Improving depression-like behaviors caused by diabetes is likely to offer a new perspective for the treatment of non-healing chronic wounds.

Background: Three phases are often involved in the intricate process of wound healing: inflammatory exudation, cell proliferation, and tissue remodeling. It is challenging for wounds to heal if conditions like ischemia, persistent pressure, infection, repetitive trauma, or systemic or localized illnesses arise during the healing process. Chronic wounds are persistent injuries that do not follow the normal healing process and fail to progress through the stages of healing within a reasonable timeframe, like diabetic ulcers, vascular ulcers, pressure sores, and infectious wounds. Various factors affect chronic wound healing. A large body of research has illuminated that psychological distress may often be related to wound healing in clinical settings. Our observations have indicated that the pace of wound healing in diabetic mice is generally slower than that of healthy mice, and mice induced by streptozotocin (STZ) and fed a high-fat diet generally exhibit depression-like behavior. Our experiment delves into whether there is an inherent correlation and provides new ideas for clinical treatment to promote wound healing. Methods: In order to explore the relationship between diabetes, depression, and wound healing, we observed wound healing through HE staining, Masson's trichrome staining, and IHC staining for CD31 and detected the depressive condition through behavioral tests. Then, RT-PCR was used to detect the mRNA expression levels of α-SMA, Col1, CD31, and VEGF in wound tissue. Finally, the related brain areas were regulated through chemical genetic methods and the process of wound healing was observed. Conclusion: It has been observed that the lateral habenula (LHb) areas are associated with depression-like behavior induced by diabetes. Inhibiting LHb neuronal activity mitigates these depressive symptoms and enhances wound healing. Refractory wounds can be improved by considering patients' emotional issues from a broad standpoint, which provides fresh concepts for potential clinical treatments in the future.

Glutathione supplementation improves fat graft survival by inhibiting ferroptosis via the SLC7A11/GPX4 axis.

BACKGROUND: Autologous fat grafting is hampered by unpredictable graft survival, which is potentially regulated by ferroptosis. Glutathione (GSH), a powerful antioxidant used in tissue preservation, has ferroptosis-regulating activity; however, its effects on fat grafts are unclear. This study investigated the effects and mechanisms of GSH in fat graft survival. METHODS: Human lipoaspirates were transplanted subcutaneously into the backs of normal saline-treated (control) or GSH-treated nude mice. Graft survival was evaluated by magnetic resonance imaging and histology. RNA sequencing was performed to identify differentially expressed genes and enriched pathways. GSH activity was evaluated in vitro using an oxygen and glucose deprivation (OGD) model of adipose-derived stem cells. RESULTS: Compared with control group, GSH induced better outcomes, including superior graft retention, appearance, and histological structures. RNA sequencing suggested enhanced negative regulation of ferroptosis in the GSH-treated grafts, which showed reduced lipid peroxides, better mitochondrial ultrastructure, and SLC7A11/GPX4 axis activation. In vitro, OGD-induced ferroptosis was ameliorated by GSH, which restored cell proliferation, reduced oxidative stress, and upregulated ferroptosis defense factors. CONCLUSIONS: Our study confirms that ferroptosis participates in regulating fat graft survival and that GSH exerts a protective effect by inhibiting ferroptosis. GSH-assisted lipotransfer is a promising therapeutic strategy for future clinical application.

Single-cell RNA-seq and bulk-seq identify RAB17 as a potential regulator of angiogenesis by human dermal microvascular endothelial cells in diabetic foot ulcers.

