Impaired angiogenesis and bacterial infection have increasingly been implicated as the major causes of delayed diabetic wound healing. However, there is currently no effective therapy. Here, we optimized a novel gene delivery system based on antimicrobial peptide (LL37) grafted ultra-small gold nanoparticles (AuNPs@LL37, ∼7 nm) for the topical treatment of diabetic wounds with or without bacterial infection. AuNPs@LL37 combines the advantages of cationic AuNPs that condense DNA with those of antibacterial peptides, which are both highly antibacterial and essential for enhancing cellular and nucleus entry to achieve high gene delivery efficiency. AuNPs@LL37 combined with pro-angiogenic (VEGF) plasmids (AuNPs@LL37/pDNAs) significantly improved the gene transfection efficiency in keratinocytes compared with pristine AuNPs/pDNAs, and showed similar expression to Lipo2000/pDNAs (a well-known highly efficient gene transfection agent). Moreover, our therapeutic depot showed higher antibacterial ability than the free antimicrobial peptides and the cationic AuNPs alone in vitro and in vivo due to synergistic effects. Furthermore, the combined system promoted angiogenesis and inhibited bacterial infection in diabetic wounds, resulting in accelerated wound closure rates, faster re-epithelization, improved granulation tissue formation and high VEGF expression. Finally, our therapeutic depot was highly biocompatible in vitro and in vivo, suggesting its potential as a feasible way to treat chronic diabetic wounds.

Hypertrophic scar (HS), a fibroproliferative disorder caused by aberrant wound healing following skin injuries such as burns, lacerations and surgery, is characterized by invasive proliferation of fibroblasts and excessive extracellular matrix (ECM) accumulation. The dysregulation of autophagy is the pathological basis of HS formation. Previously, angiopoietin-2 (ANGPT2) was found to be overexpressed in HS fibroblasts (HSFs) compared with normal skin fibroblasts. However, whether ANGPT2 participates in the process of HS formation and the potential molecular mechanisms are not clear. This study is intended to figure out the role of ANGPT2 and ANGPT2-mediated autophagy during the development of HS. RT-qPCR was used to detect ANGPT2 expression in HS tissues and HSFs. HSFs were transfected with sh-ANGPT2 to knock down ANGPT2 expression and then treated with MHT1485, the mTOR agonist. The effects of sh-ANGPT2 or MHT1485 on the proliferation, migration, autophagy and ECM accumulation of HSFs were evaluated by CCK-8 assay, Transwell assay and western blotting. The expression of PI3K/Akt/mTOR pathway-related molecules (p-PI3K, p-Akt and p-mTOR) was assessed by western blotting. ANGPT2 expression was markedly upregulated in HS tissues and HSFs. ANGPT2 knockdown decreased the expression of p-PI3K, p-Akt and p-mTOR. ANGPT2 knockdown activated autophagy and inhibited the proliferation, migration, and ECM accumulation of HSFs. Additionally, the treatment of MHT1485, the mTOR agonist, on ANGPT2-downregulated HSFs, partially reversed the influence of ANGPT2 knockdown on HSFs. The study lacks the establishment of more stable in vivo animal models of HS for investigating the effects of ANGPT2 on HS formation in experimental animals. ANGPT2 downregulation represses growth, migration, and ECM accumulation of HSFs via autophagy activation by suppressing the PI3K/Akt/mTOR pathway. Our study provides a novel potential therapeutic target for HS.

