Aphyllophorales del Bosco della Mesola (Ferrara)

Abstract

Aphyllophorales from Mesola Forest (Ferrara) Italy—The present check-list is the first contribution to the knowledge of Aphyllophorales growing in the area of the Mesola Forest. The paper deals with 72 species of Aphyllophorales collected during the years 1980-1983. A further contribution will complete the picture of the Aphyllophorales flora which is particularly interesting and abundant in the forest.

Some of the species listed in the present paper are quite interesting since they are uncommon: Meruliopsis hirtellus and Oxyporus latemarginatus are new to Italy; Flaviporus semisupiniformis is the first European finding and the second world collection.     

Comparative Cardiac Toxicity of Anthracyclines In Vitro and In Vivo in the Mouse

Purpose

The antineoplastic efficacy of anthracyclines is limited by their cardiac toxicity. In this study, we evaluated the toxicity of doxorubicin, non-pegylated liposomal-delivered doxorubicin, and epirubicin in HL-1 adult cardiomyocytes in culture as well as in the mouse in vivo.

Methods

The cardiomyocytes were incubated with the three anthracyclines (1 µM) to assess reactive oxygen generation, DNA damage and apoptotic cell death. CF-1 mice (10/group) received doxorubicin, epirubicin or non-pegylated liposomal-doxorubicin (10 mg/kg) and cardiac function was monitored by Doppler echocardiography to measure left ventricular ejection fraction (LVEF), heart rate (HR) and cardiac output (CO) both prior to and 10 days after drug treatment.

Results

In HL-1 cells, non-pegylated liposomal-doxorubicin generated significantly less reactive oxygen species (ROS), as well as less DNA damage and apoptosis activation when compared with doxorubicin and epirubicin. Cultured breast tumor cells showed similar sensitivity to the three anthracyclines. In the healthy mouse, non-pegylated liposomal doxorubicin showed a minimal and non-significant decrease in LVEF with no change in HR or CO, compared to doxorubicin and epirubicin.

Conclusion

This study provides evidence for reduced cardiac toxicity of non-pegylated-liposomal doxorubicin characterized by attenuation of ROS generation, DNA damage and apoptosis in comparison to epirubicin and doxorubicin.     

Pharmacological targeting of the ephrin receptor kinase signalling by GLPG1790 in vitro and in vivo reverts oncophenotype,induces myogenic differentiation and radiosensitizes embryonal rhabdomyosarcoma cells

Background

EPH (erythropoietin-producing hepatocellular) receptors are clinically relevant targets in several malignancies. This report describes the effects of GLPG1790, a new potent pan-EPH inhibitor, in human embryonal rhabdomyosarcoma (ERMS) cell lines.

Methods

EPH-A2 and Ephrin-A1 mRNA expression was quantified by real-time PCR in 14 ERMS tumour samples and in normal skeletal muscle (NSM). GLPG1790 effects were tested in RD and TE671 cell lines, two in vitro models of ERMS, by performing flow cytometry analysis, Western blotting and immunofluorescence experiments. RNA interfering experiments were performed to assess the role of specific EPH receptors. Radiations were delivered using an x-6 MV photon linear accelerator. GLPG1790 (30 mg/kg) in vivo activity alone or in combination with irradiation (2 Gy) was determined in murine xenografts.

Results

Our study showed, for the first time, a significant upregulation of EPH-A2 receptor and Ephrin-A1 ligand in ERMS primary biopsies in comparison to NSM. GLPG1790 in vitro induced G1-growth arrest as demonstrated by Rb, Cyclin A and Cyclin B1 decrease, as well as by p21 and p27 increment. GLPG1790 reduced migratory capacity and clonogenic potential of ERMS cells, prevented rhabdosphere formation and downregulated CD133, CXCR4 and Nanog stem cell markers. Drug treatment committed ERMS cells towards skeletal muscle differentiation by inducing a myogenic-like phenotype and increasing MYOD1, Myogenin and MyHC levels. Furthermore, GLPG1790 significantly radiosensitized ERMS cells by impairing the DNA double-strand break repair pathway. Silencing of both EPH-A2 and EPH-B2, two receptors preferentially targeted by GLPG1790, closely matched the effects of the EPH pharmacological inhibition. GLPG1790 and radiation combined treatments reduced tumour mass by 83% in mouse TE671 xenografts.

