Lijun Hao

Lipid droplet (LD) accumulation and impaired lipid mobilization induce lipotoxic stress and contribute to metabolic, cardiovascular, cancer, and neurodegenerative diseases (NDDs). Although LD-selective autophagy (lipophagy) is being increasingly studied, the mechanisms that confer LD specificity and enable tissue- and stage-specific therapeutic modulation remain unclear. Effective lipophagic flux requires coordinated LD coat remodeling, nutrient and energy sensing, and organelle contact. Coat remodeling governs substrate access and droplet recognition. The AMPK-mTORC1-TFEB axis links autophagy induction to lysosome biogenesis and capacity. Endoplasmic reticulum (ER)-LD, mitochondria-LD, and LD-lysosome contact sites facilitate lipid transfer by coupling lysosomal hydrolysis to mitochondrial β-oxidation. Lipophagy is a highly stage- and cell-type-dependent process: it removes excess lipids to protect cells, but its dysregulation can promote inflammation and fibrogenesis or supply substrates to tumors. This review synthesizes mechanistic and translational evidence on lipophagy initiation, regulation, and disease relevance, and identifies the following priorities: robust biomarkers, distinction of cargo-recognition defects from lysosomal dysfunction, and precision interventions tailored to the tissue and disease stage.

A correction refers to a change to their article that the author wishes to publish after publication. The publication of this article is subject to Frontiers' editorial approval. Instructions: ● Please read through all the templates before choosing ● Pick the most relevant text template(s) from the following page and delete all others. ● Edit the text as necessary, ensuring that the original incorrect text is included for the record, please see the below. ● Please do not use any extra formatting when editing the templates, and only modify the red text unless absolutely necessary ● Submit to Frontiers following the instructions on this page. When the original text contained incorrect information, to preserve the scientific record, please include that text when editing the below templates. For example: There was a mistake in the Funding statement, an incorrect number was used. The correct number is "2015C03Bd051.". The publisher apologizes for this mistake. The original version of this article has been updated. In the published article, there was a mistake in the Funding statement. The funding statement for the Key Development Project of the Department of Science and Technology was displayed as "2015CBd051". The correct statement is "Key Development Project of Department of Science and Technology (2015C03Bd051).''

Background: Acute radiation-induced dermatitis refers to skin lesions that usually appear within 90 days of the start of radiotherapy. Although various treatments are available, none have proven fully effective. Exosomes produced by adipose-derived stem cells play crucial roles in enhancing cell regeneration, promoting angiogenesis, regulating inflammation and remodeling the extracellular matrix. Hyaluronic acid, a major extracellular matrix component, is synthesized by hyaluronic acid synthase, with hyaluronic acid synthase 1 being particularly critical for skin repair. This study aimed to investigate whether exosomes derived from adipose-derived stem cells can protect against radiation-induced acute skin damage and to elucidate the underlying mechanisms involving hyaluronic acid synthase 1. Methods: Thirty-six male adult SD rats were randomly divided into a negative control group, an irradiation group (90 Gy), and a radiation + exosomes group (90 Gy + 100 ug exosomes). Three groups of fibroblasts were assigned: one for control, one for radiation (6 Gy), and one for radiation plus exosomes (6 Gy + 4 ug exosomes). The effect of ADSC-exos transplantation was evaluated using skin damage score, histopathological analysis, electron microscopy, immunohistochemical staining, immunofluorescence staining, and immunoblotting analysis. Furthermore, small interfering RNA-mediated knockdown of hyaluronic acid synthase 1 was performed to explore its regulatory role in the TGF-β/Smad2/3 signaling pathway. Results: After irradiation, the ADSC-exos intervention significantly increased the levels of stromal cell-derived factor-1, matrix metalloproteinases, transforming growth factor, basic fibroblast growth factor, platelet-derived growth factor, vascular endothelial growth factor, interleukin 10, interleukin 12, and reduced the expression of the pro-inflammatory factor interleukin 6. Notably, exosomes treatment markedly upregulated hyaluronic acid synthase 1 expression, and small interfering RNA-mediated knockdown of hyaluronic acid synthase 1 resulted in reduced phosphorylation of TGF-β/Smad2/3 signaling components, indicating that hyaluronic acid synthase 1 is a critical mediator of this pathway. Conclusion: Exosomes derived from adipose-derived stem cells alleviate acute radiation-induced dermatitis by enhancing hyaluronic acid synthase 1 expression and activating the TGF-β/Smad2/3 pathway, thereby promoting skin regeneration and repair. These findings suggest that exosomes derived from adipose-derived stem cells may serve as a promising cell-free therapeutic strategy for the prevention and treatment of acute radiation-induced dermatitis. Graphical

