Cellular adaptive mechanisms emerging after exposure to low levels of toxic agents or stressful stimuli comprise an important biological feature that has gained considerable scientific interest. Investigations of low-dose exposures to diverse chemical compounds signify the non-linear mode of action in the exposed cell or organism at such dose levels in contrast to the classic detrimental effects induced at higher ones, a phenomenon usually referred to as hormesis. The resulting phenotype is a beneficial effect that tests our physiology within the limits of our homeostatic adaptations. Therefore, doses below the region of adverse responses are of particular interest and are specified as the hormetic gain zone. The manifestation of redox adaptations aiming to prevent from disturbances of redox homeostasis represent an area of particular interest in hormetic responses, observed after exposure not only to stressors but also to compounds of natural origin, such as phytochemicals. Findings from previous studies on several agents demonstrate the heterogeneity of the specific zone in terms of the molecular events occurring. Major factors deeply involved in these biphasic phenomena are the bioactive compound per se, the dose level, the duration of exposure, the cell, tissue or even organ exposed to and, of course, the biomarker examined. In the end, the molecular fate is a complex toxicological event, based on beneficial and detrimental effects, which, however, are poorly understood to date.

Primary effusion lymphoma (PEL) is an unusual, human herpes virus-8 (HHV-8)–associated type of lymphoma, presenting as lymphomatous effusion in body cavities, without a detectable tumor mass. It primarily affects human immunodeficiency virus (HIV)-infected patients, but has also been described in other immunocompromised individuals. Although PEL is a B-cell lymphoma, the neoplastic cells are usually of the ‘null’ phenotype by immunocytochemistry. This report describes a case of PEL with T-cell phenotype in a HIV-negative patient and reviews all the relevant cases published until now. Our patient suffered from cirrhosis associated with Hepatitis B virus (HBV) infection and presented with a large ascitic effusion, in the absence of peripheral lymphadenopathy or solid mass within either the abdomen or the thorax. Paracentesis disclosed large lymphoma cells with anaplastic features consisting of moderate cytoplasm and single or occasionally multiple irregular nuclei with single or multiple prominent nucleoli. Immunocytochemically, these cells were negative for both CD3 and CD20, but showed a positive reaction for T-cell markers CD43 and CD45RO (VCHL-1). Furthermore, the neoplastic cells revealed strong positivity for EMA and CD30, but they lacked expression of ALK-1, TIA-1, and Perforin. The immune status for both HHV-8 and Epstein-Barr virus (EBV) was evaluated and showed positive immunostaining only for the former. The combination of the immunohistochemistry results with the existence of a clonal rearrangement in the immunoglobulin heavy chain gene (identified by PCR), were compatible with the diagnosis of PEL. The presence of T-cell markers was consistent with the diagnosis of PEL with an aberrant T-cell phenotype.

Wine and by-products of the winemaking process, such as grape stems, are rich in bioactive polyphenolic compounds that might be beneficial for animal and human health. In recent years, the administration of dietary polyphenols with strong antioxidant and cytoprotective properties has constituted an emerging line of research interest toward disease prevention. However, in scientific literature, only a limited number of studies have investigated the safety and the toxicological risks of polyphenolic compounds in vivo. Based on the above, the purpose of the present study was two-fold: first, to examine the effects of oral administration of a grape stem extract, derived from the Greek red wine Mavrodaphne, on mice redox biomarkers; and second, to investigate the biological effects of oral administration of a wine extract, derived from the emblematic Greek red wine Xinomavro, on rats. Toward this purpose, body weight, growth rate, hematological, biochemical, and histopathological parameters, as well as a panel of redox biomarkers, were examined. According to our results, the administration of Mavrodaphne grape stem extract in mice induced alterations in redox homeostasis, preventing mice from the adverse effects of lipid peroxidation. Contrariwise, the administration of Xinomavro wine extract induced both beneficial and harmful outcomes on rat redox status determined by the examined tissue. Collectively, our study reports that the Mavrodaphne grape stem extract, a serious pollutant when disposed in environmental matrices, is an important source of bioactive polyphenolic compounds that could protect from oxidative damage and improve animal and human health. Finally, the Xinomavro wine extract exerts tissue-specific changes in redox balance, which are indicative of the complexity that characterizes the biological systems.

Malignant peripheral nerve sheath tumor (MPNST) is an uncommon mesenchymal neoplasm showing nerve sheath differentiation, usually arising in large nerves of the trunk and extremities. Primary location in the parotid gland is rare. We describe fine needle aspiration (FNA) findings in a case of MPNST in the parotid gland. Differential diagnostic problems encountered in interpretation are discussed. A 39-year-old man underwent FNA of a well-circumscribed, painless, mobile mass of the parotid gland. Smears were cellular, with clusters of tightly packed spindle or oval cells arranged in a storiform or whorled pattern, showing clearly malignant features. Elongated nuclei with tapered ends and many angulated nuclei were encountered. The background contained abundant necrotic material with dispersed malignant nuclei. Neoplastic cells were positive for vimentin and weakly positive for S-100 and negative for cytokeratins 8 and 18 and HMB-45. Cytologic diagnosis was positive for malignant cells consistent with a spindle cell sarcoma, with morphologic features compatible to neural differentiation, confirmed by histologic examination. This case illustrates that attention to moiphologic criteria suggestive of nerve sheath phenotype supported by immunocytochemical data is extremely helpful and reliable in the diagnostic approach to MPNSTs, even in rare locations.

Perinatal exposure to environmental toxicants, even at regulatory relevant doses, can disrupt molecular programming during critical developmental windows, with long-term consequences for organ function and disease risk. We investigated sex-specific hepatic microRNA (miRNA) responses in Wistar rats following perinatal exposure to glyphosate at European Union (EU) acceptable daily intake (ADI) dose (0.5 mg/kg bw/day), at no-observed-adverse-effect level (NOAEL; 50 mg/kg bw/day), and mixed with 2,4-D (0.3 mg/kg bw/day) and dicamba (0.02 mg/kg bw/day), each at their ADI. Using small RNA sequencing, we identified distinct miRNA expression profiles in males and females, with the mixture inducing the most pronounced divergence (52 differentially expressed miRNAs between males and females). Functional enrichment analysis of validated miRNA targets revealed activation of apoptotic, oncogenic, and stress-related pathways in males, alongside downregulation of homeostatic and anti-fibrotic regulators. Females showed suppression of miRNAs involved in hormone signaling, development, and tissue regeneration, suggesting endocrine and adaptive disruption. Our findings highlight the importance of determining effects based on sex and sensitive developmental stages in toxicological assessment, since different regulatory programs may be involved in the response of males and females to xenobiotics. The identified miRNAs may represent early biomarkers of hepatic dysfunction following early-life herbicide exposure, supporting their utility in future risk evaluations.