👤 Roberto Romero

Alzheimer disease (AD) is a progressive neurodegenerative disorder that predominantly affects the aging population. Anti-amyloid β (anti-Aβ) therapies, such as lecanemab, have been developed to slow disease progression. However, their use is occasionally associated with amyloid-related imaging abnormalities (ARIA), posing prominent clinical challenges. It has been shown that apolipoprotein E ( This retrospective study evaluated patients with AD who underwent A total of 85 patients were included in the study with rare genotypes excluded from analysis (3 patients). Among the common genotypes, e3/e4 was the most prevalent (55%). Statistical analysis revealed significant association between In this cohort of patients with AD being evaluated for lecanemab therapy, a significant association was identified between Show less

Investigating the genetic underpinnings of functional brain connectivity is essential to understand how genetic variation influences brain health and disease. Here, a mass-univariate approach was adopted to study the genetic architecture of functional brain circuitry (N Show less

Cleft lip with or without cleft palate (CL ± P) is a common congenital anomaly with complex genetic origins. This study presents a genetic case series of three Ecuadorian families with non-syndromic cleft lip and/or palate analyzed using whole-exome sequencing (WES). We identified rare or novel variants in genes with established or emerging roles in craniofacial development. Bioinformatic analyses—while not supported by functional validation—helped prioritize several candidate variants, including a novel These findings provide exploratory genetic data from an underrepresented Latin American population and highlight the need to include diverse cohorts in genomic research to improve diagnosis and genetic counseling. The online version contains supplementary material available at 10.1186/s12903-026-07796-8. Show less

Postnatal hippocampal neurogenesis is essential for learning and memory. Hippocampal neural precursor cells (NPCs) can be induced to proliferate and differentiate into either glial cells or dentate granule cells. Notably, hippocampal neurogenesis decreases dramatically with age, partly due to a reduction in the NPC pool and a decrease in their proliferative activity. Alpha-melanocyte-stimulating hormone (α-MSH) improves learning, memory, neuronal survival and plasticity. Here, we used postnatally-isolated hippocampal NPCs from Wistar rat pups (male and female combined) to determine the role of the melanocortin analog [Nle Show less

Sacha Inchi oil (SIO) and hybrid palm oil (HPO) are potential sources of unsaturated fatty acids to improve the lipid profile of dairy products. This study evaluated, for the first time, the effects of the daily consumption of yogurts with enhanced fatty acid profiles on plasma lipids related to cardiovascular disease (CVD) risk factors. A pilot, randomized, double-blind, parallel-controlled trial was conducted with 47 participants assigned to three groups: SIO-enriched yogurt (Group A), HPO-enriched yogurt (Group B), and plain yogurt (Group C). Fasting blood samples were collected at baseline and after 1, 2, and 3 months to measure plasma lipids (TC, LDL-C, HDL-C, and TAG), ApoA1, and ApoB. While no significant changes were observed in the overall lipid profiles, notable within-group effects were identified. The total cholesterol (TC) dropped by 2.8%, 1.3%, and 3.3%, and LDL-C by 1.6%, 2.5%, and 2% in Groups A, B, and C, respectively. Additionally, the intake of monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), and vitamin E significantly increased in Groups A and B. These results suggest that SIO and HPO can be used as milk fat substitutes to enhance the nutritional profile of yogurts without affecting CVD biomarkers in healthy individuals. Show less

Preeclampsia is a heterogeneous syndrome of diverse etiologies and molecular pathways leading to distinct clinical subtypes. Herein, we aimed to characterize the extracellular vesicle (EV)-associated and soluble fractions of the maternal plasma proteome in patients with preeclampsia and to assess their value for disease prediction. This case-control study included 24 women with term preeclampsia, 23 women with preterm preeclampsia, and 94 healthy pregnant controls. Blood samples were collected from cases on average 7 weeks before the diagnosis of preeclampsia and were matched to control samples. Soluble and EV fractions were separated from maternal plasma; EVs were confirmed by cryo-EM, NanoSight, and flow cytometry; and 82 proteins were analyzed with bead-based, multiplexed immunoassays. Quantile regression analysis and random forest models were implemented to evaluate protein concentration differences and their predictive accuracy. Preeclampsia subgroups defined by molecular profiles were identified by hierarchical cluster analysis. Significance was set at p < 0.05 or false discovery rate-adjusted q < 0.1. In preterm preeclampsia, PlGF, PTX3, and VEGFR-1 displayed differential abundance in both soluble and EV fractions, whereas angiogenin, CD40L, endoglin, galectin-1, IL-27, CCL19, and TIMP1 were changed only in the soluble fraction (q < 0.1). The direction of changes in the EV fraction was consistent with that in the soluble fraction for nine proteins. In term preeclampsia, CCL3 had increased abundance in both fractions (q < 0.1). The combined EV and soluble fraction proteomic profiles predicted preterm and term preeclampsia with an AUC of 78% (95% CI, 66%-90%) and 68% (95% CI, 56%-80%), respectively. Three clusters of preeclampsia featuring distinct clinical characteristics and placental pathology were identified based on combined protein data. Our findings reveal distinct alterations of the maternal EV-associated and soluble plasma proteome in preterm and term preeclampsia and identify molecular subgroups of patients with distinct clinical and placental histopathologic features. Show less

