Interplay between ubiquitin networks and NF-KB signaling

NF-kB transcription factors were discovered 25 years ago and since then they have been in the focus of biomedical research. Their important role in immune system development is recognized and NF-kB is becoming more attractive because of its role in cancer biology. Understanding the molecular mechanisms controlling NF-kB activity appear important as possible therapeutic targets of numerous human diseases. Here we summarize how ubiquitin networks control the NF-kB pathway and specifically focus on recent findings implicating linear ubiquitin chains as critical components in this process

Interplay between ubiquitin networks and NF-KB signaling

NF-kB transcription factors were discovered 25 years ago and since then they have been in the focus of biomedical research. Their important role in immune system development is recognized and NF-kB is becoming more attractive because of its role in cancer biology. Understanding the molecular mechanisms controlling NF-kB activity appear important as possible therapeutic targets of numerous human diseases. Here we summarize how ubiquitin networks control the NF-kB pathway and specifically focus on recent findings implicating linear ubiquitin chains as critical components in this process

Seme i proizvodi iz organske proizvodnje Instituta za ratarstvo i povrtarstvo

Formiranjem Odeljenja za organsku proizvodnju i biodiverzitet, Institut za ratarstvo i povrtarstvo iz Novog Sada je prihvatio izazov organske proizvodnje, kako u naučno-istraživačkom tako i u komercijalnom smislu. Institut od 2009. godine raspolaže certifikovanom organskom površinom, a od 2012. godine proširuje ove površine, odnosno uključuje druge parcele u proces certifikacije, sa ciljem stvaranja uslova za naučno-istraživački rad (organsko oplemenjivanje i druga istraživanja) i za proizvodnju certifikovanog organskog semena i sadnog materijala za domaće tržište i izvoz. Na navedenim povšinama naučno-istraživački rad se ostvaruje kroz projekte i oplemenjivačke programe ratarskih, povrtarskih i lekovitih vrsta. Institut proizvodi certifikovano organsko seme i sadni materijal sledećih ratarskih, povrtarskih i lekovitih biljnih vrsta: ozima pšenica spelta (Nirvana), ozima pšenica (Etida), soja (Galina), heljda (Novosadska), jesenji beli luk (Bosut), pasulj (Balkan), proso (Biserka), pitoma nana (Danica), bosiljak (Sitnolisni), neven (Gelb orange), mirođija (Domaća aromatična), kao i proizvode takođe iz certifikovane organske proizvodnje: herba i list pitome nane, etarska ulja i čajni koncentrati

The impact of IL-6 and IL-28B gene polymorphisms on treatment outcome of chronic hepatitis C infection among intravenous drug users in Croatia

Background Several genes and their single nucleotide polymorphisms (SNPs) are associated with either spontaneous resolution of hepatitis C infection or better treatment-induced viral clearance. We tested a cohort of intravenous drug users (IVDU) diagnosed with chronic hepatitis C virus (HCV) for treatment response and its association with the SNPs in the interleukin-6 (rs1800795-IL6) and the interleukin-28B (rs12979860-IL28B) genes. Methods The study included 110 Croatian IVDU positive for anti-HCV antibody. Genotyping was performed by polymerase chain reaction (PCR) based approach. Patients were treated by standard pegylated-interferon/ribavirin and followed throughout a period of four years, during which sustained virological response (SVR) was determined. All data were analysed with statistical package SPSS 19.0 (IBM Corp, Armonk, NY, USA) and PLINK v1.07 software. Results Patients showed a significantly better response to treatment according to the number of copies of the C allele carried at rs1800795-IL6 (P = 0.034). All but one of the patients with CC genotype achieved SVR (93%), whereas the response rate of patients with GG genotype was 64%. The association of rs1800795-IL6 with SVR status remained significant after further adjustment for patients’ age, fibrosis staging, and viral genotype (OR 2.15, 95% CI 1.16–4.68, P = 0.019). Distributions of allele frequencies at the locus rs12979860-IL28B among the study cohort and the underlying general population were suggestive of a protective effect of CC genotype in acquiring chronic hepatitis C in the Croatian IVDU population. Discussion The rs1800795-IL6 polymorphism is associated with positive response to treatment in IVDU patients positive for HCV infection. A protective role of rs12979860-IL28B CC genotype in acquiring chronic hepatitis C is suggested for Croatian IVDU population

Activation of cGAS-STING Pathway Is Associated with MSI-H Stage IV Colorectal Cancer

Colorectal cancer is the second most common cause of cancer-related mortality in adults. Understanding colorectal tumorigenesis at both the cellular and molecular levels is crucial for developing effective treatment options. Forty-one biopsy samples from patients with metastatic CRC (mCRC) were collected at Split University Hospital in Croatia. A total of 41 patients (21 with microsatellite unstable tumours and 20 with microsatellite stable tumours) were randomly included in the study. Immunolabelling of cGAS and STING in metastatic CRC was performed and further complemented by histological classification, tumour grade, and KRAS, NRAS, and BRAF mutational status of mCRC. In bivariate analysis, elevated expression of cGAS and STING was positively associated with MSI-H colon cancer (Fisher’s exact test, both p = 0.0203). Combined expression analysis of cGAS and STING showed a significantly higher percentage of patients with mCRC MSI-H with a fully or partially activated cGAS-STING signalling pathway (chi-square test, p = 0.0050). After adjusting for age, sex, and STING expression, increased cGAS expression remained significantly associated with MSI-H colon cancer in a multiple logistic regression model (β = 1.588, SE = ±0.799, p = 0.047). The cGAS-STING signalling axis represents a compelling new target for optimization of immune checkpoint inhibitor therapeutic approaches in patients with MSI-H stage IV CRC