Background Nostril overexposure is a common aesthetic concern among Asian populations, which significantly affects facial harmony. Traditional surgical interventions carry risks such as substantial trauma and visible scarring. This study aims to evaluate the clinical efficacy of Botulinum Toxin Type A (BoNT-A) injections in treating nostril overexposure using three-dimensional (3D) scanning technology. Methods This study recruited 52 patients seeking improvement for nostril overexposure. BoNT-A was injected into the nasal dilator muscles. Changes in nostril cross-sectional area and alar mobility were quantified using 3D scanning technology before treatment and at 4, 12, and 24 weeks post-treatment. Subjective improvements were evaluated by patients and one independent plastic surgery experts using the Global Aesthetic Improvement Scale (GAIS). Results A total of 32 patients completed the entire 24-week follow-up period. Post-treatment 3D analysis showed a significant reduction in both nostril cross-sectional area and alar mobility. At 4 weeks post-injection, the nostril area decreased from 89.42 ± 13.21 to 72.50 ± 13.93 mm² (p < 0.05), and alar mobility decreased from 10.50 ± 3.92 to 4.64 ± 3.09% (p < 0.05). GAIS scores indicated that both patients and expert rated the improvement as significant at 4 weeks. Measurements at 24 weeks approached baseline levels. Conclusion BoNT-A injections effectively and safely improve nostril overexposure with high patient satisfaction. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Background: Lip augmentation has become increasingly accepted and popular. However, there are still a few approved lip fillers that are versatile, biocompatible, suitable for lip enhancement, and backed by large-scale clinical trials. Objectives: To assess the safety and effectiveness of Janlane LIPs (Shanghai Qisheng Biopharmaceutical Co., Ltd, Shanghai, China), a new hyaluronic acid filler for lip augmentation. Methods: This prospective, multicenter, randomized, controlled study randomized subjects to the treatment group or the concurrent no-treatment control group that received delayed treatment. The level of Lip Fullness Grading Scale (LFS) was evaluated by the blinded evaluator, and the Global Aesthetic Improvement Scale (GAIS) was evaluated by the blinded evaluator and the subjects at pre-injection and after injection. Adverse reactions were recorded. Statistical analysis of subject satisfaction was performed. Results: A total of 176 subjects were enrolled. The scores of LFS after injection were higher than those before injection; the degree of GAIS evaluated by the evaluator and subjects improved significantly. Local redness, swelling, etc. occurred after injection, most of which resolved within 1 week. The patient satisfaction was high and statistically significant. Conclusions: Janlane LIPs showed long-term aesthetic improvement and safety for lip augmentation, high patient satisfaction, and are worthy of clinical promotion. Level of Evidence: 2 (Therapeutic):

