Further Evidence on the Role of Thyroid Autoimmunity in Women with Recurrent Miscarriage

It has been twenty years since the first paper reporting the association between thyroid antibodies (TAIs) and spontaneous miscarriage was published. Following this observation, several studies have clearly demonstrated an increased prevalence of TAI in patients with recurrent miscarriage (RM). However, the exact mechanism underlying this association remains a matter of debate. The aim of the present study was to evaluate the thyroid function, throughout a specific test, in patient with RM and TAI focusing on the hypothesis that TAI should be an indirect sign of a mild thyroid dysfunction. 46 patients with RM and TAI were included in the study. All patients underwent short TRH stimulation test showing an abnormal response in the vast majority of cases (65%). Normal FT4 and FT3 mean values were found whereas TSH values were in the upper normal range (2.64 ± 1.3 mUI/L). Our data support the hypothesis that in patients with RM the presence of TAI is an indirect sign of a subtle thyroid dysfunction detectable by a specific test. This test give the possibility to identify women with RM in which specific therapeutic approaches could effectively improve the possibility for a successful pregnancy

Evolution of clinical trials in ovarian cancer management over the past 20 years: never settle down, always go beyond

Purpose. A practice synthesis of available evidence-based medicine data in ovarian cancer (OC), aiming to provide directions for future research. Materials and Methods. We performed a systematic review. PubMed was searched for relevant OC trials between January 2000 and December 2019. Results. Out of 865 references screened, 199 trials were found eligible for inclusion. Most trials were multicenter (83.9%). There was a trend reduction in the number of patients enrolled/per study over the years. Studies testing targeted/biological therapies dominated the second decade (60 trials in 2010-2019 versus 2 trials in 2000-2009). The proportion of trials with positive survival and clinical outcomes significantly increased from 23.8% in early 2000s to 54.1% in the last 5 years. Trials with histology/molecular biomarker criteria were more likely to meet progression-free survival endpoint than those without these selection criteria (69.2% versus 32.6%). Conclusion. This systematic review suggests a trend of increased positive studies, mainly linked to precision medicine

Immunolocalization of Nesfatin-1 in the Gastrointestinal Tract of the Common Bottlenose Dolphin Tursiops truncatus

First identified as an anorexigenic peptide, in the last decades, several studies have suggested that Nesfatin-1 (Nesf-1) is a pleiotropic hormone implicated in numerous regulatory processes in peripheral organs and tissues. In vertebrates, Nesf-1 is indeed expressed in the central nervous system and peripheral organs. In this study, we characterized the pattern of Nesf-1 distribution within the digestive tract of the common bottlenose dolphin (Tursiops truncatus), composed of three gastric chambers and and intestine without a clear subdivision in the small and large intestine, also lacking a caecum. Our results indicated that Nesf-1 is widely distributed in cells of the mucosal epithelium of the gastric chambers. Most of the immunoreactivity was observed in the second chamber, compared to the first and third chambers. Immunopositivity was also found in nerve fibers and neurons, scattered or/and clustered in ganglion structures along all the esaminaned gastrointestinal tracts. These observations add new data on the highly conserved role of Nesf-1 in the mammalian digestive system

Tissue- and Cell Type-Specific Expression of the Long Noncoding RNA Klhl14-AS in Mouse

lncRNAs are acquiring increasing relevance as regulators in a wide spectrum of biological processes. The extreme heterogeneity in the mechanisms of action of these molecules, however, makes them very difficult to study, especially regarding their molecular function. A novel lncRNA has been recently identified as the most enriched transcript in mouse developing thyroid. Due to its genomic localization antisense to the protein-encoding Klhl14 gene, we named it Klhl14-AS. In this paper, we highlight that mouse Klhl14-AS produces at least five splicing variants, some of which have not been previously described. Klhl14-AS is expressed with a peculiar pattern, characterized by diverse relative abundance of its isoforms in different mouse tissues. We examine the whole expression level of Klhl14-AS in a panel of adult mouse tissues, showing that it is expressed in the thyroid, lung, kidney, testis, ovary, brain, and spleen, although at different levels. In situ hybridization analysis reveals that, in the context of each organ, Klhl14-AS shows a cell type-specific expression. Interestingly, databases report a similar expression profile for human Klhl14-AS. Our observations suggest that this lncRNA could play cell type-specific roles in several organs and pave the way for functional characterization of this gene in appropriate biological contexts

