Uncontrolled diabetes results in several metabolic alterations including hyperglycemia. Indeed, several preclinical and clinical studies have suggested that this condition may induce susceptibility and the development of more aggressive infectious diseases, especially those caused by some bacteria (includingChlamydophila pneumoniae, Haemophilus influenzae, andStreptococcus pneumoniae, among others) and viruses [such as coronavirus 2 (CoV2), Influenza A virus, Hepatitis B, etc.]. Although the precise mechanisms that link glycemia to the exacerbated infections remain elusive, hyperglycemia is known to induce a wide array of changes in the immune system activity, including alterations in: (i) the microenvironment of immune cells (e.g.,pH, blood viscosity and other biochemical parameters); (ii) the supply of energy to infectious bacteria; (iii) the inflammatory response; and (iv) oxidative stress as a result of bacterial proliferative metabolism. Consistent with this evidence, some bacterial infections are typical (and/or have a worse prognosis) in patients with hypercaloric diets and a stressful lifestyle (conditions that promote hyperglycemic episodes). On this basis, the present review is particularly focused on: (i) the role of diabetes in the development of some bacterial and viral infections by analyzing preclinical and clinical findings; (ii) discussing the possible mechanisms by which hyperglycemia may increase the susceptibility for developing infections; and (iii) further understanding the impact of hyperglycemia on the immune system.

The G protein-coupled receptor 55 (GPR55) is a mammalian orphan receptor whose functions in the central nervous system (CNS) have been scarcely elucidated. Several endogenous lipids (cannabinoids and non-cannabinoid) may activate GPR55; these facts have raised a discussion about its nature as a putative cannabinoid receptor. Lysophosphatidylinositol (LPI) is a non-endocannabinoid lipid with activity as a full and potent agonist of GPR55. Beyond this controversy, it is known the endocannabinoid system and GPR55 are highly related both in anatomical localization and function. Peripherally, GPR55 participates in bone physiology, cardiovascular function, intestinal activity, pain regulation among others. In the brain, GPR55 high expression has been reported in the striatum and frontal cortex. Striatal GPR55 seems to participate in the formation of procedural memories in rats, but no information has been reported so far about its function in the cortex. However, GPR55 seems to play a role during axonal navigation and fine-tuning of synapses in other brain areas. GPR55 mRNA is expressed in the hippocampus, hypothalamus, frontal cortex and cerebellum, but only some speculative information about its function in these regions has been suggested. Therefore, the purpose of this review is to discuss the experimental information available about GPR55 function in the central nervous system.

Introduction: Migraine is a neurovascular disorder. Current acute specific antimigraine pharmacotherapies target trigeminovascular 5-HT_1B/1D, 5-HT_1F and CGRP receptors but, unfortunately, they induce some cardiovascular and central side effects that lead to poor treatment adherence/compliance. Therefore, new antimigraine drugs are being explored. Areas covered: This review considers the adverse (or potential) side effects produced by current and prospective antimigraine drugs, including medication overuse headache (MOH) produced by ergots and triptans, the side effects observed in clinical trials for the new gepants and CGRP antibodies, and a section discussing the potential effects resulting from disruption of the cardiovascular CGRPergic neurotransmission. Expert opinion: The last decades have witnessed remarkable developments in antimigraine therapy, which includes acute (e.g. triptans) and prophylactic (e.g. β-adrenoceptor blockers) antimigraine drugs. Indeed, the triptans represent a considerable advance, but their side effects (including nausea, dizziness and coronary vasoconstriction) preclude some patients from using triptans. This has led to the development of the ditans (5-HT_1F receptor agonists), the gepants (CGRP receptor antagonists) and the monoclonal antibodies against CGRP or its receptor. The latter drugs represent a new hope in the antimigraine armamentarium, but as CGRP plays a role in cardiovascular homeostasis, the potential for adverse cardiovascular side effects remains latent.

Background: Marijuana extracts (cannabinoids) have been used for several millennia for pain treatment. Regarding the site of action, cannabinoids are highly promiscuous molecules, but only two cannabinoid receptors (CB₁ and CB₂) have been deeply studied and classified. Thus, therapeutic actions, side effects and pharmacological targets for cannabinoids have been explained based on the pharmacology of cannabinoid CB₁/CB₂ receptors. However, the accumulation of confusing and sometimes contradictory results suggests the existence of other cannabinoid receptors. Different orphan proteins (e.g., GPR18, GPR55, GPR119, etc.) have been proposed as putative cannabinoid receptors. According to their expression, GPR18 and GPR55 could be involved in sensory transmission and pain integration. Methods: This article reviews select relevant information about the potential role of GPR18 and GPR55 in the pathophysiology of pain. Results: This work summarized novel data supporting that, besides cannabinoid CB₁ and CB₂ receptors, GPR18 and GPR55 may be useful for pain treatment. Conclusion: There is evidence to support an antinociceptive role for GPR18 and GPR55.

Introduction: Global increase in the consumption of antibiotics has induced selective stress on wild-type microorganisms, pushing them to adapt to conditions of higher antibiotic concentrations, and thus an increased variety of resistant bacterial strains have emerged. Metal nanoparticles synthesized by green methods have been studied and proposed as potential antimicrobial agents against both wild-type and antibiotic-resistant strains; in addition, exopolysaccharides have been used as capping agent of metal nanoparticles due to their biocompatibility, reducing biological risks in a wide variety of applications. Purpose: In this work, we use an exopolysaccharide, from Rhodotorula mucilaginosa UANL-001L, an autochthonous strain from the Mexican northeast, as a capping agent in the synthesis of Zn, and Ni, nanoparticle biopolymer biocomposites. Materials and methods: To physically and chemically characterize the synthesized biocomposites, FT-IR, UV-Vs, TEM, SAED and EDS analysis were carried out. Antimicrobial and antibiofilm biological activity were tested for the biocomposites against two resistant clinical strains, a Gram-positive Staphylococcus aureus, and a Gram-negative Pseudomonas aeruginosa. Antimicrobial activity was determined using a microdilution assay whereas antibiofilm activity was analyzed through crystal violet staining. Results: Biocomposites composed of exopolysaccharide capped Zn and Ni metal nanoparticles were synthesized through a green synthesis methodology. The average size of the Zn and Ni nanoparticles ranged between 8 and 26 nm, respectively. The Ni-EPS biocomposites showed antimicrobial and antibiofilm activity against resistant strains of Staphylococcus aureus and Pseudomonas aeruginosa at 3 and 2 mg/mL, respectively. Moreover, Zn-EPS biocomposites showed antimicrobial activity against resistant Staphylococcus aureus at 1 mg/mL. Both biocomposites showed no toxicity, as renal function showed no differences between treatments and control in the in vivo assays with male rats tests in this study at a concentration of 24 mg/kg of body weight. Conclusion: The exopolysaccharide produced by Rhodotorula mucilaginosa UANL-001L is an excellent candidate as a capping agent in the synthesis of biopolymer-metal nanoparticle biocomposites. Both Ni and Zn-EPS biocomposites demonstrate to be potential contenders as novel antimicrobial agents against both Gram-negative and Gram-positive clinically relevant resistant bacterial strains. Moreover, Ni-EPS biocomposites also showed antibiofilm activity, which makes them an interesting material to be used in different applications to counterattack global health problems due to the emergence of resistant microorganisms.