Nanjing Children's Hospital Ltd.

Osteosarcoma is a common bone tumor in adolescents, which is characterized by lipid metabolism disorders and plays a key role in tumorigenesis and disease progression. Ferroptosis is an iron-dependent form of programmed cell death associated with lipid peroxidation. This review provides an in-depth analysis of the complex relationship between lipid metabolic reprogramming and associated ferroptosis in OS from the perspective of metabolic enzymes and metabolites. We discussed the molecular basis of lipid uptake, synthesis, storage, lipolysis, and the tumor microenvironment, as well as their significance in OS development. Key enzymes such as adenosine triphosphate-citrate lyase (ACLY), acetyl-CoA synthetase 2 (ACSS2), fatty acid synthase (FASN) and stearoyl-CoA desaturase-1 (SCD1) are overexpressed in OS and associated with poor prognosis. Based on specific changes in metabolic processes, this review highlights potential therapeutic targets in the lipid metabolism and ferroptosis pathways, and in particular the HMG-CoA reductase inhibitor simvastatin has shown potential in inducing apoptosis and inhibiting OS metastasis. Targeting these pathways provides new strategies for the treatment of OS. However, challenges such as the complexity of drug development and metabolic interactions must be overcome. A comprehensive understanding of the interplay between dysregulation of lipid metabolism and ferroptosis is essential for the development of innovative and effective therapies for OS, with the ultimate goal of improving patient outcomes.

Allergic rhinitis (AR), common in children and adolescents, involves Lysophosphatidylcholine acyltransferase 1 (LPCAT1) catalyzing surfactant lipid biosynthesis and suppressing endoplasmic reticulum expression. However, the precise mechanism underlying the impact of LPCAT1 on epithelial cell damage in AR remains elusive. Hence, the present investigation elucidated the potential effect of LPCAT1 on epithelial cell damage in AR by inhibiting endoplasmic reticulum stress. To assess cell viability, CCK8 assay was employed. Additionally, western blotting was utilized to evaluate the expression of endoplasmic reticulum stress-associated proteins ATF6, CHOP, p-eIF2α, p-IRE1, and LPCAT1. Subsequently, an interference plasmid targeting LPCAT1 was constructed, and western blot analysis was conducted to determine interference level of LPCAT1. An ELISA assay was employed to quantify the concentrations of TNFα, IL-1β, IL-6, GM-CSF, and eotaxin. Additionally, flow cytometry and western blotting techniques were utilized to evaluate cellular apoptosis, whereas immunofluorescence staining was applied to detect the expression levels of ZO-1. Our findings indicated that IL-13 stimulation resulted in an elevated expression of ER stress proteins and LPCAT1 in nasal mucosal epithelial cells. Furthermore, LPCAT1 interference diminished the expression of inflammatory mediators, apoptosis markers, barrier disruption indicators, and ER stress proteins in IL-13-stimulated nasal mucosal epithelial cells. Further, by inhibiting ER stress, LPCAT1 interference diminished the expression of inflammatory factors, apoptosis, and barrier damage in nasal mucosal epithelial cells stimulated by IL-13. Concisely, LPCAT1 ameliorates AR-induced inflammation, apoptosis, and barrier impairment in nasal mucosal epithelial cells by modulating ER stress, implying its potential as a novel therapeutic target for AR.

The ALMS1 gene is predominantly localized to cilia, particularly in the photoreceptor cells of the retina, auditory neurons, kidneys, and other ciliated structures. Pathogenic mutations in this gene cause Alstrom syndrome (AS), which is characterized by dilated cardiomyopathy, retinal degeneration, neurodeafness, and centripetal obesity. However, the genetic mechanism of the ALMS1 gene remains unclear. This study reports five cases of Chinese children with heterozygous variants in the ALMS1 gene, aiming to expand the genetic map of AS and provide insights into its pathogenesis.

Whole exome sequencing (WES) was performed on 128 children diagnosed with DCM. ALMS1 variants were identified, and their pathogenicity and conservation were analyzed using bioinformatics tools. A retrospective analysis of genotypephenotype associations was also conducted in conjunction with previously reported cases.

A total of eleven variants were identified in the five patients, including seven nonsense variants c.2035C > T(p.R679*), c.10825C > T(p.(R3609*)), c.5230C > T(p.(Q1744*)), c.3008C > A(p.(S1003*)), c.11686delG(p.(V3896*)), c.2090C > A(p.(S697*)), c.12373C > T(p.(Q4125*)), two frameshift variants c.10383delT(p.(I3461fs*48)), c.1685_c.1686insCAG(p.(D563fs*4)), and two missense variants c.12163C > G(p.(R4055G)) and c.7867G > A(p.A2623T). Cardiac ultrasound revealed improvements in left ventricular ejection fraction (LVEF) following treatment, although no significant change in nystagmus was observed.

This study expands the genetic spectrum of ALMS1 gene variants and reinforces their pathogenicity through bioinformatics analysis. Additionally, we emphasize the importance of comprehensive cardiac evaluation and genetic testing in patients with DCM presenting with nystagmus.