With the continuous development of messenger RNA (mRNA) technology, mRNA-based drugs have shown broad application prospects in recent years. Since mRNA is easy to be degraded and difficult to enter cells directly, the mRNA delivery vectors have always been one of the focuses in the development of mRNA-based drugs. Although lipid nanoparticles (LNPs) have been widely used for the delivery of mRNA, they tend to accumulate in the liver, and repeated administration can easily induce inflammatory response which leads to tissue damage. Compared with LNPs, virus-like particles (VLPs) have the advantages of high biocompatibility and safety, being expected to offer new solutions for mRNA delivery. Based on the practical application requirements, this review summarized the research progress in VLPs according to the mRNA delivery steps: particle assembly, delivery into cells, and intracellular release. We hope to provide a basis and design ideas for the development of new VLPs as delivery vectors, promote the application of VLPs in mRNA delivery, and provide new possibilities for the research and application of mRNA-based therapeutics.
RNA, Messenger/administration & dosage* ; Humans ; Nanoparticles/chemistry* ; Genetic Vectors ; Lipids/chemistry* ; Drug Delivery Systems/methods* ; Virion ; Animals ; Gene Transfer Techniques ; Liposomes

Perilla frutescens (L.) Britt. is a characteristic oil crop rich in polyunsaturated fatty acids, particularly α-linolenic acid, which has important development and utilization value. The Dof transcription factor is one of the plant-specific transcription factor families, which is widely involved in important biological processes such as plant growth, development, and metabolic regulation. In order to explore the key Dof transcription factors involved in the oil biosynthesis and systematically analyze their regulatory mechanisms of P. frutescens seeds, a total of 56 PfDof gene family members were identified from the genome and transcriptome data of P. frutescens and classified into four subfamilies according to sequence characteristics. All PfDofs contained highly conserved C₂-C₂ zinc finger domains, with gene duplication being the primary mechanism driving their evolution and expansion. Genes within the same subgroup exhibited similar gene structures and conserved motifs. The 56 PfDofs were predicted as unstable hydrophilic proteins, with α-helixes and random coils as their predominant structural components. The RNA-seq results revealed that 11 PfDofs exhibited differential expression during different developmental stages of P. frutescens seeds. RT-qPCR was performed to further validate the expression patterns of these 11 members across various tissue samples (root, stem, leaf, and flower) of P. frutescens and at different developmental stages of its seeds. The results showed that PfDof29 exhibited the highest expression level in seeds, which was consistent with the transcriptome data. Subcellular localization studies demonstrated that PfDof29 was localized to the nucleus and had a transcriptional activation activity. Overexpression of PfDof29 in Nicotiana tabacum resulted in a significant increase in total oil content of tobacco leaves, accompanied by reductions in starch and soluble sugar content, while the protein content remained unchanged. Additionally, the metabolic balance between saturated and unsaturated fatty acids in the transgenic tobacco leaves was altered, with a significant increase in α-linolenic acid content. The expression levels of the fatty acid desaturase genes NtFAD2, NtFAD3, and NtFAD8 were significantly upregulated. A yeast one-hybrid assay revealed that PfDof29 could directly bind to the promoter region of PfFAD8, thereby regulating its expression. This study provides an initial understanding of the regulatory mechanisms of PfDof transcription factors in the synthesis and accumulation of oil in P. frutescens. These findings offer new insights into the enhancement of oil content and quality of P. frutescens seeds.
Transcription Factors/physiology* ; Perilla frutescens/metabolism* ; Plant Proteins/metabolism* ; Gene Expression Regulation, Plant ; alpha-Linolenic Acid/biosynthesis* ; Lipids/biosynthesis* ; Seeds/genetics*

