Current medicinal chemistry
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Review
Functional Neuroimaging Biomarkers in Migraine: Diagnostic, Prognostic and Therapeutic Implications.
In current migraine clinical practice, conventional neuroimaging examinations are often sought to exclude possible causes of secondary headaches or migraineassociated disorders. Contrariwise, although advanced Magnetic Resonance Imaging (MRI) has improved tremendously our understanding of human brain processes in migraine patients, to the state of the art they have not superseded the conventional neuroimaging techniques in the migraine clinical setting. ⋯ The identification of diagnostic, prognostic and therapeutic advanced neuroimaging biomarkers in the migraine clinical setting, in order to approach to patients in a more and more rational and "tailored" way, is extremely intriguing and futuristic. Unfortunately, reliable and robust neuroimaging biomarkers are still lacking for migraine, probably due to both not completely understood pathogenesis and clinical and neuroimaging heterogeneity. Although further longitudinal advanced neuroimaging studies, aimed to identify effective neuroimaging biomarkers, are needed, this review aims to collect the main and most recent works on this topic.
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Gut microbiota, the largest symbiont community hosted in human organism, is emerging as a pivotal player in the relationship between dietary habits and health. Oral and, especially, intestinal microbes metabolize dietary components, affecting human health by producing harmful or beneficial metabolites, which are involved in the incidence and progression of several intestinal related and non-related diseases. Habitual diet (Western, Agrarian and Mediterranean omnivore diets, vegetarian, vegan and gluten-free diets) drives the composition of the gut microbiota and metabolome. ⋯ Specific relationships between diet and microbes, microbes and metabolites, microbes and immune functions and microbes and/or their metabolites and some human diseases are being established. Dietary treatments with fibers are the most effective to benefit the metabolome profile, by improving the synthesis of short chain fatty acids and decreasing the level of molecules, such as p-cresyl sulfate, indoxyl sulfate and trimethylamine N-oxide, involved in disease state. Based on the axis diet-microbiota-health, this review aims at describing the most recent knowledge oriented towards a profitable use of diet to provide benefits to human health, both directly and indirectly, through the activity of gut microbiota.
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Chemokines, which have chemotactic abilities, are comprised of a family of small cytokines with 8-10 kilodaltons. Chemokines work in immune cells by trafficking and regulating cell proliferation, migration, activation, differentiation, and homing. CXCR-4 is an alpha-chemokine receptor specific for stromal-derived-factor-1 (SDF-1, also known as CXCL12), which has been found to be expressed in more than 23 different types of cancers. ⋯ CXCL12/CXCR4 antagonists have been produced, which have shown encouraging results in anti-cancer activity. Here, we provide a brief overview of the CXCL12/CXCR4 axis as a molecular target for cancer treatment. We also review the potential utility of targeting CXCL12/CXCR4 axis in combination of immunotherapy and/or chemotherapy based on up-to-date literature and ongoing research progress.
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The human gut is a composite anaerobic environment with a large, diverse and dynamic enteric microbiota, represented by more than 100 trillion microorganisms, including at least 1000 distinct species. The discovery that a different microbial composition can influence behavior and cognition, and in turn the nervous system can indirectly influence enteric microbiota composition, has significantly contributed to establish the well-accepted concept of gut-brain axis. This hypothesis is supported by several evidence showing mutual mechanisms, which involve the vague nerve, the immune system, the hypothalamic-pituitaryadrenal (HPA) axis modulation and the bacteria-derived metabolites. ⋯ A possible correlation has been shown between these lipids and gut microbiota through different mechanisms. Indeed, systemic administration of specific bacteria can reduce abdominal pain through the involvement of cannabinoid receptor 1 in the rat; on the other hand, PEA reduces inflammation markers in a murine model of inflammatory bowel disease (IBD), and butyrate, producted by gut microbiota, is effective in reducing inflammation and pain in irritable bowel syndrome and IBD animal models. In this review, we underline the relationship among inflammation, pain, microbiota and the different lipids, focusing on a possible involvement of NAEs and SCFAs in the gut-brain axis and their role in the central nervous system diseases.
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Although survival of patients with different types of cancer has improved, cardiotoxicity induced by anti-neoplastic drugs remains a critical issue. Cardiac dysfunction after treatment with anthracyclines has historically been a major problem. However, also targeted therapies and biological molecules can induce reversible and irreversible cardiac dysfunction. ⋯ Moreover, PD-1 and PD-L1 can be expressed in rodent and human cardiomyocytes. During the last years several cases of fatal heart failure have been documented in melanoma patients treated with checkpoint inhibitors. The recent experience with cardiovascular toxic effects associated with checkpoint inhibitors introduces important concepts biologically and clinically relevant for future oncology trials and clinical practice.