Role of Na+/Ca2+ Exchanger (NCX) in Glioblastoma Cell Migration (In Vitro).

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.

Hericium erinaceus in Neurodegenerative Diseases: From Bench to Bedside and Beyond, How Far from the Shoreline?

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.

Fighting secondary triple-negative breast cancer in cerebellum: A powerful aid from a medicinal mushrooms blend.

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 ß-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.

The Many Ages of Microbiome-Gut-Brain Axis.

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.