's disease using the Inflammatory Bowel Disease Questionnaire and the Short-Form Health Survey-36. Methods: Patients with Crohn's disease and initiated an anti-tumor necrosis factor treatment were included and followed up for 12 months in this observational study. Results: A total of 106 patients were included in this study, and 64.2% of the patients were males. Mean [+/- standard deviation] age was 36.8 [+/- 10.9] years. At baseline, mostly perianal fistulas [65.7%] were observed [n = 23]. Intestinal stenosis was detected in 34.9% of the patients [n = 37], and most of the stenosis was located in the ileum [70.6%] followed by the colon [20.6%]. Extraintestinal symptoms were observed in 24 patients [22.6%]. Most frequent extraintestinal symptom was arthritis with 71.4% [n = 15]. Mean time from first symptom to initiation of anti-tumor necrosis factor treatment was 6.3 [+/- 5.0] years. Improvements in work productivity and activity impairment scores throughout 12 months were -24.1% [P =.003] for work time missed, -18.0% [P =.006] for impairment at work, -8.5% [P =.160] for overall work impairment, and -17.0% [P <.001] for daily activity impairment. Similarly, significant improvements [P <.001] were detected in all components of the Inflammatory Bowel Disease Questionnaire when compared to baseline. Statistically significant improvements [P <.05] were detected for all components of Short-Form Health Survey-36 except for mental health [P =.095]. Conclusion: Our study indicates the significant improvement in work productivity and activity impairment and quality of life of patients with Crohn's disease who receive long-term anti-tumor necrosis factor treatment.AbbVie; Takeda; Genfit; Pfizer; Roche; Janssen; Gilead; Celltrion; UCBThe design, study conduct, and financial support for this study were provided by AbbVie. AbbVie participated in study design, research, analysis and data collection, interpretation of data, and review and approval of this manuscript. All authors received investigator fee payments from AbbVie for participating in this study. In addition, Dr. Murat Toruner has received no research grant, received consulting and/or speaker fee from AbbVie, Amgen, MSD, Takeda, Janssen. Dr. Metin Basaranoglu received research grant from Takeda and Genfit; received speaker and/or consulting fee from AbbVie, MSD, UCB, Bayer, and Santa Farma. Dr. Ozlen Atug received no research grant; received consulting and/or speaker fee from AbbVie, MSD, Takeda, and Eczacibasi. Dr. Filiz Akyuz received research grant from Pfizer and Genfit; consulting fee from Medtronic and speaker fee from AbbVie, Ferring, and Reckitt Benckiser. Dr. Cem Cekic received no research grant and received speaker and/or consultancy fee from AbbVie, Celltrion, and Ferring. Dr. Hulya Over Hamzaoglu received research grant from Roche and Janssen and speaker fee from AbbVie, MSD, Takeda, Ferring and consultancy fees from AbbVie, MSD, Takeda, and Ferring. Dr. Orhan Sezgin received research grant from AbbVie and Gilead and speaker and/or consultancy fees from AbbVie, Abdi Ibrahim, Bilim, Takeda, Ferring, UCB, and Drogsan. Dr. Hale Akpinar received research grant from AbbVie, Celltrion, and Janssen and speaker and/or consultancy fees from Abbvie, Ferring, MSD, Takeda, and UCB. Dr. Aykut Ferhat Celik received research grant from AbbVie, Pfizer, Janssen, UCB, and Takeda and speaker and/or consultancy fees from Abbvie, Ferring, Eczacibasi, Janssen, UCB, and Takeda. Dr. Ahmet Tezel received research grant from Lilly and Pfizer and speaker and/or consultancy fee from AbbVie, Ali Raif, Eczacibasi, Ferring, MSD, Takeda, and Pfizer. Dr. Fatih Tekin, Dr. Omer Senturk, Dr. Huseyin Savas Gokturk, and Dr. Taylan Kav have no additional disclosures to declare

Antianoikis effect of nuclear factor-κb through up-regulated expression of osteoprotegerin, bcl-2, and iap-1

Epithelial cells undergo a form of apoptosis termed anoikis when they lose extracellular attachments. We evaluated the role of transcription factor NF-kappa B in the regulation of anoikis susceptibility of intestinal epithelial cells. Culture of rat intestinal epithelial cells in suspension induced NF-kappa B activation, which blocked the anoikis of those cells, as assessed by internucleosomal DNA fragmentation and caspase-3 cleavage. Activation of NF-kappa B after the loss of extracellular attachments required focal adhesion kinase tyrosine 397 phosphorylation. This triggered a signaling cascade through phosphatidylinositol 3-kinase and AKT, to induce DNA binding of the RelA/p65 NF-kappa B polypeptide. NF-kappa B activated in this manner induced the up-regulated expression of a distinct program of genes that included osteoprotegerin, BCL-2, and IAP-1 ( inhibitor of apoptosis protein-1). Chromatin immunoprecipitation experiments revealed that NF-kappa B directly regulated the promoters of these 3 genes. Knock-down of the expression of osteoprotegerin, BCL-2, or inhibitor of apoptosis protein-1 by RNA interference showed that these factors inhibit anoikis, and genetic reconstitution of their expression alone or in combination restored normal levels of anoikis to NF-kappa B-inactive intestinal epithelial cells. Together, these findings have identified the molecular components of a previously unrecognized antianoikis pathway in intestinal epithelial cells

Insulin Like Growth Factor-I and IGF-Binding Protein-3 Levels in A Healthy Adult Turkish Population

Tuzun, Hakan/0000-0002-6376-8979WOS: 000298720200004Objective: Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) levels are important markers in diagnosis of growth hormone (GH) related disorders. The normal levels of IGF-I and IGFBP-3 vary among different ethnic groups, and using the references derived from different populations may sometimes be misleading during diagnosis, treatment and follow-up. We examined the levels of IGF-I and IGFBP-3 in healthy adult Turkish population. Material and Methods: Eight hundred and thirty-three subjects (512 females, 321 males) were enrolled in the study. Serum IGF-I and IGFBP-3 levels were measured by immunoradiometric assay in all participants. The study population was divided into age groups (18-20, 21-23, 24-25, 26-30, 31-40, 41-50, >50 years of age) and gender groups (females and males separately in the population 30 years of age (p<0.05). Conclusion: Serum IGF-I concentrations of our study population are generally higher than the reference values of the commercial kit. Centers dealing with GH disorders might benefit from defining their own population's normal values for IGF-I and IGFBP-3 to overcome possible diagnostic and follow-up pitfalls