The role of carbonic anhydrase XII (CAXII) in the chemoresistance of glioblastoma is unexplored. We found CAXII and P-glycoprotein (Pgp) coexpressed in neurospheres derived from 3 of 3 patients with different genetic backgrounds and low response to temozolomide (time to recurrence: 6–9 months). CAXII was necessary for the Pgp efflux of temozolomide and second-line chemotherapeutic drugs, determining chemoresistance in neurospheres. Psammaplin C, a potent inhibitor of CAXII, resensitized primary neurospheres to temozolomide by reducing temozolomide efflux via Pgp. This effect was independent of other known temozolomide resistance factors present in the patients. The overall survival in orthotopic patient-derived xenografts of temozolomide-resistant neurospheres, codosed with Psammaplin C and temozolomide, was significantly increased over temozolomide-treated (P < 0.05) and untreated animals (P < 0.02), without detectable signs of systemic toxicity. We propose that a CAXII inhibitor in combination with temozolomide may provide a new and effective approach to reverse chemoresistance in glioblastoma stem cells. This novel mechanism of action, via the interaction of CAXII and Pgp, ultimately blocks the efflux function of Pgp to improve glioblastoma patient outcomes.

Glioblastoma (GBM) stem cells (GSCs), responsible for tumor growth, recurrence, and resistance to therapies, are considered the real therapeutic target, if they had no molecular mechanisms of resistance, in comparison with the mass of more differentiated cells which are insensitive to therapies just because of being differentiated and nonproliferating. GSCs occur in tumor niches where both stemness status and angiogenesis are conditioned by the microenvironment. In both perivascular and perinecrotic niches, hypoxia plays a fundamental role. Fifteen glioblastomas have been studied by immunohistochemistry and immunofluorescence for stemness and differentiation antigens. It has been found that circumscribed necroses develop inside hyperproliferating areas that are characterized by high expression of stemness antigens. Necrosis developed inside them because of the imbalance between the proliferation of tumor cells and endothelial cells; it reduces the number of GSCs to a thin ring around the former hyperproliferating area. The perinecrotic GSCs are nothing else that the survivors remnants of those populating hyperproliferating areas. In the tumor, GSCs coincide with malignant areas so that the need to detect where they are located is not so urgent.

The role of the microbiota in health and disease has long been recognized and, so far, the cutaneous microbiota in humans has been widely investigated. The research regarded mainly the microbiota variations between body districts and disease skin states (i.e., atopic dermatitis, psoriasis, acne). In fact, relatively little information is available about the composition of the healthy skin microbiota. The cosmetic industry is especially interested in developing products that maintain and/or improve a healthy skin microbiota. Therefore, in the present work, the authors chose to investigate in detail the structure and composition of the basal bacterial community of the face. Ninety-six cheek samples (48 women and 48 men) were collected in the same season and the same location in central northern Italy. Bacterial DNA was extracted, the 16S rDNA gene was amplified by PCR, the obtained amplicons were subjected to next generation sequencing. The principal members of the community were identified at the genus level, and statistical analyses showed significant variations between the two sexes. This study identified abundant members of the facial skin microbiota that were rarely reported before in the literature and demonstrated the differences between male and female microbiota in terms of both community structure and composition.

Formation of neurospheres (NS) in cultures of glioblastomas (GBMs), with self-renewal, clonogenic capacities, and tumorigenicity following transplantation into immunodeficient mice, may denounce the existence of brain tumor stem cells (BTSCs) in vivo. In sixteen cell lines from resected primary glioblastomas, NS showed the same genetic alterations as primary tumors and the expression of stemness antigens. Adherent cells (AC), after adding 10% of fetal bovine serum (FBS) to the culture, were genetically different from NS and prevailingly expressed differentiation antigens. NS developed from a highly malignant tumor phenotype with proliferation, circumscribed necrosis, and high vessel density. Beside originating from transformed neural stem cells (NSCs), BTSCs may be contained within or correspond to dedifferentiated cells after mutation accumulation, which reacquire the expression of stemness antigens.

Gut dysbiosis refers to an imbalance in gut microbiota composition and function. Opuntia ficus-indica extract has been shown to modulate gut microbiota by improving SCFA production in vivo and gastrointestinal discomfort (GD) in humans. The aim of this study was to demonstrate the efficacy of Odilia^TM on gastrointestinal health by changing the microbial diversity of species involved in inflammation, immunity, oxidation, and the brain–gut–muscle axis. A randomized, double-blind clinical trial was conducted in 80 adults with gut dysbiosis. The intervention consisted of a 300 mg daily intake of Odilia^TM (n = 40) or maltodextrin as a placebo (n = 40), administered for 8 weeks. Intervention effect was evaluated using 16S metagenomics and GIQLI/GSAS scores at baseline, at 4 and 8 weeks. Eight weeks of Odilia^TM supplementation positively modulates gut microbiota composition with a significant reduction in the Firmicutes to Bacteroidetes ratio (p = 0.0012). Relative abundances of beneficial bacteria (Bacteroides and Clostridium_XIVa) were significantly increased (p < 0.001), in contrast to a significant reduction in pro-inflammatory bacteria (p < 0.001). Accordingly, GIQLI and GSAS scores revealed successful improvement in GD. Odilia^TM may represent an effective and well-tolerated treatment in subjects with gut dysbiosis.