Background: When the deer antler is cast, it leaves a cutaneous wound that can achieve scarless healing due to the presence of antler stem cells (ASCs). This provides an opportunity to study regenerative wound healing. Methods: In this study, we investigated the therapeutic effects and mechanism of antler stem cell-conditioned medium (ASC-CM) on cutaneous wound healing in rats. In vitro, we investigated the effects of the ASC-CM on proliferation of HUVEC and NIH-3T3 cell lines. In vivo, we evaluated the effects of ASC-CM on cutaneous wound healing using full-thickness skin punch-cut wounds in rats. Results: The results showed that ASC-CM significantly stimulated proliferation of the HUVEC and NIH-3T3 cells in vitro. In vivo, completion of healing of the rat wounds treated with ASC-CM was on day 16 (± 3 days), 9 days (± 2 days) earlier than the control group (DMEM); the area of the wounds treated with ASC-CM was significantly smaller (p < 0.05) than the two control groups. Further molecular characterization showed that the ratios of Col3A1/Col1A2, TGF-β3/TGF-β1, MMP1/TIMP1, and MMP3/TIMP1 significantly increased (p < 0.01) in the healed tissue in the ASC-CM group. Conclusions: In conclusion, ASC-CM effectively accelerated the wound closure rate and enhanced the quality of healing, which might be through transforming wound dermal fibroblasts into the fetal counterparts. Therefore, the ASC-CM may have potential to be developed as a novel cell-free therapeutic for scarless wound healing.

Deer antlers are organs of bone and have an extremely rapid growth rate. Thus far, the molecular mechanism underlying rapid antler growth has not been properly elucidated, and key genes driving this growth rate have not been fully identified. In this study, based on the newly assembled high-quality sika deer genome, we conducted an integrated analysis of genome-wide association analysis (GWAS) and weighted gene co-expression network analysis (WGCNA) using genome resequencing data from our previous GWAS, with weight and transcriptome sequencing data of faster- vs. slower-growing antlers of sika deer. The expressions of key genes were verified using Fragments Per Kilobase of transcript per Million fragments mapped (FPKM) in different tissue zones of the antler growth center, different types of sika deer tissues and antler tissues collected from faster and slower growth rates. The results show that a total of 49 genes related to antler growth rate were identified, and most of those genes were enriched in the IGF1R and LOX modules. The gene regulation network of antler growth rate through the IGF1R pathway was constructed. In conclusion, the integration of GWAS and WGCNA analyses had great advantages in identifying regulatory genes of complex antler growth traits over using singular methods individually, and we believe that our findings in the present study can provide further insight into unveiling the mechanism underlying extraordinary fast antler growth rate in particular, as well as the regulatory mechanism of rapid tissue proliferation in general.

Due to the limited supply of autologous bone grafts, there is a need to develop more bone matrix materials to repair bone defects. Xenograft bone is expected to be used for clinical treatment due to its exact structural similarity to natural bone and its high biocompatibility. In this study, decellularized antler cancellous bone matrix (DACB) was first prepared, and then the extent of decellularization of DACB was verified by histological staining, which demonstrated that it retained the extracellular matrix (ECM). The bioactivity of DACB was assessed using C3H10T1/2 cells, revealing that DACB enhanced cell proliferation and facilitated cell adhesion and osteogenic differentiation. When evaluated by implanting DACB into nude mice, there were no signs of necrosis or inflammation in the epidermal tissues. The bone repair effect of DACB was verified in vivo using sika deer during the antler growth period as an animal model, and the molecular mechanisms of bone repair were further evaluated by transcriptomic analysis of the regenerated tissues. Our findings suggest that the low immunogenicity of DACB enhances the production of bone extracellular matrix components, leading to effective osseointegration between bone and DACB. This study provides a new reference for solving bone defects.

