Cancer Causes Control

ObjectiveBlue-collar workers are difficult to reach and less likely to successfully quit smoking. The objective of this study was to test a training site-based smoking cessation intervention.MethodsThis study is a randomized-controlled trial of a smoking cessation intervention that integrated occupational health concerns and was delivered in collaboration with unions to apprentices at 10 sites (n\ua0=\ua01,213). We evaluated smoking cessation at 1 and 6\ua0months post-intervention.ResultsThe baseline prevalence of smoking was 41%. We observed significantly higher quit rates in the intervention versus control group (26% vs. 16.8%; p\ua0=\ua00.014) 1\ua0month after the intervention. However, the effects diminished over time so that the difference in quit rate was not significant at 6\ua0month post-intervention (9% vs. 7.2%; p\ua0=\ua00.48). Intervention group members nevertheless reported a significant decrease in smoking intensity (OR\ua0=\ua03.13; 95% CI: 1.55\u20136.31) at 6\ua0months post-intervention, compared to controls.ConclusionThe study demonstrates the feasibility of delivering an intervention through union apprentice programs. Furthermore, the notably better 1-month quit rate results among intervention members and the greater decrease in smoking intensity among intervention members who continued to smoke underscore the need to develop strategies to help reduce relapse among blue-collar workers who quit smoking.20091R01 DP000097-01/DP/NCCDPHP CDC HHS/United StatesL60 MD003645/MD/NIMHD NIH HHS/United States19301135PMC2694320712

Telomeres and their functions

Na krajevima linearnih kromosoma nalaze se nekodirajući zaštitni sljedovi DNA, telomere. Čine ih kratke ponavljajuće sekvence, npr. TTAGGG kod kralješnjaka, te proteini koji ih štite i sudjeluju u njihovoj funkciji. Jedna od njih jest razlikovanje krajeva kromosoma od dvolančanog loma kako ih stanični mehanizmi (NHEJ) ne bi "popravili" i uzrokovali fuzije kromosoma i nepoželjne rearanžmane koji bi doveli do krize stanice ili raka. Zbog problema replikacije krajeva kromosoma, DNA se skraćuje prilikom svake stanične diobe. Kako se ne bi gubili geni, gube se telomere, sve dok ne dostignu tzv. Hayflickovu granicu kada se stanica prestaje dijeliti zbog nezaštićenih kromosoma. Neke stanice i nestanični organizmi eksprimiraju enzim telomerazu koji produljuje telomere s pomoću svoje proteinske domene i RNA kalupa. Telomerazu eksprimiraju npr. matične stanice, te stanice raka. Potonje su uspjele ugasiti pRB i p53 putove koji dovode do senescencije stanica ili apoptoze, te povećati aktivnost telomeraze kako bi postale besmrtne. Također se koriste i alternativnim putovima produljenja telomera koji uključuju homolognu rekombinaciju. Pretpostavlja se da je senescencija evoluirala kako bi se spriječila tumorigeneza. Znanstvenici su, ipak, uspjeli usporiti starenje miševa s pomoću telomeraze bez povećanja učestalosti stvaranja tumora. Kako je skraćivanje telomera jedan od razloga zašto starimo, u budućim će se istraživanjima možda pronaći način kako da se produži ljudski život. Također, cjepiva za rak temeljena na telomerazi već se testiraju, s uspješnim rezultatima.Telomeres are non-coding protective sequences found at the end of linear chromosomes. They are made of repeating sequences, for example TTAGGG in vertebrates, and proteins that protect them and participate in their function. One of their functions is to distinguish the ends of the chromosomes from double-strand breaks – to prevent a cellular repair mechanism (NHEJ) from 'repairing' them which would lead to chromosome fusion and rearrangements, and, eventually, cell crisis or cancer. Because of the chromosome end replication problem, DNA is shortening with every cell division. In order to preserve genes from eroding, telomeres are the ones that are being lost, for until they reach the Hayflick limit when the cell stops dividing because of unprotected chromosomes. Some cells and noncellular organisms express an enzyme called telomerase which lengthens telomeres with its RNA template and protein domain. Telomerase is expressed, for example, in stem and cancer cells. The later have succeeded to shut down pRB and p53 pathways that would lead to cellular senescence or apoptosis, and to increase the activity of telomerase, making themselves immortal. Cancer cells also use alternative telomere lengthening mechanisms that include homologous recombination. It is assumed that senescence has evolved in a way to prevent tumorigenesis. Scientists, however, have succeeded to slow down ageing in mice with telomerase, without an increase in tumour occurrence. Telomere shortening is one of the reasons why we age, so future research could find a way to expand human lifespan. Additionally, vaccines for cancer based on telomerase are already being tested, with successful results