To evaluate changes in blood long-chain polyunsaturated fatty acid (LCPUFA) and oxylipin concentrations in very preterm infants from birth to 36 weeks' postmenstrual age (WPA) after providing an emulsified arachidonic acid (ARA):docosahexaenoic acid (DHA) supplement at two different concentrations. This prospective, randomized trial assigned infants to receive a supplement (1) 80:40 group (80 mg/kg/day ARA and 40 mg/kg/day DHA, Gestational age was similar between groups (80:40 = 28 Supplementation at high doses (120:60 mg/kg/day) increased levels of ARA, and EPA- and ARA-derived oxylipins compared to low doses (80:40 mg/kg/day). Differences were detected in EPA metabolites without a significant increase in plasma DHA. Show less

The relationship between cancer and autoimmunity is complex. However, the incidence of solid tumors such as melanoma has increased significantly among patients with previous or newly diagnosed systemic autoimmune disease (AID). At the same time, immune checkpoint blockade (ICB) therapy of cancer induces Show less

Understanding molecular basis involved in overweight is an important first step in developing therapeutic pathways against excess in body weight gain. The purpose of our pilot study was to evaluate the gene expression profiles in the peripheral blood of obese patients without other metabolic complications. A sample of 17 obese patients without metabolic syndrome and 15 non obese control subjects was evaluated in a prospective way. Following 'One-Color Microarray-Based Gene Expression Analysis' protocol Version 5.7 (Agilent p/n 4140-90040), cRNA was hybridized with Whole Human Genome Oligo Microarray Kit (Agilent p/n G2519F-014850) containing 41,000+ unique human genes and transcripts. The average age of the study group was 43.6 ± 19.7 years with a sex distribution of 64.7% females and 35.3% males. No statistical differences were detected with healthy controls 41.9 ± 12.3 years with a sex distribution of 70% females and 30% males. Obese patients showed 1436 genes that were differentially expressed compared to control group. Ingenuity Pathway Analysis showed that these genes participated in 13 different categories related to metabolism and cellular functions. In the gene set of cellular function, the most important genes were C-terminal region of Nel-like molecule 1 protein (NELL1) and Pigment epithelium-derived factor (SPEDF), both genes were over-expressed. In the gene set of metabolism, insulin growth factor type 1 (IGF1), ApoA5 (apolipoprotein subtype 5), Foxo4 (Forkhead transcription factor 4), ADIPOR1 (receptor of adiponectin type 1) and AQP7 (aquaporin channel proteins7) were over expressed. Moreover, PIKFYVE (PtdIns(3) P 5-kinase), and ROCK-2 (rho-kinase II) were under expressed. We showed that PBMCs from obese subjects presented significant changes in gene expression, exhibiting 1436 differentially expressed genes compared to PBMCs from non-obese subjects. Furthermore, our data showed a number of genes involved in relevant processes implicated in metabolism, with genes presenting high fold-change values (up-regulation and down regulation) associated with lipid, carbohydrate and protein metabolism. Show less

Major Depressive Disorder (MDD) is a common psychiatric disorder for which available medications are often not effective. The high prevalence of MDD and modest response to existing therapies compels efforts to better understand and treat the disorder. Decreased hippocampal volume with increasing duration of depression suggests altered gene expression or even a decrease in neurogenesis. Tissue punches from the dentate gyrus were collected postmortem from 23 subjects with MDD and 23 psychiatrically-normal control subjects. Total RNA was isolated and whole transcriptome paired-end RNA-sequencing was performed using an Illumina NextSeq 500. For each sample, raw RNA-seq reads were aligned to the Ensembl GRCh38 human reference genome. Analysis revealed 30 genes differentially expressed in MDD compared to controls (FDR<0.05). Down-regulated genes included several with inflammatory function (ISG15, IFI44L, IFI6, NR4A1/Nur-77) and GABBR1 while up-regulated genes included several with cytokine function (CCL2/MCP-1), inhibitors of angiogenesis (ADM, ADAMTS9), and the KANSL1 gene, a histone acetyltransferase. Similar analyses of specific subsets of MDD subjects (suicide vs. non-suicide, single vs. multiple episodes) yielded similar, though not identical, results. Enrichment analysis identified an over-representation of inflammatory and neurogenesis-related (ERK/MAPK) signaling pathways significantly altered in the hippocampal dentate gyrus in MDD. Together, these data implicate neuro-inflammation as playing a crucial role in MDD. These findings support continued efforts to identify adjunctive approaches towards the treatment of MDD with drugs including anti-inflammatory and neuroprotective properties. Show less