Background: Hypertrophic scars (HTSs) are a predominant condition after burns and trauma, and it causes severe physiological and psychological problems. TikTok (Douyin in Chinese), a popular platform for sharing short videos, has shown the potential to spread health information, including information related to HTSs. Educating the public to obtain correct information is important to reduce the incidence of physiological and psychological problems caused by HTSs. However, the quality and reliability of HTS-related video content on TikTok in mainland China have not been thoroughly studied. Objective: This study aims to evaluate the content and quality of short videos related to HTSs on the Chinese version of TikTok (Douyin) and explore the factors related to their quality, providing valuable insights for health information dissemination. Methods: We collected a sample of 153 TikTok videos in Chinese related to HTSs and categorized them according to video source and content. We evaluated the video content using a coding schema, and a hexagonal radar schema was used to intuitively display the spotlight and weight of each aspect of the videos. We evaluated quality using 4 standardized tools: the modified DISCERN (mDISCERN) questionnaire, the Journal of the American Medical Association, the Global Quality Scale (GQS), and the Health on the Net Foundation Code of Conduct. We also explored the potential relationship between video quality and characteristics. Results: The analysis showed that health care professionals uploaded all videos about treating HTSs, which matched the hexagonal radar model analysis findings. The quality assessment scores for the Journal of the American Medical Association, GQS, mDISCERN, and the Health on the Net Foundation Code of Conduct had median values of 1 (IQR 1-2), 2 (IQR 2-3), 2 (IQR 2-3), and 3 (IQR 3-4), respectively, indicating a need to improve the quality and reliability of videos on HTSs. In addition, high-quality videos were more popular, based on metrics such as likes, comments, favorites, and shares (P<.001). Interestingly, the time when the videos were uploaded positively correlated with GQS and mDISCERN scores (r=0.393; P<.001 and r=0.273; P<.001), while the video length did not significantly correlate with evaluation scores (P=.78, P=.20, P=.07, and P=.04). Conclusions: The quality of TikTok videos related to HTSs is generally moderate. Users should exercise caution when seeking information on HTSs from TikTok. It is advisable to choose videos uploaded by health care professionals from the burn department and the burn plastic surgery department, and in the Chinese context, those produced in first-tier cities and emerging first-tier cities.

1α,25-Dihydroxyvitamin D3 (VD3), the active form of vitamin D, plays a crucial role in wound healing. In this study, we aimed to investigate the effect of VD3 on the proliferation and differentiation of epidermal stem cells (EpSCs) and monitor its impact on re-epithelialization. We established a murine full-thickness skin defect model and applied four doses of VD3 (0, 5, 50, and 250 ng/mouse/day) to the wounds topically for three days. Immunostaining and flow cytometry confirmed the effect of VD3 on the proliferation and differentiation of EpSCs in wounds. This effect of VD3 (0, 1, 10, and 50 nM) on EpSCs and its possible mechanism were further confirmed in vitro by CCK8, westen blot, immunostaining, and flow cytometry. We found that on day five post-wounding, the means±SD length of the neo-epidermis was 195.88±11.57, 231.84±16.45, 385.80±17.50, and 268.00±8.22 μm in the control, 5, 50, and 250 ng groups, respectively, with a significant difference from the control (all P<0.05). Immunostaining and flow cytometry showed that VD3 improved the proliferation and differentiation of K15+ EpSC (vs control, all P<0.05), K14+ epidermal progenitor cells (vs control, all P<0.05), and K10+ epidermal terminal cells (vs control, all P<0.05) in vivo and in vitro. The PI3K signaling pathway appeared to underlie this response because significant inhibition of the response was found when inhibitors were used to inhibit PI3K. Our study demonstrated that VD3 is a potent promoter of cutaneous wound healing by stimulating EpSC proliferation and differentiation through PI3K activation.