Background: Angiogenesis is crucial in diabetic wound healing and is often impaired in diabetic foot ulcers (DFUs). Human dermal microvascular endothelial cells (HDMECs) are vital components in dermal angiogenesis; however, their functional and transcriptomic characteristics in DFU patients are not well understood. This study aimed to comprehensively analyse HDMECs from DFU patients and healthy controls and find the potential regulator of angiogenesis in DFUs. Methods: HDMECs were isolated from skin specimens of DFU patients and healthy controls via magnetic-activated cell sorting. The proliferation, migration and tube-formation abilities of the cells were then compared between the experimental groups. Both bulk RNA sequencing (bulk-seq) and single-cell RNA-seq (scRNA-seq) were used to identify RAB17 as a potential marker of angiogenesis, which was further confirmed via weighted gene co-expression network analysis (WGCNA) and least absolute shrink and selection operator (LASSO) regression. The role of RAB17 in angiogenesis was examined through in vitro and in vivo experiments. Results: The isolated HDMECs displayed typical markers of endothelial cells. HDMECs isolated from DFU patients showed considerably impaired tube formation, rather than proliferation or migration, compared to those from healthy controls. Gene set enrichment analysis (GSEA), fGSEA, and gene set variation analysis (GSVA) of bulk-seq and scRNA-seq indicated that angiogenesis was downregulated in DFU-HDMECs. LASSO regression identified two genes, RAB17 and CD200, as characteristic of DFU-HDMECs; additionally, the expression of RAB17 was found to be significantly reduced in DFU-HDMECs compared to that in the HDMECs of healthy controls. Overexpression of RAB17 was found to enhance angiogenesis, the expression of hypoxia inducible factor-1α and vascular endothelial growth factor A, and diabetic wound healing, partially through the mitogen-activated protein kinase/extracellular signal-regulated kinase signalling pathway. Conclusions: Our findings suggest that the impaired angiogenic capacity in DFUs may be related to the dysregulated expression of RAB17 in HDMECs. The identification of RAB17 as a potential molecular target provides a potential avenue for the treatment of impaired angiogenesis in DFUs.

Cyclic Diguanylate G-Quadruplex Inducer-Nitric Oxide Donor Conjugate as a Bifunctional Antibiofilm Agent and Antibacterial Synergist against Pseudomonas aeruginosa with a Hyperbiofilm Phenotype.

Antibiotic resistance caused by biofilm formation is a clinical challenge. Nitric oxide (NO) can effectively disperse a mature biofilm and can also synergistically influence the level of cyclic diguanylate (c-di-GMP), a universal secondary messenger that plays an important role in biofilm formation in bacteria. Based on our previous finding that c-di-GMP G-quadruplex inducers are effective biofilm formation inhibitors, we designed and synthesized a c-di-GMP G-quadruplex inducer-NO donor conjugate (A11@NO) as a bifunctional antibiofilm agent after obtaining the c-di-GMP G-quadruplex inducer (A11), which has an amino group capable of binding to a nitroso group (NO donor). The conjugate A11@NO showed better biofilm inhibition efficiency than A11, and it can also eradicate mature biofilm. Additionally, it exhibited good antimicrobial synergism against Pseudomonas aeruginosa and helped elevate the bactericidal efficiency of tobramycin against biofilm-formed bacteria. In combination with tobramycin, A11@NO also improved the survival rate of Caenorhabditis elegans in a hyperbiofilm environment.

Multiple system atrophy associated with Meige syndrome: A rare case report.

Multiple system atrophy (MSA) is a rare form of adult-onset α-synucleinopathy. Meige syndrome, identified as bilateral blepharospasm and oromandibular dystonia, is a type of focal dystonic movement disorder. This case report aims to highlight the clinical features of multiple system atrophy associated with Meige syndrome in a patient. Additionally, we aim to provide the treatment experience in a patient with Meige syndrome as this is an extremely rare clinical case.

The activation of FPR3/PKA/Rap1/ERK1/2 and FPR3/p-IκB/NF-κB axis in fibroblasts promote capsular contracture after rhinoplasty.

BACKGROUND: Capsular contracture may occur after rhinoplasty due to rejection of silicone implants by the immune system. Our previous high-throughput sequencing of RNA in nasal capsular contracture tissue revealed that FPR3 was significantly increased in grade IV capsular contracture tissue, compared with grade II. OBJECTIVE: This study aimed to elucidate the effect and specific mechanism of FPR3 on capsular formation and contracture following rhinoplasty. METHODS: Using the GeneMANIA Database, the genes involved with FPR3 expression were searched, and the Gene Ontology analysis was performed to annotate the biological functions of the aforementioned genes. The mRNA and protein expressions of related genes in fibroblasts and capsular contracture tissues were analyzed using quantitative real-time PCR, western blot, and immunohistochemical staining. CCK-8 was used to determine the viability of cells. The migration capacity of fibroblasts was assessed using a wound healing assay. ELISA was used to detect levels of IL-1ß, TNF-α, and IL-6. RESULTS: After rhinoplasty, the expression of FPR3 in the capsular tissue increased in proportion to the degree of contracture. By activating the PKA/Rap1/ERK1/2 axis, overexpression of FPR3 can significantly increase the cell viability of fibroblasts and promote their transformation into myofibroblasts. Moreover, FPR3 phosphorylates IκB to decrease NF-κB inhibition, thereby promoting the synthesis and release of the inflammatory cytokines IL-1ß, TNF-α, and IL-6. CONCLUSION: FPR3 is a crucial molecule that causes capsular development and contracture following rhinoplasty. In the future, local suppression of FPR3 may be an effective treatment for relieving capsular contracture.