Conclusions

Taken together, our data suggest that altered EPH signalling plays a key role in ERMS development and that its pharmacological inhibition might represent a potential therapeutic strategy to impair stemness and to rescue myogenic program in ERMS cells.

     

The role of physical cues in the regulation of host recognition and acceptance behavior ofAphidius ervi Haliday (Hymenoptera: Braconidae)

The role of color and shape in the host recognition and acceptance behavior ofAphidius ervi Haliday was studied. A quantitative analysis of the oviposition behavior ofA. ervi was carried out with a computer-aided analysis of 150 video-recorded oviposition sequences on its natural host,Acyrthosiphon pisum (Harris). The importance of visual stimuli was assessed in a choice condition bioassay, observing the behavioral reaction of female parasitoids to various test materials flame-sealed into glass capillaries. Glass beads 2 and 6 mm in diameter and a flat arena were coated with cornicle secretion ofA. pisum, and their acceptance rates by both naive and experienced female parasitoids were assessed under no-choice conditions. In most cases,A. ervi females switched from random searching to attack position when the host was within a range of 1 cm, suggesting that host recognition is regulated in part by cues acting before physical contact. The glass capillary bioassay indicated that visual cues are important factors in the host recognition and acceptance phases. Pea aphid color alone can elicit the oviposition response of naiveA. ervi females, and this response is enhanced when color is combined with aphid shape. The cornicle secretion ofA. pisum stimulated an oviposition response which was stronger in naive females ofA. ervi than in experienced ones and was not significantly affected by the glass bead size or flat surface. These results, along with those from previous studies, suggest that manipulation of the oviposition behavior ofA. ervi is feasible under laboratory conditions.     

Skewing effect of sulprostone on dendritic cell maturation compared with dinoprostone

Background

Dendritic cells (DCs) are the most efficient antigen-presenting cells and act at the center of the immune system owing to their ability to control both immune tolerance and immunity. In cancer immunotherapy, DCs play a key role in the regulation of the immune response against tumors and can be generated ex vivo with different cytokine cocktails. Methods. We evaluated the feasibility of dinoprostone (PGE₂) replacement with the molecular analog sulprostone, in our good manufacturing practice (GMP) protocol for the generation of DC-based cancer vaccine. We characterized the phenotype and the function of DCs matured in the presence of sulprostone as a potential substitute of dinoprostone in the pro-inflammatory maturation cocktail consisting of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β) and IL-6. Results. We found that sulprostone invariably reduces the recovery, but does not significantly modify the viability and the purity of DCs. The presence of sulprostone in the maturation cocktail increases the adhesion of single cells and of clusters of DCs to the flask, making them more similar to their immature counterpart in terms of adhesion and spreading proprieties. Moreover, we observed that sulprostone impairs the expression of co-stimulatory molecules and the spontaneous as well as the directed migration capacity of DCs.

Selective Vulnerability of Spinal and Cortical Motor Neuron Subpopulations in delta7 SMA Mice

Loss of the survival motor neuron gene (SMN1) is responsible for spinal muscular atrophy (SMA), the most common inherited cause of infant mortality. Even though the SMA phenotype is traditionally considered as related to spinal motor neuron loss, it remains debated whether the specific targeting of motor neurons could represent the best therapeutic option for the disease. We here investigated, using stereological quantification methods, the spinal cord and cerebral motor cortex of ∆7 SMA mice during development, to verify extent and selectivity of motor neuron loss. We found progressive post-natal loss of spinal motor neurons, already at pre-symptomatic stages, and a higher vulnerability of motor neurons innervating proximal and axial muscles. Larger motor neurons decreased in the course of disease, either for selective loss or specific developmental impairment. We also found a selective reduction of layer V pyramidal neurons associated with layer V gliosis in the cerebral motor cortex. Our data indicate that in the ∆7 SMA model SMN loss is critical for the spinal cord, particularly for specific motor neuron pools. Neuronal loss, however, is not selective for lower motor neurons. These data further suggest that SMA pathogenesis is likely more complex than previously anticipated. The better knowledge of SMA models might be instrumental in shaping better therapeutic options for affected patients.     

