Trimethylamine N-oxide (TMAO) is a metabolite produced by the gut microbiota and has been mainly associated with an increased incidence of cardiovascular diseases (CVDs) in humans. There are factors that affect one’s TMAO level, such as diet, drugs, age, and hormones, among others. Gut dysbiosis in the host has been studied recently as a new approach to understanding chronic inflammatory and degenerative diseases, including cardiovascular diseases, metabolic diseases, and Alzheimer’s disease. These disease types as well as COVID-19 are known to modulate host immunity. Diabetic and obese patients have been observed to have an increase in their level of TMAO, which has a direct correlation with CVDs. This metabolite is attributed to enhancing the inflammatory pathways through cholesterol and bile acid dysregulation, promoting foam cell formation. Additionally, TMAO activates the transcription factor NF-κB, which, in turn, triggers cytokine production. The result can be an exaggerated inflammatory response capable of inducing endoplasmic reticulum stress, which is responsible for various diseases. Due to the deleterious effects that this metabolite causes in its host, it is important to search for new therapeutic agents that allow a reduction in the TMAO levels of patients and that, thus, allow patients to be able to avoid a severe cardiovascular event. The present review discussed the synthesis of TMAO and its contribution to the pathogenesis of various inflammatory diseases.

Melatonin (MEL) is a pleiotropic indolamine that reaches multiple intracellular targets. Among these, MEL binds to calmodulin (CaM) with high affinity. In presence of Ca²⁺, CaM binds to CaM-dependent kinase II (CaMKII). The Ca²⁺-CaM/CaMKII pathway regulates a myriad of brain functions in different cellular compartments. Evidence showing the regulation of this cellular pathway by MEL is scarce. Thus, our main objective was to study the interaction of MEL with CaM and its effects on CaMKII activity in two microenvironments (aqueous and lipidic) naturally occurring within the cell. In addition, colocalization of MEL with CaM in vivo was explored in mice brain hippocampus. In vitro CaM-MEL interaction and the structural conformations of CaM in the presence of this indoleamine were assessed through electrophoretic mobility and isoelectric point. The functional consequence of this interaction was evaluated by measuring CaMKII activity. Ca²⁺-CaM-MEL increased the activity of CaMKII in aqueous buffer but reduced the kinase activity in lipid buffer. Importantly, MEL colocalizes in vivo with Ca²⁺-CaM in the hippocampus. Our evidence suggests that MEL regulates the key cellular Ca²⁺-CaM/CaMKII pathway and might explain why physiological MEL concentrations reduce CaMKII activity in some experimental conditions, while in others it drives biological processes through activation of this kinase.

The state of Chiapas has held the first place of extreme poverty in Mexico. The majority of Chiapas' municipalities are inhabited by marginalized, indigenous populations, who usually present diarrhea of unknown etiology. We evaluated the nutritional status, intestinal parasites, and common bacterial pathogens, including DEC (diarrheagenic Escherichia coli) strains, in 178 children under five years of age with a high (rural) and a moderate (urban) degree of marginalization. Z-scores for anthropometric indexes from the children were obtained, whereas intestinal parasites were investigated by using a direct coproparasitoscopic analysis and a concentration method. DEC strains were detected by polymerase chain reaction (PCR). The stunting prevalence in children from the rural and urban regions was 79.8 and 7.5%, respectively. Only children from rural municipalities were parasitized (72.6%), being Ascaris lumbricoides and Entamoeba histolytica/Entamoeba dispar the most prevalent parasites (57.1 and 38.1%, respectively). More than half of the children presented moderated ascariasis. Besides Giardia intestinalis, these parasites were associated with stunting. The prevalence of DEC strains was similar in both regions. Only children from the Chiapas Highlands (rural zone) exhibited high prevalences of stunting and intestinal parasites. A reevaluation of social development programs should be in place to address stunting and intestinal parasitoses, mainly in rural regions of Chiapas, to avoid adverse functional consequences on these children.

Major depressive disorder is a disabling disease with the number of affected individuals increasing each year. Current antidepressant treatments take between three to six weeks to be effective with forty percent of patients being resistant to treatment, making it necessary to search for new antidepressant treatments. Ketamine, a phencyclidine hydrochloride derivative, given intravenously, induces a rapid antidepressant effect in humans. In mice, it causes increased neurogenesis and antidepressant-like effects. However, it also produces psychomimetic effects in humans and in rodents increases the locomotor activity. In contrast, melatonin, a hormone secreted by the pineal gland and synthesized in extrapineal sites, increases new neuron formation and causes antidepressant-like effects in adult rodents with no collateral effects. Here, we assessed the effects of a non-effective dose of ketamine in combination with melatonin (KET/MEL), both on neurogenesis as well as on the antidepressant-like effect in mice. Our results showed that KET/MEL combination increased neurogenesis and produced antidepressant-like effects without altering locomotor activity after both single and triple administration protocols. Our data strongly suggest that KET/MEL combination could be used to simultaneously promote neurogenesis, reverting neuronal atrophy and inducing antidepressant-like effects.