A growing number of studies is focusing on the pharmacology and feasibility of bioactive compounds as a novel valuable approach to target a variety of human diseases related to neurological degeneration. Among the group of the so-called medicinal mushrooms (MMs), Hericium erinaceus has become one of the most promising candidates. In fact, some of the bioactive compounds extracted from H. erinaceus have been shown to recover, or at least ameliorate, a wide range of pathological brain conditions such as Alzheimer’s disease, depression, Parkinson’s disease, and spinal cord injury. In a large body of in vitro and in vivo preclinical studies on the central nervous system (CNS), the effects of erinacines have been correlated with a significant increase in the production of neurotrophic factors. Despite the promising outcome of preclinical investigations, only a limited number of clinical trials have been carried out so far in different neurological conditions. In this survey, we summarized the current state of knowledge on H. erinaceus dietary supplementation and its therapeutic potential in clinical settings. The bulk collected evidence underlies the urgent need to carry out further/wider clinical trials to prove the safety and efficacy of H. erinaceus supplementation, offering significant neuroprotective applications in brain pathologies.

Frailty during aging is an increasing problem associated with locomotor and cognitive decline, implicated in poor quality of life and adverse health consequences. Considering the microbiome–gut–brain axis, we investigated, in a longitudinal study, whether and how physiological aging affects gut microbiome composition in wild-type male mice, and if and how cognitive frailty is related to gut microbiome composition. To assess these points, we monitored mice during aging at five selected experimental time points, from adulthood to senescence. At all selected experimental times, we monitored cognitive performance using novel object recognition and emergence tests and measured the corresponding Cognitive Frailty Index. Parallelly, murine fecal samples were collected and analyzed to determine the respective alpha and beta diversities, as well as the relative abundance of different bacterial taxa. We demonstrated that physiological aging significantly affected the overall gut microbiome composition, as well as the relative abundance of specific bacterial taxa, including Deferribacterota, Akkermansia, Muribaculaceae, Alistipes, and Clostridia VadinBB60. We also revealed that 218 amplicon sequence variants were significantly associated to the Cognitive Frailty Index. We speculated that some of them may guide the microbiome toward maladaptive and dysbiotic conditions, while others may compensate with changes toward adaptive and eubiotic conditions.

Glioblastoma (GBM) is the most malignant form of primary brain tumor. It is characterized by the presence of highly invasive cancer cells infiltrating the brain by hijacking neuronal mechanisms and interacting with non-neuronal cell types, such as astrocytes and endothelial cells. To enter the interstitial space of the brain parenchyma, GBM cells significantly shrink their volume and extend the invadopodia and lamellipodia by modulating their membrane conductance repertoire. However, the changes in the compartment-specific ionic dynamics involved in this process are still not fully understood. Here, using noninvasive perforated patch-clamp and live imaging approaches on various GBM cell lines during a wound-healing assay, we demonstrate that the sodium-calcium exchanger (NCX) is highly expressed in the lamellipodia compartment, is functionally active during GBM cell migration, and correlates with the overexpression of large conductance K+ channel (BK) potassium channels. Furthermore, a NCX blockade impairs lamellipodia formation and maintenance, as well as GBM cell migration. In conclusion, the functional expression of the NCX in the lamellipodia of GBM cells at the migrating front is a conditio sine qua non for the invasion strategy of these malignant cells and thus represents a potential target for brain tumor treatment.

Breast cancer (BC) is the second most common cause of brain metastasis onset in patients, with the cerebellum accounting for the 33% of cases. In the current study, using a 4T1 triple-negative mouse BC model, we revealed that an orally administered medicinal mushrooms (MM) blend, rich in β-glucans, played a direct and specific anti-cancer action on cerebellar metastases, also bettering locomotor performances. The neuroprotective effect of the MM blend plays through (i) a direct and specific inhibition of cerebellar metastatization pattern typical of TNBC (with an induced reduction of about 50% of metastases density) and (ii) the regulation of apoptosis and proliferation-related genes, as suggested by expression changes of specific molecular markers, i.e. PCNA, p53, Bcl2, BAX, CASP9, CASP3, Hsp70 and AIF. Therefore, inhibiting the metastatization process, triggering a significant apoptosis increase, and lessening cell proliferation, this MM supplement, employed as adjuvant treatment in association with conventional therapy, could represent a promising approach, in the field of Integrative Oncology, for patients' management in both prevention and treatment of brain metastases from BC.

This study presents the first comprehensive proteomic profile of an Italian strain of Schizophyllum commune, a highly heterogeneous white-rot fungal species with significant potential for industrial, nutraceutical, cosmeceutical, and clinical applications. Three protein extraction methods and their impact on yield and resulting protein composition have been compared. Results revealed that the combination of Tris–Cl and urea increases the total protein yield and the variety of enzymatic species related to pivotal pathways. Notably, over 2000 proteins were identified, including enzymes involved in the growth and development of mycelium, trehalose biosynthesis, and different types of carbohydrate-active enzymes (CAZymes). These enzymes are crucial for nutraceutical and agro-industrial applications of S. commune. The multiple-step proteomic approach used could be a model for investigating other fungal species.

Pleurotus nebrodensis, a rare endemic Sicilian mushroom with notable gastronomic and medicinal value, attracts interest for its potential antioxidant properties, though data on its biological effects in skin models are lacking. This study evaluated the antioxidant activities of several aqueous extracts from wild (1a, 2a, 3a, 1b, 2b, and 3b) and cultivated (CAN1 °F, 3A, 2B(II), and CAN2 °F) P. nebrodensis basidiomes in human keratinocytes (HaCaT cells). Extracts were characterized through DPPH radical scavenging assay, MTT viability assay, and intracellular ROS and mitochondrial SOX quantification by DCFH-DA and MitoSOX Red fluorescence analyses. The methodology specifically included two approaches in keratinocytes: co-treatment of extracts and H₂O₂ to investigate direct scavenger activity, and pre-treatment to assess the preventive activity on oxidative stress modulation. This analysis demonstrated that selected extracts (1b and CAN2 °F) exert a dual action, combining anti-intracellular ROS and anti-mitochondrial SOX preventive effect with a direct free radical scavenging activity in human keratinocytes. In particular, CAN2 °F exerts its activity predominantly through prevention (modulation of cellular defenses), while 1b primarily functions as a direct intracellular ROS and mitochondrial SOX scavenger. Notably, glucan quantification revealed a correlation between β-glucan content and the overall antioxidant activity. These findings provide the first evidence of P. nebrodensis’s anti-ROS and anti-SOX efficacy in human keratinocytes, highlighting its potential as a source of natural bioactives for cosmeceutical and dermatological applications.