Promjena CpG metilacije u promotoru gena BACH2 u pacijenata oboljelih od upalnih bolesti crijeva

Crohnova bolest (CD) i ulcerozni kolitis (UC) pripadaju grupi kroničnih bolesti koje karakterizira upala dijelova probavnog sustava, a objedinjene su pod zajedničkim nazivom upalne bolesti crijeva. Etiopatogeneza uključuje disbiozu crijevne mikroflore i poremećaj u funkciji imunološkog sustava. Proteinski produkt gena BACH2 transkripcijski je faktor s važnom ulogom u razvoju, aktivaciji i sazrijevanju B limfocita te regulaciji i senescenciji T limfocita i proizvodnji citokina. Na taj način, BACH2 ima ključnu ulogu u održavanju imunološke homeostaze. Cjelogenomske asocijacijske studije povezale su BACH2 s brojnim autoimunim bolestima, uključujući upalne bolesti crijeva. Cilj ovog istraživanja je analizirati metilaciju DNA u promotoru gena BACH2 iz krvi osoba oboljelih od CD i UC te zdravih osoba. U tu svrhu upotrijebljeno je pirosekvenciranje nakon bisulfitne konverzije DNA te je određen stupanj metilacije CpG dinukleotida u tri fragmenta gena BACH2, od kojih se dva nalaze u promotoru, a jedan u prvom intronu gena. Rezultati pokazuju statistički značajnu promjenu u CpG metilaciji gena BACH2 između pacijenata s upalnim bolestima crijeva i zdravih ljudi te ukazuje na potencijal ovoga gena kao metilacijskog biomarkera u perifernoj krvi.Crohn's disease and ulcerative colitis belong to a group of chronic diseases characterized by intestinal inflammation, with a common name of inflammatory bowel diseases. Ethiopatogenesis includes dysbiosis of the gut microbiota and impaired function of the immune system. The protein product of the BACH2 gene is a transcription factor with a significant role in development, activation and maturation of B lymphocytes, as well as regulation and senescence of T-lymphocytes and antibody production. Therefore, BACH2 has the key role in maintaining immune homeostasis. Genome-wide association studies revealed a connection between BACH2 and a number of autoimmune diseases, including inflammatory bowel disease. In this experiment, we analysed DNA methylation in BACH2 gene promoter isolated from blood samples of individuals suffering from CD and UC as well as healthy controls. For this purpose, methylation status was determined for each CpG dinucleotide in three BACH2 fragments using bisulfite pyrosequencing method. Two of the fragments are located in the gene promoter, and the third is in the first intron of the gene. The results show statistically significant change in the methylation pattern of BACH2 gene in patients with inflammatory bowel diseases compared to healthy individuals, thus revealing the potential of this gene as a methylation biomaker in peripheral blood

Immune evasion by proteolytic shedding of natural killer group 2, member D ligands in Helicobacter pylori infection