Laparoscopic conservative management of ureteral endometriosis: a survey of eighty patients submitted to ureterolysis

Background  

this study aims to evaluate the effectiveness and safety of laparoscopic conservative management of ureteral endometriosis.     

Unfolding studies of tissue transglutaminase

Activation of tissue transglutaminase by calcium involves a conformational change which allows exposition of the active site to the substrate via movements of domains 3 and 4 that lead to an increase of the inter-domain distance. The inhibitor GTP counteracts these changes. Here we investigate the possible existence of non-native conformational states still compatible with the enzyme activity produced by chemical and thermal perturbations. The results indicate that chemical denaturation is reversible at low guanidine concentrations but irreversible at high concentrations of guanidine. Indeed, at low guanidine concentrations tissue TG-ase exists in a non-native state which is still affected by the ligands as in the native form. In contrast, thermal unfolding is always irreversible, with aggregation and protein self-crosslinkage in the presence of calcium. DSC thermograms of the native protein in the absence of ligands consist of two partly overlapped transitions, which weaken in the presence of calcium and merge together and strengthen in the presence of GTP. Overall, the present work shows, for the first time, the reversible denaturation of a TG-ase isoenzyme and suggests the possibility that also in in vivo, the enzyme may acquire non-native conformations relevant to its patho-physiological functions.     

Wasting syndrome with deep bradycardia as presenting manifestation of long-standing severe male hypogonadotropic hypogonadism: a case series

Background

Non-thyroidal illness (NTI) refers to changes in thyroid hormone levels in critically ill patients in the absence of primary hypothalamic-pituitary-thyroid dysfunction, and these abnormalities usually resolve after clinical recovery. However, NTI can be accompanied by primary thyroid dysfunction. We report herein a case of a woman with NTI accompanied by primary hyperthyroidism.

Case presentation

A 52-year-old female was admitted to the intensive care unit with heart failure and atrial fibrillation. She had a longstanding thyroid nodule, and a thyroid function test revealed low levels of triiodothyronine and free thyroxine as well as undetectable thyroid stimulating hormone (TSH). She was diagnosed with NTI, and her TSH level began to recover but not completely at discharge. The thyroid function test was repeated after 42 months to reveal primary hyperthyroidism, and a thyroid scan confirmed a toxic nodule.

Conclusion

This case suggests that although NTI was diagnosed, primary hyperthyroidism should be considered as another possible diagnosis if TSH is undetectable. Thyroid function tests should be repeated after clinical recovery from acute illness.     

Potential of fecal microbiota for early-stage detection of colorectal cancer

Several bacterial species have been implicated in the development of colorectal carcinoma (CRC), but CRC-associated changes of fecal microbiota and their potential for cancer screening remain to be explored. Here, we used metagenomic sequencing of fecal samples to identify taxonomic markers that distinguished CRC patients from tumor-free controls in a study population of 156 participants. Accuracy of metagenomic CRC detection was similar to the standard fecal occult blood test (FOBT) and when both approaches were combined, sensitivity improved > 45% relative to the FOBT, while maintaining its specificity. Accuracy of metagenomic CRC detection did not differ significantly between early- and late-stage cancer and could be validated in independent patient and control populations (N = 335) from different countries. CRC-associated changes in the fecal microbiome at least partially reflected microbial community composition at the tumor itself, indicating that observed gene pool differences may reveal tumor-related host–microbe interactions. Indeed, we deduced a metabolic shift from fiber degradation in controls to utilization of host carbohydrates and amino acids in CRC patients, accompanied by an increase of lipopolysaccharide metabolism.