Infectious shock after liposuction.

BACKGROUND: Liposuction has become one of the most popular cosmetic surgeries in China. However, few studies have discussed infectious shock caused by C. perfringens as one of the causes of death after liposuction. CASE PRESENTATION: A 24-year-old woman was brought to the emergency department (ED) of Guangzhou Chinese Overseas Hospital for treatment. The patient had undergone liposuction in her bilateral lower limbs two days prior. At the ED, the patient was unconscious, and had bilateral equal-sized (diameter, 6 mm) round pupils, no light reflex, a blood pressure (BP) of 71/33 mmHg, a heart rate of 133 bpm, and an SpO2 of 70%. She had bilateral limb swelling, extensive ecchymoses in her lower abdomen and bilateral thighs, local crepitus, blisters, weak pulses on her femoral artery and dorsalis pedis, high skin tension, and hemoglobin of 32 g/L. The patient was diagnosed with Clostridium perfringens infection, and she underwent debridement surgery and supportive treatment. But the patient's BP could not improve. At 8:28 pm on the day of admission, the patient was declared clinically dead after the electrocardiograph showed a horizontal line and spontaneous respiration ceased. CONCLUSIONS: Failure to meet surgical disinfection and environmental standards may be the cause of infection of C. perfringens through wounds. Therefore, it is necessary to strengthen the environmental disinfection of the operating room, and standardize the sterile conditions of the operation staff and patients before and during operation. Liposuction surgery necrotizing fasciitis is a rare but fatal complications, especially if diagnosis delay, therefore it is critical for early diagnosis and treatment of gas gangrene.

Comparative transcriptomics discloses the regulatory impact of carbon/nitrogen fermentation on the biosynthesis of Monascus kaoliang pigments.

Carbon and nitrogen play a fundamental role in the production of Monascus pigments. However, their effects on pigment biosynthesis remain undetermined. In this study, we found that Monascus kaoliang produces pigments via liquid fermentation using glycerol and peptone as suitable carbon and nitrogen sources, respectively. Comparative transcriptomic profiling was performed using RNA sequencing. It indicated that the differentially expressed genes (DEGs) of carbon were enriched using amino acids and carbohydrates via the transport and metabolism pathways, respectively. DEGs of nitrogen were enriched only using general functional prediction pathways. These data provide a comprehensive interpretation of the linkage between primary and secondary metabolisms in M. kaoliang. Moreover, they provide insights into the effects of various substances involved in secondary metabolism.

Comparative Transcriptomic and Metabolomic Analyses Reveal the Regulatory Effect and Mechanism of Tea Extracts on the Biosynthesis of Monascus Pigments.

Monascus pigments (MPs) are natural edible pigments with high safety and strong function, which have been widely used in food and health products. In this study, different types of tea extracts (rich in polyphenols) were used to regulate the biosynthesis of MPs. The results showed that 15% ethanol extract of pu-erh tea (T11) could significantly increase MPs production in liquid fermentation of Monaco's purpureus M3. Comparative transcriptomic and metabolomic analyses combined with reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to further explore the regulatory mechanism of T11 on the biosynthesis of MPs. Comparative transcriptomic analysis showed that there were 1503 differentially expressed genes (DEGs) between the Con group and the T11 group, which were mainly distributed in carbohydrate metabolism, amino acid metabolism, energy metabolism, lipid metabolism, metabolism of terpenoids and polyketides, etc. A total of 115 differential metabolites (DMs) identified by metabolomics between the Con and T11 groups were mainly enriched in glutathione metabolism, starch and sucrose metabolism, alanine, aspartic acid and glutamate metabolism and glycine, serine and threonine metabolism, etc. The results of metabolomics were basically consistent with those of gene transcriptomics, indicating that the regulatory effect of T11 on the biosynthesis of MPs is mainly achieved through affecting the primary metabolic pathway, providing sufficient energy and more biosynthetic precursors for secondary metabolism. In this study, tea extracts with low economic value and easy access were used as promoters of MPs biosynthesis, which may be conducive to the application of MPs in large-scale industrial production. At the same time, a more systematic understanding of the molecular regulatory mechanism of Monascus metabolism was obtained through multi-omics analysis.

