Articles publicats (D-CM)

Repeated Administrations of Polyphenolic Extracts Prevent Chronic Reflexive and Non-Reflexive Neuropathic Pain Responses by Modulating Gliosis and CCL2-CCR2/CX3CL1-CX3CR1 Signaling in Spinal Cord-Injured Female Mice

2025-04-29T07:40:47Z

Repeated Administrations of Polyphenolic Extracts Prevent Chronic Reflexive and Non-Reflexive Neuropathic Pain Responses by Modulating Gliosis and CCL2-CCR2/CX3CL1-CX3CR1 Signaling in Spinal Cord-Injured Female Mice Bagó Mas, Anna; Korimová, Andrea; Bretová, Karolina; Deulofeu, Meritxell; Verdú Navarro, Enrique; Fiol Santaló, Núria; Dubový, Petr; Boadas i Vaello, Pere Neuropathic pain after spinal cord injury lacks any effective treatments, often leading to chronic pain. This study tested whether the daily administration of fully characterized polyphenolic extracts from grape stalks and coffee could prevent both reflexive and non-reflexive chronic neuropathic pain in spinal cord-injured mice by modulating the neuroimmune axis. Female CD1 mice underwent mild spinal cord contusion and received intraperitoneal extracts in weeks one, three, and six post-surgery. Reflexive pain responses were assessed weekly for up to 10 weeks, and non-reflexive pain was evaluated at the study's end. Neuroimmune crosstalk was investigated, focusing on glial activation and the expression of CCL2/CCR2 and CX3CL1/CX3CR1 in supraspinal pain-related areas, including the periaqueductal gray, rostral ventromedial medulla, anterior cingulate cortex, and amygdala. Repeated treatments prevented mechanical allodynia and thermal hyperalgesia, and also modulated non-reflexive pain. Moreover, they reduced supraspinal gliosis and regulated CCL2/CCR2 and CX3CL1/CX3CR1 signaling. Overall, the combination of polyphenols in these extracts may offer a promising pharmacological strategy to prevent chronic reflexive and non-reflexive pain responses by modifying central sensitization markers, not only at the contusion site but also in key supraspinal regions implicated in neuropathic pain. Overall, these data highlight the potential of polyphenolic extracts for spinal cord injury-induced chronic neuropathic pain

Longitudinal Analysis of Placental IRS1 DNA Methylation and Childhood Obesity

2025-04-11T11:26:45Z

Longitudinal Analysis of Placental IRS1 DNA Methylation and Childhood Obesity Gómez-Vilarrubla, Ariadna; Niubó-Pallàs, Maria; Mas Parés, Berta; Bonmatí Santané, Alexandra; Martínez-Calcerrada, José María; López Ibáñez, Beatriz; Peñas Cruz, Aaron; Zegher, Francis de; Ibáñez, Lourdes; López-Bermejo, Abel; Bassols Casadevall, Judit Accumulating evidence suggests that the predisposition to metabolic diseases is established in utero through epigenomic modifications. However, it remains unclear whether childhood obesity results from preexisting epigenomic alterations or whether obesity itself induces changes in the epigenome. This study aimed to identify DNA methylation marks in the placenta associated with obesity-related outcomes in children at age 6 and to assess these marks in blood samples at age 6 and whether they correlate with obesity-related outcomes at that time. Using an epigenome-wide DNA methylation microarray on 24 placental samples, we identified differentially methylated CpGs (DMCs) associated with offspring BMI-SDS at 6 years. Individual DMCs were validated in 147 additional placental and leukocyte samples from children at 6 years of age. The methylation and/or gene expression of IRS1 in both placenta and offspring leukocytes were significantly associated with various metabolic risk parameters at age 6 (all p ≤ 0.05). Logistic regression models (LRM) and machine learning (ML) models indicated that IRS1 methylation in the placenta could strongly predict offspring obesity. Our results suggest that IRS1 may serve as a potential biomarker for the prediction of obesity and metabolic risk in children

Soluble receptors for advanced glycation endproducts are predictors of insulin sensitivity and affected by weight loss

2025-04-11T07:19:02Z

Soluble receptors for advanced glycation endproducts are predictors of insulin sensitivity and affected by weight loss Moreno Navarrete, José María; Leal Moncada, Yenny Teresa; Rosell Díaz , Marisel; Fernández-Real Lemos, José Manuel Background Mice experiments have underscored the efficacy of pharmacological inhibition of advanced glycation endproducts (AGEs) through the use of soluble receptors for advanced glycation endproducts (sRAGE) in mitigating obesity-linked metabolic disruptions and insulin resistance. However, human studies have presented conflicting findings regarding the correlation between circulating sRAGE levels and insulin resistance, as well as glucose tolerance. Here, we aimed to delve deeper into the relationship between sRAGE levels and systemic insulin sensitivity. Methods Plasma sRAGE levels, hyperinsulinemic-euglycemic clamp, and continuous glucose monitoring were measured in two independent cross-sectional case-control studies [cohort 1 (n = 180) and cohort 2 (n = 124)]. In addition, a subgroup of 42 participants with obesity were followed for 12 months. In 14 of these participants, weight loss was achieved through bariatric surgery intervention. Results Our results revealed a significant association between plasma sRAGE levels and both insulin sensitivity and glycemic control parameters, even after adjustments for age, sex, and BMI. Furthermore, longitudinal analysis demonstrated that interventions aimed at weight loss led to reductions in fasting glucose and HbA1c levels, concurrently with increases in sRAGE levels. Conclusions These findings underscore that sRAGE levels were strongly associated with insulin sensitivity and glycemic control, suggesting a possible role of sRAGE in preserving insulin sensitivity and maintaining glycemic control, which should be confirmed in further studies

Health-Related Quality of Life in Men with Fractures and Fear of Falling in General Population: A Cross-Sectional Study

2025-03-14T09:20:39Z

Health-Related Quality of Life in Men with Fractures and Fear of Falling in General Population: A Cross-Sectional Study Zwart Salmerón, Marta; Azagra Ledesma, Rafael; Díaz Herrera, Miguel Ángel; Pujol Salud, Jesús; Sáez Zafra, Marc; Aguyé Batista, Amada Purpose: This study aims to assess how fractures and fear of falling affect health-related quality of life (HRQoL) in men (≥50 years) across different domains. Methods: Design: Observational study. Setting: Primary care. Subjects: 237 men aged 50–90 years. Outcome measures: Age, frac-tures, fear of falling, EQ-5D. Results: A total of 122 men (51.47% of the male cohort) participated, the mean age was 69 ± 5 (≥65–74 years 26.2%, ≥75–84 years 21.3%, ≥85 years 9.8%). Poorer EQ-5D scores were observed in men ≥ 65 years with fractures in the pain domain (p = 0.04), while men < 65 showed better scores in mobility (p = 0.04), self-care (p = 0.04), daily activities (p = 0.04), and anxiety/depression (p = 0.01). Fear of falling significantly impacted HRQoL across all ages, with men ≥ 65 reporting worse mobility (p = 0.02) and higher anxiety/depression (p = 0.01), while men < 65 experienced less pain (p = 0.00). Conclusions: This study shows a relationship between frac-tures, fear of falling, and the perception of the various dimensions of HRQoL in older men. It highlights the need for targeted interventions and follow-up systems to monitor recovery and address fears of falling in men aged 65 and above post-fracture