👤 Daniel Masri

Peripheral injury reprograms metabolism in spinal cord oligodendrocytes, initiating a molecular cascade that drives chronic pain via neuronal β-amyloid (Aβ) release. After injury, mouse spinal oligodendrocytes downregulate myelin protein synthesis and upregulate lipid biosynthesis-but reroute lipids toward neuroplastic remodeling and away from myelin maintenance. This metabolic reallocation disrupts myelin integrity and axonal function, causing neuronal accumulation of amyloid precursor protein, enhanced expression of its processing β-secretase BACE1, and local release of Aβ peptides. Blocking Aβ production or clearing Aβ deposits stops the transition to pain chronicity. Deleting the lysosomal lipid hydrolase NAAA in oligodendrocytes prevents both injury-induced Aβ production and chronic pain development. The findings identify an unexpected mechanistic link between chronic pain and Alzheimer's-like neurodegeneration, positioning Aβ as a target for therapeutic intervention. Show less

The genetic etiology of hypertrophic cardiomyopathy (HCM) and the critical role of sarcomeric variants in its pathogenesis are well recognized (1). Among these, loss-of-function variants in the myosin binding protein C gene ( This was a prospective, cross-sectional study of 100 adults (aged 18-65 years) with symptomatic Pre-existing anti-AAV9 NAb were undetectable in 50% of patients. Among those with detectable titers (range: 1:10-1:720), only 16% exceeded 1:40. TAb were undetectable in 53%; titers ranged from 1:10 to 1:65,600. A strong correlation was observed between NAb and TAb titers (r = 0.671, Pre-existing immunity to AAV9 was absent or low in most Show less

Dyslipidemia is an important risk factor in CKD. The liver clears triglyceride-rich lipoproteins (TRL) Uninephrectomy- and aging-induced CKD in normotensive Wistar rats and hypertensive Munich-Wistar-Frömter (MWF) rats. Compared with 22-week-old sex- and strain-matched rats, 48-week-old uninephrectomized Wistar-CKD and MWF-CKD rats showed proteinuria, increased plasma creatinine, and hypercholesterolemia (all Progressive CKD induces hepatic HS elongation, leading to increased interaction with PCSK9. This might reduce hepatic lipoprotein uptake and thereby induce dyslipidemia in CKD. Therefore, PCSK9/HS may be a novel target to control dyslipidemia. Show less

Impaired adipose tissue insulin signalling is a critical feature of insulin resistance. Here we identify a pathway linking the lipolytic enzyme hormone-sensitive lipase (HSL) to insulin action via the glucose-responsive transcription factor ChREBP and its target, the fatty acid elongase ELOVL6. Genetic inhibition of HSL in human adipocytes and mouse adipose tissue results in enhanced insulin sensitivity and induction of ELOVL6. ELOVL6 promotes an increase in phospholipid oleic acid, which modifies plasma membrane fluidity and enhances insulin signalling. HSL deficiency-mediated effects are suppressed by gene silencing of ChREBP and ELOVL6. Mechanistically, physical interaction between HSL, independent of lipase activity, and the isoform activated by glucose metabolism ChREBPα impairs ChREBPα translocation into the nucleus and induction of ChREBPβ, the isoform with high transcriptional activity that is strongly associated with whole-body insulin sensitivity. Targeting the HSL-ChREBP interaction may allow therapeutic strategies for the restoration of insulin sensitivity. Show less

Evaluation of the paranasal sinuses is often performed in a purely clinical fashion, without the need for imaging. However, in certain instances imaging may be deemed valuable or even necessary in helping to solve a diagnostic dilemma, confirm a suspected diagnosis, evaluate the extent of a known condition, or assess for an underlying cause of the condition. Computed tomography (CT) and magnetic resonance imaging (MRI) can be useful in confirming a suspected diagnosis or providing additional information regarding causes or complications. CT and MRI play complementary roles in evaluating the rare tumors that may involve the paranasal sinuses. Show less