Abruptio placentae is a complex multifactorial disease that is associated with maternal and neonatal death and morbidity. Abruptio placentae's high recurrence rate, high prevalence of heritable thrombophilia among women with abruptio placentae, and aggregation of cases in families of women with the disease support the possibility of a genetic predisposition. Previous genome-wide and candidate gene association studies have identified single nucleotide polymorphisms in mitochondrial biogenesis and oxidative phosphorylation genes that potentially are associated with abruptio placentae risk. Perturbations in mitochondrial biogenesis and oxidative phosphorylation, which results in mitochondrial dysfunction, can lead to the impairment of differentiation and invasion of the trophoblast and to several obstetrics complications that include abruptio placentae. The purpose of this study was to determine whether the results of a candidate genetic association study that indicated a link between DNA variants (implicated in mitochondrial biogenesis and oxidative phosphorylation) and abruptio placentae could be replicated. The study was conducted among participants (507 abruptio placentae cases and 1090 control subjects) of the Placental Abruption Genetic Epidemiology study. Weighted genetic risk scores were calculated with the use of abruptio placentae risk-increasing alleles of 11 single nucleotide polymorphisms in 9 mitochondrial biogenesis and oxidative phosphorylation genes (CAMK2B, NR1H3, PPARG, PRKCA, THRB, COX5A, NDUFA10, NDUFA12, and NDUFC2), which previously was reported in the Peruvian Abruptio Placentae Epidemiology study, a study with similar design and study population to the Placental Abruption Genetic Epidemiology study. Logistic regression models were fit to examine associations of weighted genetic risk scores (quartile 1, <25th percentile; quartile 2, 25-50th percentile; quartile 3, 50-70th percentile, and quartile 4, >75th percentile) with risk of abruptio placentae, adjusted for population admixture (the first 4 principal components), maternal age, infant sex, and preeclampsia. The weighted genetic risk score was also modeled as a continuous predictor. To assess potential effect modification, analyses were repeated among strata that were defined by preeclampsia status, maternal age (≥35 vs 18-34 years), and infant sex. Abruptio placentae cases were more likely to have preeclampsia, shorter gestational age, and lower infant birthweight. Participants in quartile 2 (score, 12.6-13.8), quartile 3 (score, 13.9-15.0) and quartile 4 (score, ≥15.1) had a genetic risk score of 1.45-fold (95% confidence interval, 1.04-2.02; P=.03), a 1.42-fold (95% confidence interval, 1.02-1.98; P=.04), and a 1.75-fold (95% confidence interval, 1.27-2.42; P=7.0E-04) higher odds of abruptio placentae, respectively, compared with those in quartile 1 (score,<12.6; P-for trend=.0003). The risk of abruptio placentae was 1.12-fold (95% confidence interval, 1.05-1.19; P=3.0×10 In this study, we replicated previous findings and provide strong evidence for DNA variants that encode for genes that are involved in mitochondrial biogenesis and oxidative phosphorylation pathways, which confers risk for abruptio placentae. These results shed light on the mechanisms that implicate DNA variants that encode for proteins in mitochondrial function that are responsible for abruptio placentae risk. Therapeutic efforts to reduce risk of abruptio placentae can be enhanced by improved biologic understanding of maternal mitochondrial biogenesis/oxidative phosphorylation pathways and identification of women who would be at high risk for abruptio placentae. Show less

The strong male predominance in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) remains inadequately explained, but sex hormones might be involved. We hypothesized that single nucleotide polymorphisms (SNPs) in the androgen pathway influence risk of developing BE and EAC. This genetic-epidemiological analysis included 14 studies from Australia, Europe and North America. Polymorphisms in 16 genes coding for the androgen pathway were analyzed using a gene-based approach: versatile gene-based test association study. This method evaluates associations between a trait and all SNPs within a specific gene rather than each SNP marker individually as in a conventional GWAS. The data were stratified for sex, body-mass index, waist-to-hip ratio, tobacco smoking and gastroesophageal reflux status. Included were data from 1,508 EAC patients, 2,383 BE patients and 2,170 control participants. SNPs within the gene CYP17A1 were associated with risk of BE in the sexes combined (p = 0.002) and in males (p = 0.003), but not in females separately (p = 0.3). This association was found in tobacco smokers (p = 0.003) and in BE patients without reflux (p = 0.004), but not in nonsmokers (p = 0.2) or those with reflux (p = 0.036). SNPs within JMJD1C were associated with risk of EAC in females (p = 0.001). However, none of these associations replicated in a subsequent sample. Fourteen other genes studied did not reach statistically significant levels of association with BE, EAC or the combination of BE and EAC, after correcting for the number of genes included in the analysis. In conclusion, genetic variants in the androgen-related genes CYP17A1 and JMJD1C might be associated with risk of BE and EAC, respectively, but replication data with larger sample sizes are needed. Show less