OBJECTIVE: To assess the association between the single nucleotide polymorphisms (SNP) rs174575 and rs2845574 of the fatty acid desaturase 2 (FADS2) gene and gestational diabetes mellitus (GDM). METHODS: A total of 1 514 pregnant women who visited West China Second University Hospital of Sichuan University between January 1, 2013 and December 31, 2021 were enrolled in this study. Among them, 583 were diagnosed with gestational diabetes mellitus (GDM group), and 931 had normal pregnancies (control group). The SNPs rs174575 and rs2845574 of the FADS2 gene were analyzed using Sanger DNA sequencing. Plasma levels of insulin (INS), apolipoprotein A1 (apoA1) and apolipoprotein B (apoB) were measured using enzymatic methods, chemiluminescence and immunoturbidimetry. This study was approved by the Medical Ethics Committee of the West China Second University Hospital of Sichuan University (Ethics No.: 2020-036). RESULTS: The main genotype at the rs174575 C/G and rs2845574 C/T loci were CC in both GDM and control groups. No significant difference was found between the GDM and control groups regarding the genotypic or allelic frequencies of rs174575 and rs2845574 sites (P > 0.05). Among the GDM group, individuals with the GG genotype at the rs174575 site had lower plasma HDL-C levels compared to those with the CC genotype (P < 0.05), and had higher atherogenic indices (AI) compared with the CC and CG genotype (P < 0.05; P < 0.05). Individuals with the TT genotype at the rs2845574 site had higher AI compared with the CT genotype (P < 0.05). Among the control group, individuals with the GG genotype had lower diastolic blood pressure (DBP) compared to those with the CC genotype (P < 0.05). Additional subgroup analysis demonstrated that the rs174575 polymorphism was associated with AI levels in obesity subgroup of GDM, TG levels in non-obese subgroup of control and DBP levels in the obese subgroup of control (P < 0.05; P < 0.05; P < 0.05). CONCLUSION The FADS2 rs174575 and rs2845574 polymorphisms in GDM patients are associated wit HDL-C and AI levels, and the FADS2 rs174575 polymorphisms was also associated with DBP levels in normal pregnant women. The AI and DBP levels have a BMI-dependent effect.
Humans ; Female ; Pregnancy ; Fatty Acid Desaturases/genetics* ; Polymorphism, Single Nucleotide ; Adult ; Diabetes, Gestational/blood* ; Blood Pressure/genetics* ; Lipids/blood* ; Genotype ; Genetic Predisposition to Disease

OBJECTIVES: To explore the lipidomic characteristics of children with bronchial asthma (hereafter referred to as asthma) and identify potential biomarkers for asthma. METHODS: A total of 26 asthmatic children were prospectively enrolled as the asthma group, and 20 healthy children served as the healthy control group. The asthma group was further divided into atopic (n=13) and non-atopic (n=13) subgroups based on IgE levels. Serum lipid metabolites were analyzed using liquid chromatography-mass spectrometry, followed by statistical analysis and data visualization. RESULTS: A total of 1 435 lipids were detected in the 46 children, primarily glycerophospholipids (625/1 435, 43.55%). Significant differences were observed in serum lipid profiles between the asthma and control groups. Twelve significantly differential lipids were identified, with receiver operating characteristic curve analysis showing that phosphatidylserine (PS)(18:0/20:4) and ceramide (Cer)(c16:0) exhibited the highest diagnostic value for asthma. The relative abundances of PS(18:0/20:4) and PS(18:0/22:6) were higher in the atopic subgroup than in the non-atopic subgroup (P<0.05) and positively correlated with total IgE levels in asthmatic children (r=0.675 and 0.740, respectively; P<0.05). CONCLUSIONS Asthmatic children exhibit significant lipid metabolic disturbances, primarily characterized by abnormal glycerophospholipid metabolism. Among these, PS(18:0/20:4) and Cer(c16:0) demonstrate specific alterations and may serve as potential diagnostic biomarkers for asthma. Furthermore, the positive correlation between PS(18:0/20:4) and PS(18:0/22:6) levels and serum total IgE suggests their possible involvement in immune regulation in asthma.
Humans ; Asthma/metabolism* ; Male ; Child ; Female ; Prospective Studies ; Mass Spectrometry/methods* ; Lipids/blood* ; Chromatography, Liquid/methods* ; Child, Preschool ; Immunoglobulin E/blood* ; Biomarkers/blood* ; Adolescent ; Liquid Chromatography-Mass Spectrometry