Carbon Arc Lamp Therapy Enhances the Repair Potential of Chronic Soft Tissue Injury in Rats Compared with the Ability of Photobiomodulation Therapy.

Objective: The effects of photobiomodulation therapy (PBMT) and carbon arc lamp therapy (CALT) on the repair of chronic soft tissue injury were compared. Background data: PBMT improves soft tissue repair of chronic injury. However, there has been no research on the effect of CALT. Methods: Human umbilical vein endothelial cells (HUVECs) were irradiated using PBMT and CALT at 2 J/cm2 to observe their effects on cell proliferation and migration. The effects of PBMT and CALT on soft tissue injury repair were assessed using a chronic gastrocnemius injury model of the posterior limb in rats. The malondialdehyde (MDA), superoxide dismutase (SOD), and prostaglandin E2 (PGE2) were examined by biochemical analyses. The degree of tissue damage repair was evaluated by the immunohistochemical method [CD45, CD34, vascular endothelial growth factor (VEGF), and actin] and the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method. Results: Treatment by PBMT and CALT significantly accelerated the proliferation and migration of HUVECs. Moreover, significant decreases in the contents of MDA and PGE2 were observed in the PBMT and CALT groups, while SOD activity was increased. The histological assessment shows that the content of inflammatory cells and apoptotic cells significantly decreased in the CALT group. However, the microvascular density, VEGF content, and actin content were increased in the CALT group. Conclusions: The results demonstrate that CALT has a stronger effect on promoting chronic soft tissue injury repair in comparison with PBMT.

Decellularized adipose tissue: A key factor in promoting fat regeneration by recruiting and inducing mesenchymal stem cells.

BACKGROUND: Decellularized adipose tissue (DAT) has attracted much attention due to its wide range of sources and adipose regeneration capacity. However, the lipogenic efficiency of DAT is still controversial due to its unclear mechanism. To this point, it is crucial to clarify the mechanism of DAT in promoting adipose regeneration Objective: This study aims to explore the mechanism of DAT promoting adipose regeneration and survival mechanism of DAT transplantation in vivo. METHODS: DAT preparation by repeated freeze-thaw, enzymatic digestion, and isopropanol degreasing. Histology, DAPI, immunohistochemistry, immunofluorescence and scanning electron microscopy confirmed the efficacy and reproducibility of these approaches. BM-MSCs, ADSCs and UCMSCs were cocultured with DAT for 14 days and then stained with oil red O. Adipogenic genes of three MSCs were detected by RT-PCR. DAT and adipose tissue were transplanted subcutaneously into the back of nude mice to observe medium and long-term morphological changes, vascularization, and lipid-forming efficiency. Mass spectrometry (MS)-based proteomic to analyze the adipogenic protein contents of DAT and adipose tissue. RESULTS: The DAT without any cellular components but with an abundance of collagen; neither DNA nor lipids were detected. Seeding experiments with MSCs indicated that the DAT provided an inductive microenvironment for adipogenesis, supporting the expression of the master regulators PPARγ. Within four months after transplantation, HE morphology of DAT was identical to adipose cells. Immunofluorescence markers CD31 and perilipin were increased in DAT, while the retention rate gradually decreased over time, eventually accounting for 33.7% of the original volume. MS-based proteomic analyses identified 1013 types of proteins in adipose tissue and 29 proteins in the DAT. Analyses of GO and KEGG databases suggested that DAT contained a variety of proteins involved in fat metabolism. CONCLUSIONS: DAT can interact with different types of MSCs and ultimately achieve adipose regeneration. The presence of multiple adipogenic proteins in DAT make it play a vital role in adipose regeneration. DAT is expected to be an ideal bio-derived scaffold for adipose tissue engineering.

Ganoderic acid A from Ganoderma lucidum ameliorates lipid metabolism and alters gut microbiota composition in hyperlipidemic mice fed a high-fat diet.

