👤 Miguel Del Campo

Fibromyalgia (FM) is a multifactorial syndrome involving chronic pain and psychological distress. Psychological traits such as anxiety, depression, and catastrophising are linked to symptom severity. Genetic variability may contribute to these dimensions through mechanisms related to pain modulation and stress response. To examine associations between selected genetic polymorphisms and psychological variables in women with FM. A cross-sectional study was conducted in 67 women diagnosed with FM. Pain intensity, FM impact and psychological variables-anxiety, depression and catastrophising-were assessed using validated questionnaires. Saliva samples were collected and 10 SNPs were genotyped (COMT rs4680, DRD3 rs6280, OPRM1 rs1799971, BDNF rs6265, MAOA rs1137070, FKBP5 rs1360780, IL6 rs1800796, TNF rs1800629, IL10 rs1800896, IFITM3 rs12252). Correlations were assessed using Pearson or Spearman coefficients, and associations were examined using ANOVA or Kruskal-Wallis with Tukey or Mann-Whitney post hoc tests. Pain intensity correlated with depression (r = 0.476, p < 0.001), catastrophising (r = 0.414, p < 0.001), and anxiety (r = 0.314, p = 0.009). Catastrophising was related to depression (r = 0.615, p < 0.001), anxiety (r = 0.453, p < 0.001), and kinesiophobia (r = 0.445, p < 0.001). BDNF rs6265 was associated with catastrophising (p = 0.044), OPRM1 rs1799971 with anxiety (p = 0.030), and MAOA rs1137070 with depression (p = 0.020). Psychological variables in FM are interrelated and linked to pain perception. BDNF, OPRM1 and MAOA polymorphisms are associated with indices of psychological vulnerability, underscoring the importance of integrating genetic and psychological perspectives to understand variability in FM. Genetic variability influences psychological vulnerability in fibromyalgia. Specific variants were associated with key psychological traits: BDNF rs6265 with pain catastrophising, OPRM1 rs1799971 with anxiety, and MAOA rs1137070 with depressive symptoms. These findings reveal an interplay between genetic and psychological factors that may guide more personalised strategies for managing fibromyalgia. Show less

Age-related hearing loss (ARHL) disrupts ascending auditory inputs, impairing auditory signal transmission, triggering cortical hyperexcitability, and increasing the risk of age-related cognitive decline. In early aging, multisession epidural direct current stimulation (DCS) of the auditory cortex (AC) preserves auditory thresholds and prevents cortical hyperexcitability in Wistar rats. Here, we hypothesized that multisession DCS could halt transcriptional dysregulation in the AC at the earliest stages of aging. We have characterized age-related transcriptional changes in the AC to assess DCS-mediated effects by RNA-seq. At 18.13 months, non-stimulated, aged rats (NES) showed 194 differentially expressed genes (DEGs) in relation to young controls (YG), with enrichment in pathways associated with GABAergic, glutamatergic, and dopaminergic synapses, long-term potentiation/depression, inflammaging, autophagy, apoptosis and neurodegeneration. The upregulated genes included Gabrb1, Grin2b, Rac3c, Tnr, and Ndst1, suggesting compensatory hyperactivity, excitatory/inhibitory imbalance, and stiffening of perineuronal nets (PNN) around parvalbumin (PV) interneurons. Electrically stimulated (ES) rats showed 86 DEGs in relation to YG, with no significant enrichment in aging-related pathways. By contrast, NES vs ES showed 1393 DEGs, with strong enrichment in aging-related pathways. Also, many of the 121 common DEGs across comparisons, which are upregulated in NES and downregulated in ES, are related to neurotransmission (Gabrb1, Grin2b), synaptic scaffolding (Dlg2, Prkca), trophic signaling (Ntrk2, Igf1r) and PNN (Tnr, Ndst1). Based on these findings, multisession DCS curbs maladaptive genomic reprogramming in the aged AC most likely by preserving excitatory/inhibitory balance and maintaining PNN integrity, thereby protecting the AC from ARHL and cognitive vulnerability. Show less

Increasing evidence indicates that β-secretase 1 (BACE1) activity and concentration in blood are candidate biomarkers for Alzheimer's disease (AD). Investigating potential demographic, biological, and clinical determinants of BACE1 in the blood matrix is the critical step to validate and qualify BACE1 bio-indicators for different contexts-of-use (CoU), such as risk assessment, early detection, diagnosis, prognosis, management of AD, and outcome of amyloid pathway targeted drugs. To evaluate the influence of age, sex, HDL-cholesterol and comorbidities (cardiovascular diseases, hypertension, diabetes) on circulating BACE-1 activity. prospective analysis of serum samples, clinical, biological, and demographic variables. Three cohorts: 1) Memory Clinic of the Department of Internal Medicine, S. Anna University Hospital, Ferrara (Italy); 2) outpatients attending the Menopause and Osteoporosis Centre (MOC) of the University of Ferrara (Ferrara, Italy); 3) Prevention Center of the University of Ferrara. 504 cognitively healthy individuals (median age: 62 years, interquartile range: 51-73) and 175 patients with AD (78 years, 74-82). serum BACE1 (sBACE1), age, sex, HDL-cholesterol, major comorbidities. Age was the strongest independent predictor of sBACE1 variance (β=0.425, p<0.0001), followed by sex (β=0.180, p<0.0001), high density lipoprotein-cholesterol (HDL-C) (β=-0.168, p<0.0001) and hypertension (β=0.111, p<0.05) (overall model, R2: 0.232). The probability of having elevated sBACE1 activity increased after 70 years of age, with women being more susceptible to higher sBACE1 activity than men. We provide evidence about potential clinical and biological determinants of sBACE1 activity with a strong association among biomarker, female sex, and older age. Show less

