Multiple Sclerosis: From the Application of Oligoclonal Bands to Novel Potential Biomarkers.

Multiple sclerosis is a chronic immune-mediated disorder of the central nervous system with a high heterogeneity among patients. In the clinical setting, one of the main challenges is a proper and early diagnosis for the prediction of disease activity. Current diagnosis is based on the integration of clinical, imaging, and laboratory results, with the latter based on the presence of intrathecal IgG oligoclonal bands in the cerebrospinal fluid whose detection via isoelectric focusing followed by immunoblotting represents the gold standard. Intrathecal synthesis can also be evidenced by the measurement of kappa free light chains in the cerebrospinal fluid, which has reached similar diagnostic accuracy compared to that of oligoclonal bands in the identification of patients with multiple sclerosis; moreover, recent studies have also highlighted its value for early disease activity prediction. This strategy has significant advantages as compared to using oligoclonal band detection, even though some issues remain open. Here, we discuss the current methods applied for cerebrospinal fluid analysis to achieve the most accurate diagnosis and for follow-up and prognosis evaluation. In addition, we describe new promising biomarkers, currently under investigation, that could contribute both to a better diagnosis of multiple sclerosis and to its monitoring of the therapeutic treatment response.

Does Gut-breast Microbiota Axis Orchestrates Cancer Progression?

Breast cancer, even today, can cause death. Therefore, prevention and early detection are fundamental factors. The mechanisms that favour it are genetic and epigenetic, and seem to play a significant role; also, the microbiota can change estrogen levels and can induce chronic inflammation in the neoplastic site, alternating the balance between proliferation and cell death. Activated steroid hormone receptors induce transcription of genes that encode for proteins involved in cell proliferation and activate another transduction pathway, inducing cell cycle progression and cell migration. These important studies have allowed to develop therapies with selective modulators of estrogen receptors (SERMs), able to block their proliferative and pro-tumorigenic action. Of fundamental importance is also the role played by the microbiota in regulating the metabolism of estrogens and their levels in the blood. There are microbial populations that are able to promote the development of breast cancer, through the production of enzymes responsible for the deconjugation of estrogens, the increase of these in the intestine, subsequent circulation and migration to other locations, such as the udder. Other microbial populations are, instead, able to synthesize estrogen compounds or mimic estrogenic action, and interfere with the metabolism of drugs, affecting the outcome of therapies. The microbial composition of the intestine and hormonal metabolism depend largely on eating habits; the consumption of fats and proteins favours the increase of estrogen in the blood, unlike a diet rich in fiber. Therefore, in-depth knowledge of the microbiota present in the intestine-breast axis could, in the future, encourage the development of new diagnostic and therapeutic approaches to breast cancers.