LIF-Dependent Signaling: New Pieces in the Lego

LIF, a member of the IL6 family of cytokine, displays pleiotropic effects on various cell types and organs. Its critical role in stem cell models (e.g.: murine ES, human mesenchymal cells) and its essential non redundant function during the implantation process of embryos, in eutherian mammals, put this cytokine at the core of many studies aiming to understand its mechanisms of action, which could benefit to medical applications. In addition, its conservation upon evolution raised the challenging question concerning the function of LIF in species in which there is no implantation. We present the recent knowledge about the established and potential functions of LIF in different stem cell models, (embryonic, hematopoietic, mesenchymal, muscle, neural stem cells and iPSC). We will also discuss EVO-DEVO aspects of this multifaceted cytokine

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Extraintestinal Manifestations and Intestinal Complications in Patients with Crohn's Disease: Associations with Some Clinico-Laboratory Findings, Immunological Markers and Therapy

Crohn's disease (CD) may have some severe complications that pose an increasing health burden and negatively impact the quality of life. There are two major types - intestinal and extraintestinal complications, in which immune and non-immune mechanisms take place. We aimed to search for some associations between specific extraintestinal manifestation and intestinal complications in CD patients with some clinicallaboratory findings, immunological markers, and the therapy administered. We examined retrospectively medical files of 26 patients with CD at mean age 42 ± 13 years, including the laboratory results. The immunological markers fecal calprotectin (FC) and fecal lactoferrin (FL) were assessed in frozen fecal samples of the chosen patients. Seventy-three percent of the investigated CD patients had some extraintestinal manifestation and/or intestinal complications, at least 13/26 had intestinal complications. All three patients with extraintestinal signs were positive for FC and 2/3 were positive for FL. We observed a higher serum level of CRP (24.49 mg/l vs. 3.13 mg/l, p = 0.010), slightly lowered serum level of hemoglobin (120 g/l vs. 145 g/l, p = 0.044) and about 2-fold lower iron level (7.23 μmol/l vs. 14.0 μmol/l, p = 0.019) in patients with intestinal complications compared to patients without complications, respectively. Four out of thirteen patients with intestinal complications were without immunosuppressive therapy at the time of our study, and nine out of thirteen - on immunosuppressive drugs. Routine laboratory and immunology testing could be beneficial for gastroenterologists in identifying patients at high risk for the development of complications and in the decision making for more aggressive therapy early after diagnosis

Different pharynx closure techniques in laryngectomy as a risk for pharyngocutaneous fistula

Introduction: One of the most frequent and troublesome complication following laryngectomy is pharyngocutaneous fistula (PCF). There are a lot of different risk factors for PCF suspected and evaluated, but only few proven.Objective: Evaluation the role of different pharynx closure techniques on PCF-incidence.Material and method: The charts of 92 patients, treated for carcinoma of the larynx with laryngectomy at MBAL "Sv. Marina" between july 2007 and december 2014 (86 males, 6 females, aged 61.9 +/- 8.2 years; T4=39, T3=53; N0=71 and N+ =21) were evaluated retrospectively. Three types of closure of the neohypopharynx were used: linear plasty in 31 cases, Y-shaped plasty in 46 cases and atypical type of closure with local tissues being stretched beyond the midline in the remaining 6 cases (called ZZ, TL or L). The primary endpoint was development of clinically evident PCF. The analysis was performed via Student's t-test.Results: The overall incidence of PCF was 7.53%. 1/46 (2.17%) in the Y-plasty group, 3/31 (9.68%) in the I-plasty group and 1/6 (16.67%) in the atypical plasty group developed PCF. The statistical result of the analysis does not find significance in the development of PCF between the groups.Conclusion: The type of the suture line for closure of the neohypopharynx in previously unirradiated patients with otherwise uniform surgical technique does not appear to be a risk factor for PCF.Der Erstautor gibt keinen Interessenkonflikt an