Ganoderic acid A (GA) is one of the most abundant triterpenoids in Ganoderma lucidum, and has been proved to possess a wide range of beneficial health effects. The aim of the current study is to investigate the amelioration effects and mechanism of GA on improving hyperlipidemia in mice fed a high-fat diet (HFD). The results showed that GA intervention significantly inhibited the abnormal growth of body weight and epididymal white adipose tissue (eWAT), prevented the hypertrophy of epididymal adipocytes, and ameliorated the biochemical parameters of serum and liver related to lipid metabolism in HFD-fed mice. Histological analysis also showed that the excessive accumulation of lipid droplets in the liver induced by HFD-feeding was greatly alleviated by GA intervention. In addition, GA intervention also increased the level of short chain fatty acids (SCFAs) in the intestine and promoted the excretion of bile acids (BAs) through feces. High-throughput sequencing of bacterial full-length 16S rDNA revealed that daily supplementation with GA made significant structural changes in the gut microbial population of mice fed with HFD, in particular modulating the relative abundance of some function related microbial phylotypes. The relationships between lipid metabolic parameters and gut microbial phylotypes were also revealed by correlation analysis based on a heatmap and network. The result showed that 46 key gut microbial phylotypes (OTUs) were markedly correlated with at least one lipid metabolic parameter. Moreover, UPLC-QTOF/MS-based liver metabolomics showed that 111 biomarkers (47 up-regulated metabolites and 64 down-regulated metabolites) were significantly changed after high-dose GA intervention (75 mg kg-1 day-1), compared with the HFD-fed hyperlipidemic mice. Metabolic pathway enrichment analysis of the differential hepatic metabolites demonstrated that GA intervention had significant regulatory effects on primary bile acid biosynthesis, fatty acid biosynthesis, amino sugar and nucleotide sugar metabolism, inositol phosphate metabolism, and so on. In addition, GA intervention regulated the mRNA levels of hepatic genes involved in fatty acid metabolism and bile acid homeostasis. These findings present new evidence supporting that GA from G. lucidum has the potential to alleviate lipid metabolic disorders and ameliorate the imbalance of gut microflora in a positive way.

Comparative transcriptomic analysis reveals the regulatory effects of inorganic nitrogen on the biosynthesis of Monascus pigments and citrinin.

Monascus spp. and its secondary metabolites have been widely applied in foods and medicines for thousands of years in eastern Asia. Nitrogen sources are essential nutrients for the growth and metabolism of Monascus spp. Our previous study found that inorganic nitrogen sources (especially NH4Cl and NH4NO3) promoted the biosynthesis of Monascus pigments (MPs) and inhibited the production of citrinin. The objective of the present study was to investigate the regulatory mechanism of inorganic nitrogen on the biosynthesis of MPs and citrinin by the comparative transcriptional approach (RNA sequencing combined with RT-qPCR). Results indicated that the submerged fermentation of M. purpureus M3103 with NH4Cl or NH4NO3 as the sole nitrogen source can significantly increase the yields of MPs (especially for Monascus orange and red pigments) and decrease citrinin production, compared with the organic nitrogen source (peptone group). Comparative transcriptomic profiling by RNA sequencing found that the numbers of differentially expressed genes (DEGs) between different experimental groups-M group (peptone group) vs. ML group (NH4Cl group), and M group (peptone group) vs. MX group (NH4NO3 group), were 722 and 1287, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that genes involved in carbon and nitrogen metabolism, biosynthesis of amino acids were up-regulated by NH4Cl and NH4NO3, which would produce more biosynthetic precursors for MPs. Whereas, the inorganic nitrogen source (both of NH4Cl and NH4NO3) down-regulated the expression levels of genes involved in tyrosine metabolism. In addition, NR analysis indicated that the essential genes and transcription factors involved in the biosynthesis pathway of citrinin were down-regulated by NH4Cl and NH4NO3. These results indicated that NH4Cl or NH4NO3 as a nitrogen source for M. purpureus M3103 can significantly promote the precursor synthesis of Monascus pigments, but reduce the transcription of polyketide synthase for citrinin, and therefore significantly increase Monascus pigments production and decrease citrinin formation. These findings will facilitate a comprehensive understanding of the regulatory mechanisms of inorganic nitrogen in the biosynthesis of secondary metabolites in M. purpureus, and would benefit the application of M. purpureus in the production of MPs.

Facial intramuscular lipoma occurrence following topical cosmetic injection with a mixture of basic fibroblast growth factor: A report of two cases.

Growth factors and cytokines control cell growth, proliferation and differentiation via a network of inter- and intracellular signalling pathways, and are involved in skin self-renewing and wound healing. In recent years, topical and injectable growth factors and cytokines have emerged as an intriguing therapeutic modality that can be harnessed for aesthetic purposes. However, very little data are available on their long-term safety and tolerability. In this report, we describe two cases of patients, who developed intramuscular lipoma of the chin following topical injection with a mixture of basic fibroblast growth factor as the main ingredients for chin augmentation. Biopsies in the two cases were performed at our department, and revealed intramuscular lipoma. Our report indicates that the topical injection of growth factors can lead to tumorigenesis, so health care providers need to be aware of its potential consequences.

