The gut–brain axis (GBA) refers to the biochemical bidirectional communication between the central nervous system (CNS) and the gastrointestinal tract, linking brain and gut functions. It comprises a complex network of interactions involving the endocrine, immune, autonomic, and enteric nervous systems. The balance of this bidirectional pathway depends on the composition of the gut microbiome and its metabolites. While the causes of neurodegenerative diseases (NDDs) vary, the gut microbiome plays a crucial role in their development and prognosis. NDDs are often associated with an inflammation-related gut microbiome. However, restoring balance to the gut microbiome and reducing inflammation may have therapeutic benefits. In particular, introducing short-chain fatty acid-producing bacteria, key metabolites that support gut homeostasis, can help counteract the inflammatory microbiome. This strong pathological link between the gut and NDDs underscores the gut–brain axis (GBA) as a promising target for therapeutic intervention. This review, by scrutinizing the more recent original research articles published in PubMed (MEDLINE) database, emphasizes the emerging notion that GBA is an equally important pathological marker for neurological movement disorders, particularly in Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s disease and neurotraumatic disorders such as traumatic brain injury and spinal cord injury. Additionally, the GBA presents a promising therapeutic target for managing these diseases.

Glioblastoma (GB) is a tumor of the central nervous system characterized by high proliferation and invasiveness. The standard treatment for GB includes radiotherapy and chemotherapy; however, new therapies are needed. Particular attention was given to the role of histone methyltransferase enhancer of zeste-homolog-2 (EZH2) in GB. Recently, several EZH2-inhibitors have been developed, particularly GSK343 is well-known to regulate apoptosis and autophagy processes; however, its abilities to modulate canonical/non-canonical NF-κB/IκBα pathways or an immune response in GB have not yet been investigated. Therefore, this study investigated for the first time the effect of GSK343 on canonical/non-canonical NF-κB/IκBα pathways and the immune response, by an in vitro, in vivo and ex vivo model of GB. In vitro results demonstrated that GSK343 treatments 1, 10 and 25 μM significantly reduced GB cell viability, showing the modulation of canonical/non-canonical NF-κB/IκBα pathway activation. In vivo GSK343 reduced subcutaneous tumor mass, regulating canonical/non-canonical NF-κB/IκBα pathway activation and the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). Ex vivo results confirmed the anti-proliferative effect of GSK343 and also demonstrated its ability to regulate immune response through CXCL9, CXCL10 and CXCL11 expression in GB. Thus, GSK343 could represent a therapeutic strategy to counteract GB progression, thanks to its ability to modulate canonical/non-canonical NF-κB/IκBα pathways and immune response.

New therapeutic approaches are needed to improve the outcome of patients with glioblastoma (GBM). Propionate, a short-chain fatty acid (SCFA), has a potent antiproliferative effect on various tumor cell types. Peroxisome proliferator-activated receptor (PPAR) ligands possess anticancer properties. We aimed to investigate the PPAR-γ/SCFAs interaction in in vitro and in vivo models of GBM. The U87 cell line was used in the in vitro study and was treated with sodium propionate (SP). U87 cells were silenced by using PPAR-γ siRNA or Ctr siRNA. In the in vivo study, BALB/c nude mice were inoculated in the right flank with 3 × 10⁶ U-87 cells. SP (doses of 30 and 100 mg/kg) and GW9662 (1 mg/kg) were administered. In vitro exposure of GBM to SP resulted in prominent apoptosis activation while the autophagy pathway was promoted by SP treatments by influencing autophagy-related proteins. Knockdown of PPAR-γ sensitized GBM cells and blocked the SP effect. In vivo, SP was able to decrease tumor growth and to resolve GBM tissue features. SP promoted apoptosis and autophagy pathways and tumor cell proliferation leading to cell cycle arrest through a PPAR-γ-dependent mechanism suggesting that the PPAR-γ/SCFAs axis could be targeted for the management of GBM.

Glioblastoma is the most commonly malignant and aggressive brain tumor, with a high mortality rate. The role of the purine nucleotide adenosine and its interaction with its four subtypes receptors coupled to the different G proteins, A1, A2A, A2B, and A3, and its different physiological functions in different systems and organs, depending on the active receptor subtype, has been studied for years. Recently, several works have defined extracellular adenosine as a tumoral protector because of its accumulation in the tumor microenvironment. Its presence is due to both the interaction with the A2A receptor subtype and the increase in CD39 and CD73 gene expression induced by the hypoxic state. This fact has fueled preclinical and clinical research into the development of efficacious molecules acting on the adenosine pathway and blocking its accumulation. Given the success of anti-cancer immunotherapy, the new strategy is to develop selective A2A receptor antagonists that could competitively inhibit binding to its endogenous ligand, making them reliable candidates for the therapeutic management of brain tumors. Here, we focused on the efficacy of adenosine receptor antagonists and their enhancement in anti-cancer immunotherapy.

Over the last three years, humanity has been facing one of the most serious health emergencies due to the global spread of Coronavirus disease (COVID-19). In this scenario, the research of reliable biomarkers of mortality from COVID-19 represents a primary objective. Pentraxin 3 (PTX3), a highly conserved protein of innate immunity, seems to be associated with a worse outcome of the disease. Based on the above, this systematic review and meta-analysis evaluated the prognostic potential of PTX3 in COVID-19 disease. We included 12 clinical studies evaluating PTX3 in COVID-19 patients. From our research, we found increased PTX3 levels compared to healthy subjects, and notably, PTX3 was even more augmented in severe COVID-19 rather than non-severe cases. Moreover, we performed a meta-analysis to establish if there were differences between ICU and non-ICU COVID-19 patients in PTX3-related death. We combined 5 studies for a total of 543 ICU vs. 515 non-ICU patients. We found high significative PTX3-related death in ICU COVID-19 hospitalized individuals (184 out of 543) compared to non-ICU (37 out of 515), with an overall effect OR: 11.30 [2.00, 63.73]; p = 0.006. In conclusion, we probed PTX3 as a reliable marker of poor outcomes after COVID-19 infection as well as a predictor of hospitalized patients’ stratification.

Inflammatory bowel diseases (IBDs) involving Crohn’s disease (CD) and ulcerative colitis (UC) are gastrointestinal (GI) disorders in which abdominal pain, discomfort, and diarrhea are the major symptoms. The immune system plays an important role in the pathogenesis of IBD and, as indicated by several clinical studies, both innate and adaptative immune response has the faculty to induce gut inflammation in UC patients. An inappropriate mucosal immune response to normal intestinal constituents is a main feature of UC, thus leading to an imbalance in local pro- and anti-inflammatory species. Ulva pertusa, a marine green alga, is known for its important biological properties, which could represent a source of beneficial effects in various human pathologies. We have already demonstrated the anti-inflammatory, antioxidant, and antiapoptotic effects of an Ulva pertusa extract in a murine model of colitis. In this study, we aimed to examine thoroughly Ulva pertusa immunomodulatory and pain-relieving properties. Colitis was induced by using the DNBS model (4 mg in 100 μL of 50% ethanol), whereas Ulva pertusa was administered daily at the dosage of 50 and 100 mg/kg by oral gavage. Ulva pertusa treatments have been shown to relieve abdominal pain while modulating innate and adaptative immune-inflammatory responses. This powerful immunomodulatory activity was specifically linked with TLR4 and NLRP3 inflammasome modulation. In conclusion, our data suggest Ulva pertusa as a valid approach to counteract immune dysregulation and abdominal discomfort in IBD.