Current medicinal chemistry
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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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Asthma is a heterogeneous disease characterized by chronic airway inflammation that results in a wide spectrum of clinical manifestations. Patients with severe asthma represent a substantial share of consumption of healthcare resources and hospitalization. Moreover, these patients are at risk of increased morbidity and mortality. ⋯ The long-term safety of these biologics is a relevant issue that should be addressed. Unfortunately, little is known about non-type 2 asthma. Further studies are needed to identify biomarkers to guide targeted therapies of different forms of non-type 2 asthma.
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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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Ethanol is known to have both γ-Aminobutyric acid agonist and Nmethyl- D-aspartate antagonist characteristics similar to commonly used volatile anesthetic agents. Recent evidence demonstrates that autophagy can reduce the development of ethanol induced neurotoxicity. Recent studies have found that general anesthesia can cause longterm impairment of both mitochondrial morphogenesis and synaptic transmission in the developing rat brain, both of which are accompanied by enhanced autophagy activity. Autophagy may play an important role in general anesthetic mediated neurotoxicity. ⋯ Autophagy may play a role in the development of anesthetic related neurotoxicity. Understanding this may lead to strategies or therapies aimed at preventing or ameliorating general anesthetic agent mediated neurotoxicity.
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Chronic pain states are clinically relevant and yet unsolved conditions impacting on quality of life and representing an important social and economic burden; these diseases are poorly treated with the currently available drugs, being urgent the need of innovative analgesics. In this frame, novel analogues of endomorphin-1 and dermorphin emerge as promising starting points to develop innovative, more effective analgesics to treat neuropathic pain. ⋯ This review reports that innovative opioid peptides will be of great help in better understanding the multifaceted scenario of neuropathic pain treatment, providing very interesting opportunities for the identification of novel and more effective opioid analgesics to be employed as medications.