OBJECTIVES: To identify potential plasma lipidomic biomarkers that distinguish non-metastatic medulloblastoma (nmMB) from metastatic medulloblastoma (mMB) in children. METHODS: In this prospective study, 17 children with mMB and 20 matched children with nmMB were enrolled. Plasma samples were analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Lipid metabolites were evaluated for their associations and diagnostic performance. RESULTS: Orthogonal partial least squares discriminant analysis based on lipid profiles clearly separated nmMB from mMB, and 14 differential lipids were identified, including DG(18:2/20:4/0:0) and SM(d18:1/20:0). Receiver operating characteristic analysis showed nine metabolites with area under the curve greater than 0.7. Differential lipids were enriched in sphingolipid, glycerophospholipid, and arachidonic acid metabolism, suggesting an association with the metastatic phenotype. CONCLUSIONS Plasma lipidomics provides a new approach to identify mMB, and the identified lipid metabolites may support early diagnosis and treatment, prognostic assessment, and selection of therapeutic targets for metastatic medulloblastoma.
Humans ; Medulloblastoma/diagnosis* ; Lipidomics ; Child ; Male ; Female ; Child, Preschool ; Cerebellar Neoplasms/blood* ; Biomarkers, Tumor/blood* ; Neoplasm Metastasis ; Prospective Studies ; Adolescent ; Lipids/blood*

Sertoli cells play an important role in the process of spermatogenesis, and the abnormalities in spermatogenesis are closely related to disruptions in glycolipid metabolism. The metabolic environment of Sertoli cells is hypoxic, with glycolysis and fatty acid β-oxidation being the primary metabolic pathways. In Sertoli cells, glycolysis produces lactate to provide energy for spermatogenic cells, while fatty acid β-oxidation generates ATP. Currently, the relationship between glycolipid metabolism in Sertoli cells and spermatogenic cell development, as well as the interplay between glucose and lipid metabolism remain unclear. Various hormones, including sex hormones, can affect glucose metabolism in Sertoli cells by endocrine regulation. The activation or inhibition of signaling pathways such as AMPK, mTOR, and Akt can alter the expression levels of glycolysis-related transporter genes and the synthesis of fatty acids, thereby affecting glycolipid metabolism in Sertoli cells. Some transcription factors such as PPARγ can regulate downstream fatty acid metabolism-related genes by directly binding to their response elements and promoting the oxidation of fatty acids in Sertoli cells. In this article we elaborate on the key factors influencing glycolipid metabolism in Sertoli cells and their interconnections, as well as their potential clinical implications, offering new insights for precisely targeted treatments of male infertility.
Sertoli Cells/cytology* ; Male ; Glycolipids/metabolism* ; Spermatogenesis/physiology* ; Humans ; Lipid Metabolism ; Animals ; Fatty Acids/metabolism* ; Signal Transduction ; Glycolysis

Retinopathy of prematurity (ROP) is a proliferative retinal vascular disease that threatens the vision of premature infants. Various novel drugs have demonstrated therapeutic potential for ROP by targeting signaling pathways associated with vascular endothelial growth factor (VEGF) [such as PI3K/AKT, hypoxia-inducible factor (HIF)-1α/VEGF], oxidative stress, tumor necrosis factor (TNF)-α, and Notch pathways. Propranolol, insulin-like growth factor-1, and celecoxib attenuate pathological neovascularization via the PI3K/Akt signaling pathway. Tripterine and melatonin inhibit retinal neovascularization by modulating the HIF-1α/VEGF signaling axis. Adiponectin mitigates the damage caused by oxidative stress and preserves endothelial function by enhancing endothelial nitric oxide synthase activity. Omega-3 polyunsaturated fatty acids suppress TNF-α-mediated inflammatory responses, modulate retinal development and angiogenesis, and reduce retinal neovascular lesions. DAPT, a γ-secretase inhibitor, blocks Notch signaling to suppress abnormal vascular proliferation. These agents exhibit synergistic multi-pathway anti-angiogenic effects in preclinical models and early-phase clinical trials, offering critical insights for advancing drug development and clinical translation in ROP management.
Retinopathy of Prematurity/metabolism* ; Humans ; Signal Transduction/drug effects* ; Infant, Newborn ; Vascular Endothelial Growth Factor A/metabolism* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Oxidative Stress/drug effects* ; Fatty Acids, Omega-3/therapeutic use* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Receptors, Notch/metabolism* ; Angiogenesis Inhibitors/therapeutic use* ; Insulin-Like Growth Factor I/therapeutic use*

