Biochemical Signatures of Doppel Protein in Human Astrocytomas to Support Prediction in Tumor Malignancy

Doppel (Dpl) is a membrane-bound glycoprotein mainly expressed in the testis of adult healthy people. It is generally absent in the central nervous system, but its coding gene sequence is ectopically expressed in astrocytoma specimens and in derived cell lines. In this paper, we investigated the expression and the biochemical features of Dpl in a panel of 49 astrocytoma specimens of different WHO malignancy grades. As a result, Dpl was expressed in the majority of the investigated specimens (86%), also including low grade samples. Importantly, Dpl exhibited different cellular localizations and altered glycan moieties composition, depending on the tumor grade. Most low-grade astrocytomas (83%) showed a membrane-bound Dpl, like human healthy testis tissue, whereas the majority of high-grade astrocytomas (75%) displayed a cytosolic Dpl. Deglycosylation studies with N-glycosidase F and/or neuraminidase highlighted defective glycan moieties and an unexpected loss of sialic acid. To find associations between glial tumor progression and Dpl biochemical features, predictive bioinformatics approaches were produced. In particular, Decision tree and Nomogram analysis showed well-defined Dpl-based criteria that separately clustered low-and high-grade astrocytomas. Taken together, these findings show that in astrocytomas, Dpl undergoes different molecular processes that might constitute additional helpful tools to characterize the glial tumor progression

Line-field confocal optical coherence tomography: a new tool for non-invasive differential diagnosis of pustular skin disorders

Background The spectrum of pustular skin disorders (PSD) is large and particularly challenging, including inflammatory, infectious and amicrobial diseases. Moreover, although pustules represent the unifying clinical feature, they can be absent or not fully developed in the early stage of the disease. The line-field confocal optical coherence tomography (LC-OCT) is a recently developed imaging technique able to perform a non-invasive, in vivo, examination of the epidermis and upper dermis, reaching very high image resolution and virtual histology. Objectives We aimed to investigate the potentialities of LC-OCT in the non-invasive differential diagnosis of a series of 11 PSD with different aetiology, microscopic features, body location and incidence rates. Materials and Methods Complete LC-OCT imaging (i.e. 2D/3D frames, videos) was performed on a total of 19 patients (10 females and 9 males) aged between 35 and 79 years. Images were blindly evaluated and compared with corresponding histopathologic findings. Results The LC-OCT imaging was able to detect with high accuracy the pustule structure including shape, margins, morphology and cellular content, along with peculiar epidermal and adnexal alterations in each condition, including: Acute Generalized Exanthematous Pustulosis, Generalized pustular psoriasis, Generalized pustular figurate erythema, Subcorneal Pustular Dermatosis, Intraepidermal IgA pustulosis, Palmoplantar pustulosis, Palmoplantar pustular psoriasis. Herpetic whitlow, Acrodermatitis continua of Hallopeau, Vesicopustular Sweet syndrome and Vesicopustular Eosinophilic cellulitis, with pustular appearance, were also compared. Conclusions The new LC-OCT can represent a rapid, non-invasive and painless tool which can help differentiating among PSD of different aetiology and microscopic morphology in clinical mimickers in daily practice

Erythema nodosum associated with Staphylococcus xylosus septicemia.

Staphylococcus xylosus is a coagulase-negative staphylococcus. It is a commensal bacterium associated with skin and mucous membranes and occasionally it can cause human infections. We report the first case of erythema nodosum developed in a young woman with S. xylosus septicemia and specific serum antibody response

Low expression of Ki-67/MIB-1 labeling index in IDH wild type glioblastoma predicts prolonged survival independently by MGMT methylation status