Many types of human cancers having hyperactivated Wnt signaling display no causative alterations in known effectors of this pathway. Here, we report a function of TGIF in Wnt signaling. TGIF associates with and diverts Axin1 and Axin2 from the β-catenin destruction complex, therefore allowing β-catenin accrual. Intriguingly, activation of Wnt signaling induces the expression of TGIF, which unveils a feed-forward loop that ensures effective integration of Wnt signaling. In triple-negative breast cancers (TNBC), elevated levels of TGIF correlate with high Wnt signaling and poor survival of patients. Moreover, genetic experiments revealed that Tgif1 ablation impeded mammary tumor development in MMTV-Wnt1 mice, further underscoring a requirement of TGIF for oncogenic Wnt signaling. Show less

Congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders caused by genetic defects affecting neuromuscular transmission and leading to muscle weakness accentuated by exertion. Three different aspects have been investigated by members of the national French CMS Network: the difficulties in making a proper diagnosis; the course and long-term prognosis; and the response to therapy, especially for CMS that do not respond to cholinesterase inhibitors. CMS diagnosis is late in most cases because of confusion with other entities such as: congenital myopathies, due to the frequent presentation in patients of myopathies such as permanent muscle weakness, atrophy and scoliosis, and the abnormalities of internal structure, diameter and distribution of fibers (type I predominance, type II atrophy) seen on biopsy; seronegative autoimmune myasthenia gravis, when CMS is of late onset; and metabolic myopathy, with the presence of lipidosis in muscle. The long-term prognosis of CMS was studied in a series of 79 patients recruited with the following gene mutations: CHRNA; CHRNE; DOK7; COLQ; RAPSN; AGRN; and MUSK. Disease-course patterns (progressive worsening, exacerbation, stability, improvement) could be variable throughout life in a given patient. DOK7 patients had the most severe disease course with progressive worsening: of the eight wheelchair-bound and ventilated patients, six had mutations of this gene. Pregnancy was a frequent cause of exacerbation. Anticholinesterase agents are the first-line therapy for CMS patients, except for cases of slow-channel CMS, COLQ and DOK7. In our experience, 3,4-DAP was a useful complement for several patients harboring CMS with AChR loss or RAPSN gene mutations. Ephedrine was given to 18 patients (eight DOK7, five COLQ, four AGRN and one RAPSN). Tolerability was good. Therapeutic responses were encouraging even in the most severely affected patients, particularly with DOK7 and COLQ. Salbutamol was a good alternative in one patient who was allergic to ephedrine. Show less

The aim of this study was to analyze the effect of 2 antiplatelet regimens on the inhibition of GP IIb/IIIa-dependent platelet activation and their association with the poststenting inflammatory response. Seventeen patients with acute myocardial infarction were divided into 2 groups: (A) clopidogrel plus tirofiban infusion administered together during inclusion (n = 10); (B) clopidogrel administered at inclusion and followed 2 hours after by tirofiban (n = 7). Blood samples were obtained at inclusion and at 24 and 48 hours after stenting. Before stenting, a greater reduction of GP IIb/IIIa-dependent platelet activation was found in both groups, although it was greater in group A than in group B. This statistical difference was not observed at 24 and 48 hours after the procedure. At 48 hours after stenting, interleukin-6, interleukin-10, soluble intracellular adhesion molecule-1, and soluble CD40 ligand plasma values were not different between experimental groups. By proteomics, different isoforms of the following proteins were identified: alpha 1-antitrypsin (ATT-1), fibrinogen gamma chain, apolipoprotein A-IV, apolipoprotein A-I, vitamin D binding protein, haptoglobin, and serotransferrin. At 48 hours after stenting, only the plasma expression of the ATT-1 isoform 5 was significantly increased in group A compared with group B. In conclusion, a greater inhibition of GP IIb/IIIa-dependent platelet activation before stenting was not correlated with a different inflammatory activity early after stenting. Show less