Effects of topical oxygen therapy on ischemic wound healing.

[Purpose] This study evaluated the effects of topical oxygen therapy on the hind limb wounds of rats under ischemic conditions. [Subjects and Methods] Twelve injured rats were treated with topical oxygen on skin wounds located on the hind limb and compared with twelve injured control rats. Indexes including gross morphology of the wound, wound healing time, wound healing rate, and histological and immunohistochemical staining of sections of wound tissue were examined at different time points after intervention. [Results] The wound healing time was shorter in the topical oxygen therapy group than the control group. The wound healing rate and granulation tissue formation in the topical oxygen therapy group showed significant improvement on days 3, 7, and 14. Through van Gieson staining, the accumulation of collagen fiber in the topical oxygen therapy group was found to have improved when compared with the control group on day 7. Through semiquantitative immunohistochemical staining, many more new vessels were found in the topical oxygen therapy group compared with the model control group on day 7. [Conclusion] The results of the experiment showed that topical oxygen therapy improved ischemic wound healing.

Combined alloplastic implant and autologous dermis graft for nasal augmentation rhinoplasty in Asians.

UNLABELLED: Alloplastic implants may be used in augmentation rhinoplasty but are associated with thinning of the skin over the implant as well as extrusion and translucency of the implant. To minimize these complications, this report describes a combined alloplastic implant and autologous dermal graft for dorsal and tip augmentation rhinoplasty. Of 37 Chinese patients, 35 (94.6 %) were satisfied with the outcome of this procedure during a follow-up period of up to 24 months, and no implant extrusions occurred. The preliminary findings indicate that a combined alloplastic implant and autologous dermis graft is appropriate for nasal augmentation, especially for patients with thin tip skin. LEVEL OF EVIDENCE V: 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 .

[The change of angiotensin II production and its receptor expression during wound healing: possible role of angiotensin II in wound healing].

OBJECTIVE: This study was undertaken to observe the change in the local level of angiotensin II (Ang II) and the expression of its corresponding receptors AT1 and AT2 during wound healing, and explore the possible role of Ang II in wound healing . METHODS: A model of full-thickness cutaneous wound was developed on the back of C57/BL6 mice. Specimens were taken from the wound of each mouse on the day 0, 1, 3, 5, 7, 9, 11, 13 and 15 after wounding. The change in the generation of Ang II in wounded tissue during the healing process was detected with ELISA. The proliferation and the apoptosis of cells were detected by bromodeoxyuridine (Brdu) and terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling (TUNEL) method in wounded skin during the healing process, respectively. The cellular localization and the mRNA level change of Ang II receptors in wounded tissue during healing were detected with immunostaining and RT-PCR. RESULTS: Ang II produced in wounded skin was increased in the first 7 days to reach the peak, and then gradually decreased during wound healing. BrdU labeling index was increased gradually in the first 7 days to reach the peak, and then gradually decreased during wound healing. The number of TUNEL-positive cells was increased slowly in the first 7 days after wounding. The increase in the number of TUNEL-positive cells was more markedly after epithelization of the wound. In normal mice, AT1 and AT2 receptor were found positively expressed in the whole epidermal layer, while positive expression was only found in the endothelial cells of the capillary vessels within the dermal layer, and positive expression was also found in appendages of the skin, i. e. hair follicle, sweat gland and sebaceous gland respectively. Positive staining signal of both AT1 and AT2 receptors were increased in the first 7 days to reach the peak, then gradually decreased. Expression of AT2R was increased again following the epithelization of wound. The result of RT-PCR showed that the expression of both AT1 and AT2 receptors was detectable, and AT1 receptor was increased in the first 7 days to the peak, and then gradually decreased during wound healing, while AT2 receptor expression reached its peak value on day 7, then gradually decreased, and increased again following the epithelization of wound. CONCLUSIONS: These results indicate that Ang II participate in wound repair and related to remolding in the late stage of wound healing through the change in production of angiotensin II and expression of AT1 and AT2 receptors. AT1 receptor might be closely associated with cell proliferation, while AT2 receptor might play a role in cell apoptosis and remolding during wound healing.