Messenger RNA (mRNA) therapeutics involve delivering in vitro transcribed mRNA into specific cells to produce target proteins for the treatment or prevention of diseases. However, the development of mRNA therapeutics relies largely on mRNA delivery systems. Lipid nanoparticles (LNPs) represent the most widely used mRNA carriers in clinical applications. Composed of ionizable lipids, zwitterionic phospholipids, cholesterol, and polyethylene glycol-lipids, LNPs can address critical challenges in mRNA drug development, such as poor in vivo stability and the difficulty in crossing biological barriers. Ultimately, LNPs enable safe, efficient, and targeted mRNA delivery to the liver, lung, spleen, and other organs. This review outlines the roles of the four lipid components in LNPs for mRNA delivery. It then introduces targeted mRNA delivery to various organs/tissues such as the liver, lung, spleen, pancreas, bone marrow, and placenta, using strategies such as antibody modification, lipid structure alteration, and specialized administration routes. Additionally, this review discusses the applications and challenges of LNP-based mRNA therapeutics in disease treatment, aiming to provide insights for the clinical translation of mRNA therapies and for further innovations in LNP delivery systems.
Humans ; RNA, Messenger/administration & dosage* ; Nanoparticles/chemistry* ; Lipids/chemistry* ; Drug Delivery Systems ; Animals ; Liposomes

Ferroptosis, a regulated cell death process distinct from apoptosis, is characterized by iron dysregulation and reactive oxygen species (ROS) accumulation. After intracerebral hemorrhage (ICH), decreased cerebral blood flow and iron released from erythrocytes trigger lipid peroxidation-particularly of polyunsaturated fatty acids (PUFAs)-through a cascade of reactions in local brain tissues, promoting ferroptosis. Mitochondrial dysfunction and neuroinflammation further elevate ROS, exacerbating lipid peroxidation and accelerating neuronal ferroptosis. Thus, PUFA peroxidation and associated metabolic pathways play a critical role in ICH-related neuronal damage. This review summarizes current understanding of how PUFA peroxidation contributes to ferro-ptosis after ICH, discusses key regulatory mechanisms involving lipid and iron metabolism, and highlights potential therapeutic strategies targeting ferroptosis to improve neurological outcomes.
Ferroptosis/physiology* ; Humans ; Cerebral Hemorrhage/pathology* ; Lipid Peroxidation ; Fatty Acids, Unsaturated/metabolism* ; Reactive Oxygen Species/metabolism* ; Iron/metabolism* ; Animals ; Mitochondria/metabolism*

OBJECTIVE: To compare the lipid metabolites in the seminal plasma of normal fertile men from those of the patients with oligoasthenoteratozoospermia (OAT), and perform a pathway enrichment analysis on the differentially expressed lipids. METHODS: According to strict inclusion and exclusion criteria, we recruited 30 males seeking medical attention in our Center of Reproductive Medicine and equally divided them into an OAT and a normal fertile control group. Employing the untargeted metabolomics approach, we screened the differential lipids in the seminal plasma of the OAT patients and subjected them to pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. RESULTS: In the OAT patients, the expressions of 22 lipids were significantly upregulated and those of 32 downregulated in the positive ion mode, and the expressions of 2 lipids upregulated and those of 12 downregulated in the negative ion mode. And 5 of the significantly downregulated lipids, namely anandamide(20:4,n-6), adrenic acid, cis-gondoic acid, (3'-sulfo)galbeta-cer(d18:1/24:1(15Z)) and palmitoylcarnitine, were associated with 4 branches and 8 sub-branches of the KEGG metabolic pathways, among which the differential lipid anandamide (20:4,n-6) was involved in the regeneration of the biological system in the KEGG sub-pathway and considered to be a significantly differentially enriched pathway. CONCLUSION Lipid metabolites in the seminal plasma of OAT patients are significantly different from those in normal fertile males, and the differential lipid anandamide (20:4,n-6) may be involved in the regulation of sperm function and play an important role in male fertility.
Humans ; Male ; Semen/metabolism* ; Adult ; Lipids/analysis* ; Case-Control Studies ; Asthenozoospermia/metabolism* ; Oligospermia/metabolism* ; Lipid Metabolism ; Mass Spectrometry