Background: The early inflammatory phase (EIP, 0–72 h) post-acute myocardial infarction (AMI) is a critical determinant of cardiac repair and clinical outcomes. However, a comprehensive understanding of the regulatory gene networks and cellular interactions that govern this decisive period remains incomplete. This study aimed to define the key transcriptional programs and immune dynamics during the EIP of AMI. Methods: We performed an integrated analysis of time-series bulk RNA-sequencing (RNA-seq) datasets (GSE206281, GSE153494) from murine myocardium post-ischemia. Single-cell RNA-seq (scRNA-seq) data (GSE163129, GSE163465) from cardiac immune cells were analyzed to characterize cellular heterogeneity and intercellular communication. A multi-modal framework combining inflammatory progression scoring with weighted gene co-expression network analysis (WGCNA) was applied to identify critical modules. Hub genes were pinpointed through protein-protein interaction network analysis and intersection with inflammation-related genes (IRGs). Their association with immune infiltration was assessed, and expression was validated in an external dataset, a murine AMI model, and a human peripheral blood cohort (GSE60993). Results: Temporal analysis identified 160 dynamically regulated genes post-AMI, prominently enriched in myeloid leukocyte activation and extracellular matrix organization. scRNA-seq revealed a remodeled immune landscape at day 3, characterized by increased proportions of macrophages, monocytes, and neutrophils, alongside enhanced intercellular signaling via pathways such as MIF and GALECTIN. Network analysis distilled a core set of seven inflammation-associated hub genes ( Grn , Igf1 , Il18 , Itgb2 , Ncf2 , Ncf4 , Spp1 ). These genes showed cell-type-specific expression patterns in myeloid subsets, correlated positively with myeloid cell infiltration in bulk tissue, and were significantly upregulated in the murine AMI model. Exploratory single-gene ROC analyses in a human peripheral blood cohort suggested preliminary differential expression trends for some hub genes (e.g., Spp1, Ncf4), but the very limited sample size precluded reliable construction of a multi-gene model and renders these findings strictly hypothesis-generating. Conclusions: This study delineates a high-resolution map of transcriptional and cellular dynamics during the EIP of AMI, revealing a coordinated network of inflammatory mediators linked to early myeloid cell recruitment and activation. The identified seven-candidate hub genes represents a prioritized set of candidates for future investigation into diagnostic biomarkers and therapeutic strategies targeting the early inflammatory window.

BACKGROUND Hypertrophic scars (HTSs) are a predominant condition after burns and trauma, and it causes severe physiological and psychological problems. TikTok (Douyin in Chinese), a popular platform for sharing short videos, has shown the potential to spread health information, including information related to HTSs. Educating the public to obtain correct information is important to reduce the incidence of physiological and psychological problems caused by HTSs. However, the quality and reliability of HTS-related video content on TikTok in mainland China have not been thoroughly studied. OBJECTIVE This study aims to evaluate the content and quality of short videos related to HTSs on the Chinese version of TikTok (Douyin) and explore the factors related to their quality, providing valuable insights for health information dissemination. METHODS We collected a sample of 153 TikTok videos in Chinese related to HTSs and categorized them according to video source and content. We evaluated the video content using a coding schema, and a hexagonal radar schema was used to intuitively display the spotlight and weight of each aspect of the videos. We evaluated quality using 4 standardized tools: the modified DISCERN (mDISCERN) questionnaire, the Journal of the American Medical Association, the Global Quality Scale (GQS), and the Health on the Net Foundation Code of Conduct. We also explored the potential relationship between video quality and characteristics. RESULTS The analysis showed that health care professionals uploaded all videos about treating HTSs, which matched the hexagonal radar model analysis findings. The quality assessment scores for the Journal of the American Medical Association, GQS, mDISCERN, and the Health on the Net Foundation Code of Conduct had median values of 1 (IQR 1-2), 2 (IQR 2-3), 2 (IQR 2-3), and 3 (IQR 3-4), respectively, indicating a need to improve the quality and reliability of videos on HTSs. In addition, high-quality videos were more popular, based on metrics such as likes, comments, favorites, and shares (P<.001). Interestingly, the time when the videos were uploaded positively correlated with GQS and mDISCERN scores (r=0.393; P<.001 and r=0.273; P<.001), while the video length did not significantly correlate with evaluation scores (P=.78, P=.20, P=.07, and P=.04). CONCLUSIONS The quality of TikTok videos related to HTSs is generally moderate. Users should exercise caution when seeking information on HTSs from TikTok. It is advisable to choose videos uploaded by health care professionals from the burn department and the burn plastic surgery department, and in the Chinese context, those produced in first-tier cities and emerging first-tier cities.