Different cortical excitability profiles in hereditary brain iron and copper accumulation.

BACKGROUND AND AIM: Neurodegeneration with brain iron accumulation (NBIA) and Wilson's disease (WD) is considered the prototype of neurodegenerative disorders characterised by the overloading of iron and copper in the central nervous system. Growing evidence has unveiled the involvement of these metals in brain cortical neurotransmission. Aim of this study was to assess cortical excitability profile due to copper and iron overload. METHODS: Three patients affected by NBIA, namely two patients with a recessive hereditary parkinsonism (PARK9) and one patient with aceruloplasminemia and 7 patients with neurological WD underwent transcranial magnetic stimulation (TMS) protocols to assess cortical excitability. Specifically, we evaluated the motor thresholds that reflect membrane excitability related to the voltage-gated sodium channels in the neurons of the motor system and the ease of activation of motor cortex via glutamatergic networks, and ad hoc TMS protocols to probe inhibitory-GABAergic (short interval intracortical inhibition, SICI; short-latency afferent inhibition, SAI; cortical silent period, CSP) and excitatory intracortical circuitry (intracortical facilitation, ICF). RESULTS: Patients with NBIA exhibited an abnormal prolongation of CSP respect to HC and WD patients. On the contrary, neurological WD displayed higher motor thresholds and reduced CSP and SICI. CONCLUSION: Hereditary conditions due to overload of copper and iron exhibited peculiar cortical excitability profiles that can help during differential diagnosis between these conditions. Moreover, such results can give us more clues about the role of metals in acquired neurodegenerative disorders, such as Parkinson disease, Alzheimer disease, and multiple sclerosis.

HMGB1-TIM3-HO1: A New Pathway of Inflammation in Skin of SARS-CoV-2 Patients? A Retrospective Pilot Study.

The SARS-CoV-2 pandemic has completely disrupted the health systems of the entire planet. From the earliest months, it became increasingly clear that in addition to affecting the upper airways and lungs, there were other organs that could be affected. Among these, the skin became a real "sentinel signal" to be able to even suspect COVID-19. Background: this study deals with a little-explored issue for now: the study of skin immunopathology in SARS-CoV-2 positive subjects ascertained using the most reliable methods available. Methods: we used skin biopsy samples from SARS-CoV-2 positive and negative patients, studying morphology (Hematoxylin-Eosin), T lymphocyte population (CD4 and CD8), three markers such as HMGB-1, TIM-3 and HO-1 by immunohistochemistry. Results: although the presence of the CD4 and CD8 T population did not differ statistically significantly, we found greater activation and release of HMGB-1 in skin samples from SARS-CoV-2 positive patients, greater immunolabeling for TIM-3 at the level of CD4 and CD8 and a reduced expression of Heme oxygenase 1. Conclusions: these results support the possibility that there is immune deregulation in SARS-CoV-2 positive patients who develop skin manifestations of various kinds.

Formalin-Fixed and Paraffin-Embedded Samples for Next Generation Sequencing: Problems and Solutions.

Over the years, increasing information has been asked of the pathologist: we have moved from a purely morphological diagnosis to biomolecular and genetic studies, which have made it possible to implement the use of molecular targeted therapies, such as anti-epidermal growth factor receptor (EGFR) molecules in EGFR-mutated lung cancer, for example. Today, next generation sequencing (NGS) has changed the approach to neoplasms, to the extent that, in a short time, it has gained a place of absolute importance and diagnostic, prognostic and therapeutic utility. In this scenario, formaldehyde-fixed and paraffin-embedded (FFPE) biological tissue samples are a source of clinical and molecular information. However, problems can arise in the genetic material (DNA and RNA) for use in NGS due to fixation, and work is being devoted to possible strategies to reduce its effects. In this paper, we discuss the applications of FFPE tissue samples in the execution of NGS, we focus on the problems arising with the use of this type of material for nucleic acid extraction and, finally, we consider the most useful strategies to prevent and reduce single nucleotide polymorphisms (SNV) and other fixation artifacts.

Primary Breast Extranodal Marginal Zone Lymphoma in Primary Sjögren Syndrome: Case Presentation and Relevant Literature.

The association between autoimmune diseases, mostly rheumatoid arthritis, systemic lupus erythematosus, celiac disease and Sjögren syndrome, and lymphoma, has been widely demonstrated by several epidemiologic studies. By a mechanism which has not yet been entirely elucidated, chronic activation/stimulation of the immune system, along with the administration of specific treatments, may lead to the onset of different types of lymphoma in such patients. Specifically, patients affected by Sjögren syndrome may develop lymphomas many years after the original diagnosis. Several epidemiologic, hematologic, and histological features may anticipate the progression from Sjögren syndrome into lymphoma but, to the best of our knowledge, a definite pathogenetic mechanism for such progression is still missing. In fact, while the association between Sjögren syndrome and non-Hodgkin lymphoma, mostly extranodal marginal zone lymphomas and, less often, diffuse large B-cell, is well established, many other variables, such as time of onset, gender predilection, sites of occurrence, subtype of lymphoma, and predictive factors, still remain unclear. We report on a rare case of primary breast lymphoma occurring three years after the diagnosis of Sjögren syndrome in a 57-year-old patient. The diagnostic work-up, including radiograms, core needle biopsy, and histological examination, is discussed, along with emerging data from the recent literature, thus highlighting the usefulness of breast surveillance in Sjögren syndrome patients.

Structural data and immunomodulatory properties of a water-soluble heteroglycan extracted from the mycelium of an Italian isolate of Ganoderma lucidum.

Mushrooms produce a wide range of bioactive polysaccharides, different from each other in chemical structure and biological effects. In the last years, the idea to develop functional foods or drugs containing fungal polysaccharides is attracting great attention. Fruiting bodies of Basidiomycetes Ganoderma lucidum are commonly used in Oriental medicine to treat several disorders. G. lucidum polysaccharides - mainly ß-glucans and heteroglycans - have numerous biological properties such as antitumour and immunomodulatory activities. This report shows, by gene expression analyses and bioenergetic assays, immunomodulatory properties and capacity to improve glucose metabolism of a water-soluble heteroglycan extracted from mycelium of an Italian isolate of G. lucidum. The findings suggest the use of the heteroglycan as probiotic or ingredient in functional foods, being easy to produce and disperse in a food matrix thanks to its water-solubility. Heteroglycan could exert protective effects in pro-inflammatory conditions and benefits for people characterised by suppressed immune response.

Fungistatic activity of Zanthoxylum rhoifolium Lam. bark extracts against fungal plant pathogens and investigation on mechanism of action in Botrytis cinerea.

Plant-derived compounds are emerging as an alternative choice to synthetic fungicides. Chloroform-methanol extract, obtained from the bark of Zanthoxylum rhoifolium, a member of Rutaceae, showed a fungistatic effect on Botrytis cinerea, Sclerotinia sclerotiorum, Alternaria alternata, Colletotrichum gloeosporioides and Clonostachys rosea, when added to the growth medium at different concentrations. A fraction obtained by gel separation and containing the alkaloid O-Methylcapaurine showed significant fungistatic effect against B. cinerea and S. sclerotiorum, two of the most destructive phytopathogenic fungi. The underlying mechanism of such an inhibition was further investigated in B. cinerea, a fungus highly prone to develop fungicide resistance, by analysing the expression levels of a set of genes (BcatrB, P450, CYP51 and TOR). O-Methylcapaurine inhibited the expression of all the analysed genes. In particular, the expression of BcatrB gene, encoding a membrane drug transporter involved in the resistance to a wide range of xenobiotic compounds, was strongly inhibited (91%).