Background: Myelosuppression is one of the most common chemotherapy side effects, seriously threatening the quality of life of cancer patients. Studies have shown that velvet antler polypeptides (VAPs) could enhance immunity and anti-aging and also have a hematopoietic-promoting effect. However, there are relatively few studies on the treatment of myelosuppression with VAPs, and the therapeutic mechanism remains unclear. Methods: This study employed both in vitro and in vivo models to explore the mechanism of VAPs against myelosuppression. In this study, the cyclophosphamide (CTX)-induced bone marrow mesenchymal stem cell (BMSC) injury model was used to evaluate the effects of VAPs on cell viability, apoptosis, reactive oxygen species activity, and protein expression. Furthermore, a CTX-induced myelosuppression mouse model was employed to evaluate peripheral blood counts, organ indices, femoral tissue histopathology, immunohistochemical expression of CD34, VEGF, and Notch1, and key proteins in the Notch1/PI3K/AKT pathway in vivo. Results: Our results showed that VAPs protected BMSCs from CTX-induced apoptosis, inhibited ROS production, and promoted the secretion of VEGF, TPO, and VCAM-1, thereby improving the bone marrow microenvironment. Furthermore, the results showed that VAPs improved the peripheral blood counts and bone marrow nucleated cell (BMNC) count in CTX-induced myelosuppression mice and ameliorated pathological injury of the spleen, thymus, and liver. VAPs inhibited the apoptosis of bone marrow cells, manifested by regulating the expression levels of proteins like PI3K/p-PI3K, AKT/p-AKT, Bcl-2, Bax, and Caspase-3. Simultaneously, it upregulated the expression of Notch1 and Hes1 proteins. The application of the PI3K inhibitor LY294002 and the Notch1 inhibitor DAPT demonstrated that the ameliorative effect of VAPs on myelosuppression was dependent on the activation of both the Notch1 and PI3K/AKT pathways. Conclusions: Our study indicates that VAPs may achieve treatment of myelosuppression by improving the hematopoietic microenvironment, inhibiting apoptosis of mouse bone marrow cells, and regulating the Notch1 and PI3K/AKT signaling pathways.

The molecular mechanism underlying rapid antler growth has not been elucidated. The contrast of the wapiti and sika deer antler provides a potential model for comparative studies for the identification of potent growth factors and unique regulatory systems. In the present study, reference transcriptomes of antler RM tissue of wapiti and sika deer were constructed using single molecule real time sequencing data. The expression profiling, positive selection, and alternative splicing of the antler transcripts were compared. The results showed that: a total of 44,485 reference full-length transcripts of antlers were obtained; 254 highly expressed transcripts (HETs) and 1936 differentially expressed genes (DEGs) were enriched and correlated principally with translation, endochondral ossification and ribosome; 228 genes were found to be under strong positive selection and would thus be important for the evolution of wapiti and sika deer; among the alternative splicing variants, 381 genes were annotated; and 4 genes with node degree values greater than 50 were identified through interaction network analysis. We identified a negative and a positive regulator for rapid antler growth, namely RNA Binding Motif Protein X-Linked (RBMX) and methyltransferase-like 3 (METTL3), respectively. Overall, we took advantage of this significant difference in growth rate and performed the comparative analyses of the antlers to identify key specific factors that might be candidates for the positive or negative regulation of phenomenal antler growth rate.

The blood–brain barrier (BBB) presents the principal obstacle to drug delivery for Alzheimer’s disease (AD), severely restricting brain bioavailability and therapeutic efficacy. Taxifolin (TF) is a potent natural antioxidant with significant therapeutic potential. To enhance its efficacy in treating AD, we developed a brain-targeted delivery system based on a taxifolin-loaded thermosensitive hydrogel (TF-Gel). This platform integrates TF with a poly(N-isopropylacrylamide)-based thermosensitive hydrogel to enhance brain delivery, tissue penetration, and intracerebral retention via intranasal administration. TF-Gel exhibits excellent structural stability and functional performance, enabling efficient bypass of the BBB through the nasal–brain pathway. Furthermore, it regulates mitochondrial dysfunction, reverses abnormal levels of adenosine triphosphate (ATP), reactive oxygen species (ROS), and malondialdehyde (MDA) in neuronal mitochondria, repairs mitochondrial energy metabolism, restores mitochondrial dynamic balance, improves oxidative stress damage, and blocks cell apoptosis pathways. Collectively, these results highlight the strong potential of the TF-Gel nasal delivery system as a mitochondria-targeted therapeutic strategy for AD.