"Stockpile" of slight transcriptomic changes determines the indirect genotoxicity of low-dose BPA in thyroid cells

Epidemiological and experimental data highlighted the thyroid-disrupting activity of bisphenol A (BPA). Although pivotal to identify the mechanisms of toxicity, direct low-dose BPA effects on thyrocytes have not been assessed. Here, we report the results of microarray experiments revealing that the transcriptome reacts dynamically to low-dose BPA exposure, adapting the changes in gene expression to the exposure duration. The response involves many genes, enriching specific pathways and biological functions mainly cell death/proliferation or DNA repair. Their expression is only slightly altered but, since they enrich specific pathways, this results in major effects as shown here for transcripts involved in the DNA repair pathway. Indeed, even though no phenotypic changes are induced by the treatment, we show that the exposure to BPA impairs the cell response to further stressors. We experimentally verify that prolonged exposure to low doses of BPA results in a delayed response to UV-C-induced DNA damage, due to impairment of p21-Tp53 axis, with the BPA-treated cells more prone to cell death and DNA damage accumulation. The present findings shed light on a possible mechanism by which BPA, not able to directly cause genetic damage at environmental dose, may exert an indirect genotoxic activity

In vivo role of different domains and of phosphorylation in the transcription factor Nkx2-1

Background: The transcription factor Nkx2-1 (also known as TTF-1, Titf1 or T/EBP) contains two apparently redundant activation domains and is post-translationally modified by phosphorylation. We have generated mouse mutant strains to assess the roles of the two activation domains and of phosphorylation in mouse development and differentiation. Results: Mouse strains expressing variants of the transcription factor Nkx2-1 deleted of either activation domain have been constructed. Phenotypic analysis shows for each mutant a distinct set of defects demonstrating that distinct portions of the protein endow diverse developmental functions of Nkx2-1. Furthermore, a mouse strain expressing a Nkx2-1 protein mutated in the phosphorylation sites shows a thyroid gland with deranged follicular organization and gene expression profile demonstrating the functional role of phosphorylation in Nkx2-1. Conclusions: The pleiotropic functions of Nkx2-1 are not all due to the protein as a whole since some of them can be assigned to separate domains of the protein or to specific post-translational modifications. These results have implication for the evolutionary role of mutations in transcription factors. © 2011 Silberschmidt et al; licensee BioMed Central Ltd

A Morphological and Ultrastructural Study of the Anterior Digestive Tract of Adult Nile Tilapia Oreochromis niloticus

Among the most-used fish species in aquaculture is the Nile tilapia, due to its rapid growth rate and its adaptation to a wide range of farming conditions. A careful description of the morphology of the digestive tract, particularly the esophagus and stomach, allows a better understanding of the relationship between structure and function. Combining scanning and light microscopy we highlighted the presence of five different zones in the stomach (1: esophagus-gastric lumen passage; 2: descending glandular portion; 3: fundic portion; 4: ascending glandular portion; 5: gastric-pyloric transition portion). Histochemical investigation showed a secretion of carboxylates mucopolysaccharides along the esophagus and sulphated complex carbohydrates in the stomach. These results suggest that mucins play a protective role of the epithelial lining, which is essential for a correct digestive process. Finally, the characterization of the main cellular structures may be inspiring for more advanced studies aiming to decipher the role of specific molecules, such as neuropeptides, involved in the physiological digestive process

Immunohistochemical identification of resistin in the uterus of ewes subjected to different diets: Preliminary results

Resistin is a polypeptide hormone of the adipokine-family, primarily, but not exclusively, produced by the adipose tissue. Recent studies suggested that resistin may affect the male and female reproductive activity. The study aim was to immunohistochemically evaluate the presence and distribution of resistin in the ovine uterus. Uterine samples were collected from two groups of ewes at the end of an experimental trial during which the animals of the first group (CTRL) were fed only by grazing while those of the second one (EXP) were supplemented with barley and corn. Using a monoclonal antibody against resistin, tested by Western Blot, the immunopositive reaction was identified in the cytoplasm of epithelial lining cells and uterine glands. The endogenous production of resistin seemed to be affected by different diet, as evidenced by staining differences between the CTRL and EXP groups. Our findings support the existence of a peripheral resistin system in the sheep uterus. It is possible that this system is involved in the functionality of the uterus, which is also affected by the animal’s nutritional status.