BackgroundHelicobacter pylori (H. pylori) uses various strategies that attenuate mucosal immunity to ensure its persistence in the stomach. We recently found evidence that H. pylori might modulate the natural killer group 2, member 2 (NKG2D) system. The NKG2D receptor and its ligands are a major activation system of natural killer and cytotoxic T cells, which are important for mucosal immunity and tumor immunosurveillance. The NKG2D system allows recognition and elimination of infected and transformed cells, however viruses and cancers often subvert its activation. Here we aimed to identify a potential evasion of the NKG2D system in H. pylori infection.MethodsWe analyzed expression of NKG2D system genes in gastric tissues of H. pylori gastritis and gastric cancer patients, and performed cell-culture based infection experiments using H. pylori isogenic mutants and epithelial and NK cell lines.ResultsIn biopsies of H. pylori gastritis patients, NKG2D receptor expression was reduced while NKG2D ligands accumulated in the lamina propria, suggesting NKG2D evasion. In vitro, H. pylori induced the transcription and proteolytic shedding of NKG2D ligands in stomach epithelial cells, and these effects were associated with specific H. pylori virulence factors. The H. pylori-driven release of soluble NKG2D ligands reduced the immunogenic visibility of infected cells and attenuated the cytotoxic activity of effector immune cells, specifically the anti-tumor activity of NK cells.ConclusionH. pylori manipulates the NKG2D system. This so far unrecognized strategy of immune evasion by H. pylori could potentially facilitate chronic bacterial persistence and might also promote stomach cancer development by allowing transformed cells to escape immune recognition and grow unimpeded to overt malignancy

Glycosylation of immunoglobulin G is regulated by a large network of genes pleiotropic with inflammatory diseases

Effector functions of immunoglobulin G (IgG) are regulated by the composition of a glycan moiety, thus affecting activity of the immune system. Aberrant glycosylation of IgG has been observed in many diseases, but little is understood about the underlying mechanisms. We performed a genome-wide association study of IgG N-glycosylation (N = 8090) and, using a data-driven network approach, suggested how associated loci form a functional network. We confirmed in vitro that knockdown of IKZF1 decreases the expression of fucosyltransferase FUT8, resulting in increased levels of fucosylated glycans, and suggest that RUNX1 and RUNX3, together with SMARCB1, regulate expression of glycosyltransferase MGAT3. We also show that variants affecting the expression of genes involved in the regulation of glycoenzymes colocalize with variants affecting risk for inflammatory diseases. This study provides new evidence that variation in key transcription factors coupled with regulatory variation in glycogenes modifies IgG glycosylation and has influence on inflammatory diseases

Jules Massenet: Pepeljuga (Simfonijski orkestar i solisti Muzičke akademije u Zagrebu, 8.5.2021.)

Snimka koncertne izvedbe održane na Muzičkoj akademiji u Koncertnoj dvorani "Blagoje Bersa" 8.5.2021. Izvođači: studenti solo pjevanja: Lucija Jelušić (sopran), Luka Šindija (tenor), Jurica Jurasić Kapun (bariton), Emilia Rukavina (mezzosopran), Gabriela Hrženjak (sopran), Patricia Žudetić (sopran), Tena Lončarević (mezzosopran), Matic Zakonjšek (tenor), Benjamin Šuran (bariton), Lobel Barun (bariton), Boris Beus (bas), Barbara Pijetlović, Marija Jurić, Vlatka Kladarić, Nela Katalenić Klinar, Martina Barišić, Dea Qivlaku (soprani i mezzosoprani); Simfonijski orkestar Muzičke akademije u Zagrebu; dirigentica: Dora Remenar. Program: Jules Massenet: Pepeljuga

Jules Massenet: Pepeljuga (Simfonijski orkestar i solisti Muzičke akademije u Zagrebu, 8.5.2021.)

Snimka koncertne izvedbe održane na Muzičkoj akademiji u Koncertnoj dvorani "Blagoje Bersa" 8.5.2021. Izvođači: studenti solo pjevanja: Lucija Jelušić (sopran), Luka Šindija (tenor), Jurica Jurasić Kapun (bariton), Emilia Rukavina (mezzosopran), Gabriela Hrženjak (sopran), Patricia Žudetić (sopran), Tena Lončarević (mezzosopran), Matic Zakonjšek (tenor), Benjamin Šuran (bariton), Lobel Barun (bariton), Boris Beus (bas), Barbara Pijetlović, Marija Jurić, Vlatka Kladarić, Nela Katalenić Klinar, Martina Barišić, Dea Qivlaku (soprani i mezzosoprani); Simfonijski orkestar Muzičke akademije u Zagrebu; dirigentica: Dora Remenar. Program: Jules Massenet: Pepeljuga

Proceedings Of The 23Rd Paediatric Rheumatology European Society Congress: Part Two

PubMe