The main aim was to evaluate changes in urea cycle enzymes in NAFLD patients and in two preclinical animal models mimicking this entity. Seventeen liver specimens from NAFLD patients were included for immunohistochemistry and gene expression analyses. Three-hundred-and-eighty-two biopsy-proven NAFLD patients were genotyped for rs1047891, a functional variant located in carbamoyl phosphate synthetase-1 (CPS1) gene. Two preclinical models were employed to analyse CPS1 by immunohistochemistry, a choline deficient high-fat diet model (CDA-HFD) and a high fat diet LDLr knockout model (LDLr -/-). A significant downregulation in mRNA was observed in CPS1 and ornithine transcarbamylase (OTC1) in simple steatosis and NASH-fibrosis patients versus controls. Further, age, obesity (BMI > 30 kg/m Show less

T-cell lymphoblastic lymphoma (T-LBL) is an aggressive neoplasm closely related to T-cell acute lymphoblastic leukaemia (T-ALL). Despite their similarities, and contrary to T-ALL, studies on paediatric T-LBL are scarce and, therefore, its molecular landscape has not yet been fully elucidated. Thus, the aims of this study were to characterize the genetic and molecular heterogeneity of paediatric T-LBL and to evaluate novel molecular markers differentiating this entity from T-ALL. Thirty-three paediatric T-LBL patients were analyzed using an integrated approach, including targeted next-generation sequencing, RNA-sequencing transcriptome analysis and copy-number arrays. Copy number and mutational analyses allowed the detection of recurrent homozygous deletions of 9p/CDKN2A (78%), trisomy 20 (19%) and gains of 17q24-q25 (16%), as well as frequent mutations of NOTCH1 (62%), followed by the BCL11B (23%), WT1 (19%) and FBXW7, PHF6 and RPL10 genes (15%, respectively). This genetic profile did not differ from that described in T-ALL in terms of mutation incidence and global genomic complexity level, but unveiled virtually exclusive 17q25 gains and trisomy 20 in T-LBL. Additionally, we identified novel gene fusions in paediatric T-LBL, including NOTCH1-IKZF2, RNGTT-SNAP91 and DDX3X-MLLT10, the last being the only one previously described in T-ALL. Moreover, clinical correlations highlighted the presence of Notch pathway alterations as a factor related to favourable outcome. In summary, the genomic landscape of paediatric T-LBL is similar to that observed in T-ALL, and Notch signaling pathway deregulation remains the cornerstone in its pathogenesis, including not only mutations but fusion genes targeting NOTCH1. Show less

The role of macrophages (Mo) and their prognostic impact in diffuse large B-cell lymphomas (DLBCL) remain controversial. By regulating the lipid metabolism, Liver-X-Receptors (LXRs) control Mo polarization/inflammatory response, and their pharmacological modulation is under clinical investigation to treat human cancers, including lymphomas. Herein, we surveyed the role of LXRs in DLBCL for prognostic purposes. Comparing bulk tumors with purified malignant and normal B-cells, we found an intriguing association of NR1H3, encoding for the LXR-α isoform, with the tumor microenvironment (TME). CIBERSORTx-based purification on large DLBCL datasets revealed a high expression of the receptor transcript in M1-like pro-inflammatory Mo. By determining an expression cut-off of NR1H3, we used digital measurement to validate its prognostic capacity on two large independent on-trial and real-world cohorts. Independently of classical prognosticators, NR1H3 Show less

Photosynthetic picoeukaryotes contribute a significant fraction of primary production in the upper ocean. Micromonas pusilla is an ecologically relevant photosynthetic picoeukaryote, abundantly and widely distributed in marine waters. Grazing by protists may control the abundance of picoeukaryotes such as M. pusilla, but the diversity of the responsible grazers is poorly understood. To identify protists consuming photosynthetic picoeukaryotes in a productive North Pacific Ocean region, we amended seawater with living Show less

Williams-Beuren syndrome (WBS, OMIM-194050) is a neurodevelopmental disorder with multisystemic manifestations caused by a 1.55-1.83 Mb deletion at 7q11.23 including 26-28 genes. Reported endocrine and metabolic abnormalities include transient hypercalcaemia of infancy, subclinical hypothyroidism in ∼ 30% of children and impaired glucose tolerance in ∼ 75% of adult individuals. The purpose of this study was to further study metabolic alterations in patients with WBS, as well as in several mouse models, to establish potential candidate genes. We analysed several metabolic parameters in a cohort of 154 individuals with WBS (data available from 69 to 151 cases per parameter), as well as in several mouse models with complete and partial deletions of the orthologous WBS locus, and searched for causative genes and potential modifiers. Triglyceride plasma levels were significantly decreased in individuals with WBS while cholesterol levels were slightly decreased compared with controls. Hyperbilirubinemia, mostly unconjugated, was found in 18.3% of WBS cases and correlated with subclinical hypothyroidism and hypotriglyceridemia, suggesting common pathogenic mechanisms. Haploinsufficiency at MLXIPL and increased penetrance for hypomorphic alleles at the UGT1A1 gene promoter might underlie the lipid and bilirubin alterations. Other disturbances included increased protein and iron levels, as well as the known subclinical hypothyroidism and glucose intolerance. Our results show that several unreported biochemical alterations, related to haploinsufficiency for specific genes at 7q11.23, are relatively common in WBS. The early diagnosis, follow-up and management of these metabolic disturbances could prevent long-term complications in this disorder. Show less