👤 Naama Omer

The fat mass and obesity-associated (FTO) and melanocortin-4 receptor (MC4R) genes have been implicated in the pathophysiology of obesity. However, their regulatory behavior in human gastric tissue and association with postoperative weight loss following metabolic and bariatric surgery (MBS) remain unclear. In this prospective case-control study, gastric tissue from 50 patients with obesity undergoing laparoscopic sleeve gastrectomy and 48 non-obese controls was analyzed for FTO and MC4R mRNA expression using quantitative PCR. Adjusted Inverse propensity score weighting (IPSW-adjusted) and age-/sex-adjusted linear regression were applied. Receiver operating characteristic (ROC) curves were used to evaluate discriminatory thresholds. Correlation with 12-month percent total weight loss (%TWL) was assessed. FTO expression was significantly upregulated (mean fold-change: 4.68, p < 0.001) and MC4R downregulated (mean fold-change: - 0.91, p < 0.001) in patients with obesity. ROC analysis identified thresholds of > 1.515 for FTO (AUC = 1.00) and < 0.525 for MC4R (AUC = 1.00), both with high sensitivity and specificity. No significant correlation was observed between gene expression and %TWL at 12-month follow-up. Gastric expression of FTO and MC4R accurately discriminates between individuals with and without obesity but does not predict postoperative weight loss outcomes after sleeve gastrectomy. These findings indicate diagnostic potential, whereas prognostic value remains unsubstantial. Show less

Obesity is a complex, multifactorial disease influenced by genetic, hormonal, and metabolic factors. The fat mass and obesity-associated (FTO) and melanocortin 4 receptor (MC4R) genes have been implicated in body weight regulation through gut–brain signaling and their interactions with adipokines and enteroendocrine hormones. This study investigated the association between gastric expression of FTO and MC4R genes and circulating levels of leptin, adiponectin, and ghrelin in individuals with and without obesity. We conducted a case–control study including 50 patients with obesity undergoing sleeve gastrectomy and 50 controls undergoing diagnostic endoscopy. Gastric tissue gene expression was assessed by qRT-PCR, and serum hormone levels were quantified using ELISA. Inverse propensity score weighting was used to adjust for age and sex. FTO expression was significantly upregulated in patients with obesity (fold-change: 5.8 vs. 1.0, Show less

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by brain aggregates of amyloid-β (Aβ) plaques and Tau tangles. Despite extensive research, effective therapy for AD remains elusive. Polyoxometalates (POMs), a class of inorganic compounds with diverse chemical structures and properties, are emerging as potential candidates for AD treatment due to their ability to target key molecular players implicated in disease pathogenesis, such as Aβ, acetylcholinesterase (AChE) and butyryl acetylcholinesterase (BChE). Here, we use molecular docking to predict the binding pose and affinities of POMs to 10 top targets associated with AD. First, we validate our method by replicating experimentally known binding of POMs to Aβ (ΔG = - 9.67 kcal/mol), AChE (ΔG = - 9.39 kcal/mol) and BChE (ΔG = - 10.86 kcal/mol). Then, using this method, we show that POM can also bind β-secretase 1 (BACE1, ΔG = - 10.14 kcal/mol), presenilin 1 (PSEN1, ΔG = - 10.65 kcal/mol), presenilin 2 (PSEN2, ΔG = - 7.94 kcal/mol), Amyloid Precursor Protein (APP, ΔG = - 7.26 kcal/mol), Apolipoprotein E (APOE4, ΔG = - 10.05 kcal/mol), Microtubule-Associated Protein Tau (MAPT, ΔG = - 5.28 kcal/mol) depending on phosphorylation, and α-synuclein (SNCA, ΔG = - 7.64 kcal/mol). Through such binding, POMs offer the potential to mitigate APP cleavage, Aβ oligomer neurotoxicity, Aβ aggregation, thereby attenuating disease progression. Overall, our molecular docking study represents a powerful tool in the discovery of POM-based therapeutics for AD, facilitating the development of novel treatments for AD. Show less

Enteric nervous system development relies on intestinal colonization by enteric neural crest-derived cells (ENCDCs). This is driven by a population of highly migratory and proliferative ENCDCs at the wavefront, but the molecular characteristics of these cells are unknown. ENCDCs from the wavefront and the trailing region were isolated and subjected to RNA-seq. Wavefront-ENCDCs were transcriptionally distinct from trailing ENCDCs, and temporal modelling confirmed their relative immaturity. This population of ENCDCs exhibited altered expression of ECM and cytoskeletal genes, consistent with a migratory phenotype. Unlike trailing ENCDCs, the wavefront lacked expression of genes related to neuronal or glial maturation. As wavefront ENCDC genes were associated with migration and developmental immaturity, the genes that remain expressed in later progenitor populations may be particularly pertinent to understanding the maintenance of ENCDC progenitor characteristics. Dusp6 expression was specifically upregulated at the wavefront. Inhibiting DUSP6 activity prevented wavefront colonization of the hindgut, and inhibited the migratory ability of post-colonized ENCDCs from midgut and postnatal neurospheres. These effects were reversed by simultaneous inhibition of ERK signaling, indicating that DUSP6-mediated ERK inhibition is required for ENCDC migration in mouse and chick. Show less