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showing 10 items of 5003 documents
Strategies against nonsense: oxadiazoles as translational readthrough-inducing drugs (TRIDs)
2019
This review focuses on the use of oxadiazoles as translational readthrough-inducing drugs (TRIDs) to rescue the functional full-length protein expression in mendelian genetic diseases caused by nonsense mutations. These mutations in specific genes generate premature termination codons (PTCs) responsible for the translation of truncated proteins. After a brief introduction on nonsense mutations and their pathological effects, the features of various classes of TRIDs will be described discussing differences or similarities in their mechanisms of action. Strategies to correct the PTCs will be presented, particularly focusing on a new class of Ataluren-like oxadiazole derivatives in comparison …
Non-coding RNAs Functioning in Colorectal Cancer Stem Cells
2016
In recent years, the hypothesis of the presence of tumor-initiating cancer stem cells (CSCs) has received a considerable support. This model suggested the existence of CSCs which, thanks to their self-renewal properties, are able to drive the expansion and the maintenance of malignant cell populations with invasive and metastatic potential in cancer. Increasing evidence showed the ability of such cells to acquire self-renewal, multipotency, angiogenic potential, immune evasion, symmetrical and asymmetrical divisions which, along with the presence of several DNA repair mechanisms, further enhance their oncogenic potential making them highly resistant to common anticancer treatments. The main…
A Two-Component regulatory system with opposite effects on glycopeptide antibiotic biosynthesis and resistance
2020
AbstractThe glycopeptide A40926, produced by the actinomycete Nonomuraea gerenzanensis, is the precursor of dalbavancin, a second-generation glycopeptide antibiotic approved for clinical use in the USA and Europe in 2014 and 2015, respectively. The final product of the biosynthetic pathway is an O-acetylated form of A40926 (acA40926). Glycopeptide biosynthesis in N. gerenzanensis is dependent upon the dbv gene cluster that encodes, in addition to the two essential positive regulators Dbv3 and Dbv4, the putative members of a two-component signal transduction system, specifically the response regulator Dbv6 and the sensor kinase Dbv22. The aim of this work was to assign a role to these two ge…
Estrogenic activity of zearalenone, α-zearalenol and β-zearalenol assessed using the E-Screen assay in MCF-7 cells
2017
Mycotoxins, including zearalenone (ZEA), can occur worldwide in cereals. They can enter the food chain and cause several health disorders. ZEA and its derivatives (α-zearalenol, α-ZOL and β-zearalenol, β-ZOL) have structural analogy to estrogen, thus they can bind to estrogen receptors (ERs). In order to characterize the estrogenic activity of ZEA, α-ZOL and β-ZOL, the proliferation of ER-positive human breast cancer cells (MCF-7) exposed to these mycotoxins was measured. After exposure at levels ranging from 6.25 to 25 µM, cell proliferation was evaluated by using the E-Screen bioassay. In accordance with previous studies, our results show the estrogenic activity of ZEA, α-ZOL and β-ZOL in…
Burden of Disease in PWH Harboring a Multidrug-Resistant Virus: Data from the PRESTIGIO Registry
2020
AbstractBackgroundCurrently, no data are available on the burden of morbidity and mortality in people with HIV-1 (PWH) harboring a 4-class drug-resistant (4DR) virus (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase strand transfer inhibitors). The study aimed to assess the incidence of clinical events and death in this population.MethodsThis was a cohort study on PWH from the PRESTIGIO Registry with a documented 4DR virus. Burden of disease was defined as the occurrence of any new event including an AIDS-defining event (ADE) or non-AIDS-defining event (NADE) or death from any cause after 4DR evidence (baseline). Co…
Adherence to dietary treatment and clinical factors associated with anti-transglutaminase antibodies in celiac disease during the follow-up
2021
Introduction In clinical practice, celiac disease (CD) is monitored through anti-transglutaminase (TGA-IgA) antibody levels. The normalization of serum levels in successive periodic measurements indicates good response and adherence to dietary treatment. Objectives To evaluate the factors associated with the evolution of TGA-IgA antibodies and their association with dietary non-compliance and diseases related to CD. Methods This prospective observational study was carried out in 254 participants, who were recruited from patients from a hospital in southern Spain. Information about sex, age, serological test results, HLA DQ2/DQ8 haplotypes, mucosal atrophy, gastrointestinal and extra-intesti…
Adjuvant MUC vaccination with tecemotide after resection of colorectal liver metastases: a randomized, double-blind, placebo-controlled, multicenter …
2020
ABSTRACT Resection of colorectal liver metastases (CRLM) is a potential curative treatment for patients with metastatic colorectal cancer (mCRC) with liver-limited disease (LLD). Although long-term survival improved considerably within the last decades, high recurrence rates of 50-75% after resection remain a major challenge.Tecemotide (L-BLP25) is an antigen-specific cancer vaccine inducing immunity against mucin-1 (MUC1). The LICC trial aimed to improve survival in patients with mCRC after R0/R1 resection of CRLM. LICC was a binational, randomized, double-blind, placebo-controlled, multicenter phase 2 study including patients with R0/R1 resected CRLM without evidence of metastatic disease…
Longevity and risk factors of post restorations after up to 15 years: A practice-based study.
2020
Abstract Introduction The aims of this multicenter, practice-based cohort study were to evaluate the success and survival of endodontically treated teeth with post restorations (ETT+Ps) and to analyze factors associated with the longevity of ETT+Ps. Methods Eight general dental practitioners each placed up to 27 ETT+Ps without any restriction to post materials or dimensions. Only incisors, canines, and premolars were included. At the last follow-up visit, ETT+Ps were considered as successful if the post and the initially placed definitive restoration were sufficient, whereas ETT+Ps were considered as survived if the post was still in function. Multilevel Cox proportional hazards models were…
Decreased Fibrogenesis After Treatment with Pirfenidone in a Newly Developed Mouse Model of Intestinal Fibrosis
2016
BACKGROUND Fibrosis as a common problem in patients with Crohn's disease is a result of an imbalance toward excessive tissue repair. At present, there is no specific treatment option. Pirfenidone is approved for the treatment of idiopathic pulmonary fibrosis with both antifibrotic and anti-inflammatory effects. We subsequently investigated the impact of pirfenidone treatment on development of fibrosis in a new mouse model of intestinal fibrosis. METHODS Small bowel resections from donor mice were transplanted subcutaneously into the neck of recipients. Animals received either pirfenidone (100 mg/kg, three times daily, orally) or vehicle. RESULTS After administration of pirfenidone, a signif…
Resveratrol Interferes with IL1-β-Induced Pro-Inflammatory Paracrine Interaction between Primary Chondrocytes and Macrophages
2016
International audience; State of the art. Osteoarthritis (OA) is a chronic articular disease characterized by cartilage degradation and osteophyte formation. OA physiopathology is multifactorial and involves mechanical and hereditary factors. So far, there is neither preventive medicine to delay cartilage breakdown nor curative treatment. Objectives. To investigate pro-inflammatory paracrine interactions between human primary chondrocytes and macrophages following interleukin-1-β (IL-1β) treatment; to evaluate the molecular mechanism responsible for the inhibitory effect of resveratrol. Results. The activation of NF-κB in chondrocytes by IL-1β induced IL-6 secretion. The latter will then ac…