PurposeThe Ki-67/MIB-1 labeling index (LI) is clinically used to differentiate between high and low-grade gliomas, while its prognostic value remains questionable. Glioblastoma (GBM) expressing wild-type isocitrate dehydrogenase IDHwt, a relatively common malignant brain tumor in adults, is characterized by a dismal prognosis. Herein, we have retrospectively investigated the prognostic role of Ki-67/MIB-1-LI in a large group of IDHwt GBM.MethodsOne hundred nineteen IDHwt GBM patients treated with surgery followed by Stupp's protocol in our Institution between January 2016 and December 2021 were selected. A cut-off value for Ki-67/MIB-1-LI was used with minimal p-value based approach.ResultsA multivariate analysis showed that Ki-67/MIB-1-LI expression < 15% significantly correlated with a longer overall survival (OS), independently from the age of the patients, Karnofsky performance status scale, extent of surgery and O-6-methylguanine (O6-MeG)-DNA methyltransferase promoter methylation status.ConclusionsAmong other studies focused on Ki-67/MIB-1-LI, this is the first observational study showing a positive correlation between OS of IDHwt GBM patients and Ki-67/MIB-1-LI that we propose as a new predictive marker in this subtype of GBM

Possible Implication of Local Immune Response in Darier's Disease: An Immunohistochemical Characterization of Lesional Inflammatory Infiltrate

Cell-mediated immunity is considered to be normal in Darier's Disease (DD), an inherited skin disorder complicated by skin infections. To date, there are no investigations on the local inflammatory infiltrate in DD skin lesions. In this immunohistochemical study we characterized and quantified it, making comparisons with two other inflammatory skin disorders, that is, pemphigus vulgaris (PV) and lichen ruber planus (LRP), and with the normal skin (NSk). We found a significant (P < .05) decrease of CD1a+ Langerhans cells (LCs) in DD, compared to PV, LRP, and NSk, and of CD123+ plasmacytoid dendritic cells (pDCs), compared to PV and LRP. We hypothesize that the genetic damage of keratinocytes might result in a loss of some subsets of dendritic cells and, consequently, in an impaired local immune response, which might worsen the infections that inevitably occur in this disease

AUTOCOUNTER, an ImageJ JavaScript to analyze LC3B-GFP expression dynamics in autophagy-induced astrocytoma cells

An ImageJ JavaScript, AUTOCOUNTER, was specifically developed to monitor and measure LC3B-GFP expression in living human astrocytoma cells, namely T98G and U373-MG. Discrete intracellular GFP fluorescent spots derived from transduction of a Baculovirus replication-defective vector (BacMam LC3B-GFP), followed by microscope examinations at different times. After viral transgene expression, autophagy was induced by Rapamycin administration and assayed in ph-p70S6K/p70S6K and LC3B immunoblotting expression as well as by electron microscopy examinations. A mutated transgene, defective in LC3B lipidation, was employed as a negative control to further exclude fluorescent dots derived from protein intracellular aggregation. The ImageJ JavaScript was then employed to evaluate and score the dynamics changes of the number and area of LC3B-GFP puncta per cell in time course assays and in complex microscope examinations. In conclusion, AUTOCOUNTER enabled to quantify LC3B-GFP expression and to monitor dynamics changes in number and shapes of autophagosomal-like vesicles: it might therefore represent a suitable algorithmic tool for in vitro autophagy modulation studies

A rare association of ganglioglioma and cavernous malformation: Report of two cases and literature review

Background: Some glial tumors have been observed in association with different types of vascular malformations of the brain (angiogliomas). However, the association of ganglioglioma with other vascular malformations is extremely rare, with only few cases reported in the literature, one of which is referred to as “angioganglioglioma.” Case Description: Two patients presented with acute onset of neurological symptoms, with magnetic resonance imaging (MRI) nding of cavernoma of the left middle cerebellar penduncle, and small mass of the chiasmatic region, respectively. After microsurgical excision, histopathological examination revealed mixed ganglioglioma and cavernous malformation in both cases. Postoperative course was uneventful, and follow‐up MRI showed complete removal of the tumor with no recurrence after 4 years. Conclusions: Angiogliomas are very uncommon tumors. In literature, we found different interpretations of such lesions, although they should most probably be considered as distinct pathological entities. Although the association of ganglioglioma with cavernoma is extremely rare, it could be considered as a most peculiar form of angioglioma, and supports the existence of angioganglioglioma