Background Some facial morphological changes may occur in some patients after botulinum toxin A (BTX-A) injection for the treatment of masseteric hypertrophy. The aim of this study was to investigate the morphological changes that occurred on mandibular margin. Methods This retrospective analysis included 43 patients (86 lateral cases) who received BTX-A injections for masseter hypertrophy. To assess the morphological changes in the mandibular margin after treatment, the sharpness of the mandibular margin was evaluated before and after the injections using an established grading system. Additionally, 3D scanning technology was used to measure both the therapeutic effect of the BTX-A injections and the extent of soft tissue sagging in the mandibular margin area. Results Grading: The grade of mandibular margin sharpness change occurred in 41 lateral cases post-procedurally. Evaluation: Based on the measurement results, statistically significant differences were observed before, 1 month, and 3 months post-procedurally in subjects’ positive lower face width representing the therapeutic effect of BTX-A injection and the extent of sagging soft tissue at sagittal section B and section C (p < 0.05), but not in section A (A: outer canthus, B: midpoint of the eyelid margin, and C: inner canthus) (p > 0.05). Conclusion After receiving a BTX-A injection for masseteric hypertrophy, the mandibular margin may develop an unclear mandibular margin and sagging soft tissue in mandibular margin area. EBM Level: IV Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Background: Keloid is a fibroproliferative disease with unsatisfactory therapeutic effects and a high recurrence rate. exosomes produced by adipose-derived mesenchymal stem cells (ADSC-Exos) have attracted significant interest due to their ability to treat fibrosis. However, the molecular mechanisms of ADSC-Exos in keloids remain inconclusive. Objective: Our study revealed the relationship between ferroptosis and fibrosis in keloids. Subsequently, this study aimed to explore further the anti-fibrotic effect of ADSC-Exos on keloids through ferroptosis and the potential underlying mechanisms. Methods: To investigate the impact of ferroptosis on keloid fibrosis, Erastin and ferrostatin-1 (fer-1) were utilized to treat keloid fibroblast. Keloid keloids treated with Erastin and fer-1 were cocultured with ADSC-Exos to validate the impact of ferroptosis on the effect of ADSC-Exos on keloid anti-ferrotic protein, peroxidase 4 (GPX4) and anti-fibrotic effects in vivo and in vitro by Western blot, as well as variations in iron metabolite expression, malondialdehyde (MDA), liposomal peroxidation (LPO) and glutathione (GSH) were analyzed. The effect of solute carrier family 7-member 11 (SLC7A11) silencing on ADSC-Exo-treated keloid fibroblast was investigated. Results: Iron metabolite dysregulation was validated in keloids. Fibrosis progression is enhanced by Erastin-induced ferroptosis. The anti-fibrotic effects of ADSC-Exos and fer-1 are related to their ability to prevent iron metabolism. ADSC-Exos effectively suppressed keloid fibrosis progression and increased GSH and GPX4 gene expression. Additionally, the use of Erastin limits the effect of ADSC-Exos in keloids. Furthermore, the effect of ADSC-Exos on keloids was associated with SLC7A11-GPX4 signaling pathway. Conclusion: We demonstrated a new potential mechanism by which anti-ferroptosis inhibits the progression of keloid fibrosis and identified an ADSC-Exo-based keloid therapeutic strategy. Resisting the occurrence of ferroptosis and the existence of the SLC7A11-GPX4 signaling pathway might serve as a target for ADSC-Exos.

Background: Macrophage-mediated inflammatory response in the early post-grafting period restricts fat graft retention. Pyroptosis is a novel type of programmed cell death that extensively participates in inflammatory pathologies. Objectives: This study sought to determine whether macrophage pyroptosis was activated during the inflammatory phase after fat grafting and to investigate the efficacy of a pyroptosis inhibitor, disulfiram (DSF), in fat graft retention. Methods: We established a C57BL/6 mice fat grafting model and then analyzed macrophage pyroptosis. DSF (50 mg/kg, every other day) was intraperitoneally injected starting 1 hour before fat grafting and continued for 14 days. An in vitro co-culture system was established in which mouse RAW264.7 macrophages were co-cultured with apoptotic adipocytes to further validate the findings of the in vivo studies and to explore the underlying mechanisms. Results: Here we reported that macrophage pyroptosis was activated in both fat grafts and in vitro co-culture models. DSF was found to be a potent pyroptosis inhibitor, promoting M2 macrophage polarization. In addition, DSF was demonstrated to enhance vascularization and graft retention. Conclusions: Our results suggested that pyroptosis plays a crucial role in the inflammatory cascade within fat grafts. DSF, being a clinically available drug, could be translated into a clinically effective drug for improving fat graft survival by inhibiting macrophage pyroptosis, therefore inducing M2 macrophage polarization and promoting neovascularization.

Keloid is a fibroproliferative disease of unknown aetiology, which has a significant impact the quality of life of patients. Ferroptosis plays an important role in the occurrence and development of fibrosis, but there is still a lack of research related to keloids. The objective of this work was to identify the hub genes related to ferroptosis in keloid to better understand the keloid process. The microarray data (GSE7890 GSE145725, and GSE44270) (23 keloid and 22 normal fibroblast) were analysed via the gene expression comprehensive database (GEO). Only GSE7890 met the FerrDB database. Cell cycle and pathway analysis were performed with gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed to differentially expressed genes (DEG). The differential genes were confirmed in other GEO datasets (GSE145725 and GSE44270), and multi‐fibrosis‐gene correlation analysed. To validate these hub genes, quantitative real‐time PCR (qRT‐PCR) was conducted. A total of 581 DEGs were screened, with 417 genes down‐regulated and 164 genes up‐regulated, with 11 ferroptosis genes significantly up‐regulated in both keloid and normal tissue, and 6 genes are consistent with our findings and are associated with multiple fibrosis genes. The qRT‐PCR results and tissues of normal skin and keloid agreed with our predictions. Our findings provide new evidence for the ferroptosis‐related molecular pathways and biomarker of keloid.