Biology subjects

Ruiz, M. A.

Publications and source records attributed to Ruiz, M. A..

4 recordsLinked to original sources

bioRxiv2026

Melanocortin receptor 4 agonist setmelanotide treats opioid-induced respiratory depression

BackgroundThe primary cause of death associated with opioids is opioid-induced respiratory depression (OIRD). Naloxone is used to reverse OIRD, but this drug is a competitive antagonist of {micro}-opioid receptor (MOR) and reverses analgesia, which limits its therapeutic use. Alternative non-opioid receptor antagonist-based approaches to OIRD treatment and prevention are needed. The aim of this study was to evaluate if setmelanotide (SET) is capable of reversing OIRD in a mouse model. MethodsC57BL/6J male and female mice and Sprague-Dawley rats were given IP morphine or fentanyl and then treated 15 min later with either SET or vehicle VEH (IP) in a random order. Breathing was recorded by barometric plethysmography, and pain sensitivity was measured by the tail-flick test. ResultsIn mice with OIRD, SET induced a 3-fold reduction of the apnea index, and decreased apnea duration as compared to the VEH treatment. SET increased respiratory rate and did not affect opioid-induced analgesia. Photostimulation of MC4R+ ChR2-expressing fibers in the parafacial region of MC4R-Cre mice elicited short-latency excitatory postsynaptic current in rostral ventral respiratory group (rVRG) pre-motoneurons projecting to the phrenic nucleus in the C3-C4 ventral horns of the spinal cord. Fentanyl inhibited the activity of rVRG neurons and SET reversed this effect. ConclusionsSET effectively treated OIRD by increasing respiratory rate and inducing a significant decrease in the number of apneas without decreasing analgesia.

physiology↗

bioRxiv2025

Glucose promotes neuron morphology abnormalities and egg-laying defects dependentofthe serotonin signaling pathway in Caenorhabditis elegans

A chronic hyperglycemic state can lead to neuropathological complications such as permanent nerve damage. Neuropathology is a debilitating ailment that affects nearly half of the individuals with diabetes, underscoring the relevance to investigate the impact of diet and glucose levels on the nervous system. Using the genetic model system Caenorhabditis elegans, we determined that a diet rich in glucose impacts biological processes dependent on neuronal function. The rate of intrauterine egg-hatching increased in animals fed a glucose diet and the inhibition of dopamine or serotonin is sufficient to counteract the impact of the glucose diet. The glucose-induced intrauterine egg-hatching phenotype is independent of the SER-1 and SER-7 receptors yet dependent on the DAF16/FOXO transcription factor. Furthermore, animals fed a glucose-supplemented diet displayed abnormal morphologies in the HSN and NSM serotonergic neurons and the HSN displayed axonal degeneration, which is a prominent pathological feature in neurological dysfunction and disease. Combined these data indicate that a glucose-diet affects nervous system and signaling pathways in C. elegans, which can be used to further model diet-induced neuropathy.

genetics↗

bioRxiv2023

Effect of the LSD1 Inhibitor RN-1 on gamma;-globin and Global Gene Expression during Erythroid Differentiation in Baboons (Papio anubis)

Increased levels of Fetal Hemoglobin reduce the severity of symptoms of patients with sickle cell disease and decrease the risk of death. An affordable, small molecule drug that stimulates HbF expression in vivo would be ideally suited to treat the large numbers of SCD patients that exist worldwide. Our previous work showed that administration of the LSD1 (KDM1A) inhibitor RN-1 to normal baboons increased Fetal Hemoglobin (HbF) and was tolerated over a prolonged treatment period. HbF elevations were associated with changes in epigenetic modifications that included increased levels of H3K4 di-and tri-methyl lysine at the {gamma}-globin promoter. While dramatic effects of the loss of LSD1 on hematopoietic differentiation have been observed in murine LSD1 gene deletion and silencing models, the effect of pharmacological inhibition of LSD1 in vivo on hematopoietic differentiation is unknown. The goal of these experiments was to investigate the in vivo mechanism of action of the LSD1 inhibitor RN-1 by determining its effect on {gamma}-globin expression in highly purified subpopulations of bone marrow erythroid cells enriched for varying stages of erythroid differentiation isolated directly from baboons treated with RN-1 and also by investigating the effect of RN1 on the global transcriptome in a highly purified population of proerythroblasts. Our results show that RN-1 administered to baboons targets an early event during erythroid differentiation responsible for {gamma}-globin repression and increases the expression of a limited number of genes including genes involved in erythroid differentiation such as GATA2, GFi-1B, and LYN.

molecular biology↗

bioRxiv2018

Crohn’s disease patients effectively mobilize peripheral blood stem cells to perform autologous haematopoietic stem cell transplantation

BackgroundTreatment with high doses chemotherapy followed by autologous haematopoietic stem cell transplantation is promising for refractory Crohns disease patients with no therapeutic option and at imminent risk of further surgeries.\n\nObjectivesTo evaluate the feasibility and efficacy of haematopoietic progenitor cell mobilization in a group of Crohns disease patients preparing for autologous unselected haematopoietic stem cell transplantation in a single institution. This is the first study to evaluate mobilization for Crohns disease.\n\nMethodsPatients were selected according to criteria of the European Bone Marrow Transplant Society.\n\nResultsAll patients mobilized with the mean number of haematopoietic progenitor cells obtained and infused being 16.17 x 106/CD34+/kg. Most patients required only one leukapheresis session to reach the ideal number of cells. Grafting occurred around ten days after cells infusion. Complications and adverse events during the mobilization period were rare with only one patient presenting sepsis as a relevant event in the period.\n\nMost patients 20 (70%) had anaemia from the beginning of the mobilization but only 11 (37.9%) received packed red blood cell transfusions.\n\nConclusionMobilization in patients with Crohns disease is effective and it seems they are good mobilizers.

clinical trials↗