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At least 19 recordsLinked to original sources
PubMed2024

Spatiotemporal single-cell roadmap of human skin wound healing.

Wound healing is vital for human health, yet the details of cellular dynamics and coordination in human wound repair remain largely unexplored. To address this, we conducted single-cell multi-omics analyses on human skin wound tissues through inflammation, proliferation, and remodeling phases of wound repair from the same individuals, monitoring the cellular and molecular dynamics of human skin wound healing at an unprecedented spatiotemporal resolution. This singular roadmap reveals the cellular architecture of the wound margin and identifies FOSL1 as a critical driver of re-epithelialization. It shows that pro-inflammatory macrophages and fibroblasts sequentially support keratinocyte migration like a relay race across different healing stages. Comparison with single-cell data from venous and diabetic foot ulcers uncovers a link between failed keratinocyte migration and impaired inflammatory response in chronic wounds. Additionally, comparing human and mouse acute wound transcriptomes underscores the indispensable value of this roadmap in bridging basic research with clinical innovations.

Humans↗
PubMed2026

Impact of NR4A3 on wound healing in chronic venous ulcers and its association with the PI3K/Akt signaling pathway.

BACKGROUND: To investigate the role of NR4A3 in chronic venous ulcer (VU) wound healing and to explore its potential regulatory mechanism involving the PI3K/Akt pathway. METHODS: Differential expression and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the GSE174661 dataset. DEGs were filtered by |log2FC| > 1 and adjusted P < 0.05, with KEGG significance set at P < 0.05. NR4A3 was identified as the core gene. NR4A3 knockdown and overexpression were established in HaCaT cells to evaluate proliferation, migration, and inflammatory cytokines. TNF-&#x3b1; was used to mimic the inflammatory microenvironment. Western blotting assessed phosphorylation of GSK3&#x3b2;, mTOR, PI3K, and Akt. PI3K/Akt agonist 740Y-P and inhibitor LY294002 were used in rescue experiments. RESULTS: Bioinformatic analysis revealed that NR4A3 expression was markedly downregulated in chronic venous ulcer (VU) tissues relative to normal skin and ordinary acute wound tissues. Differentially expressed genes were significantly enriched in the PI3K/Akt signaling pathway. TNF-&#x3b1; stimulation significantly upregulated NR4A3 expression and increased phosphorylation of GSK3&#x3b2; and mTOR in HaCaT cells. In cultured HaCaT keratinocytes, NR4A3 knockdown suppressed cell proliferation and invasion, enhanced cell migration, and elevated the expression and secretion of pro-inflammatory cytokines (IL-6, IL-8, CXCL5), accompanied by reduced phosphorylation of PI3K and Akt. Conversely, NR4A3 overexpression promoted cell proliferation and invasion, restrained migration, and dampened inflammatory responses, while increasing PI3K/Akt phosphorylation. Treatment with the PI3K/Akt agonist 740Y-P partially rescued the impaired proliferation, aberrant migration, and excessive inflammation caused by NR4A3 silencing, whereas PI3K/Akt inhibitor LY294002 aggravated pathway suppression. These findings suggest that NR4A3-associated changes in keratinocyte functions and inflammatory reactions are functionally linked to PI3K/Akt pathway activity, and inflammatory stimulation activates GSK3&#x3b2;/mTOR signaling accompanied by compensatory NR4A3 upregulation. CONCLUSION: These findings suggest that NR4A3 is associated with keratinocyte behavior and inflammatory responses via the PI3K/Akt pathway, potentially affecting chronic VU progression and healing. Reduced NR4A3 may impair wound repair through inflammation and abnormal cell migration, while TNF-&#x3b1; induces compensatory NR4A3 elevation.

NR4A3↗
PubMed1977

Increased blood-brain barrier permeability around cerebral stab wounds, aggravated by acute ethanol intoxication.

Control and ethanol-intoxicated rats were injured with a small cerebral stab wound and the extravasation of Evans blue-labelled albumin (EBA) was studied. Control rats displayed an extravasation of EBA in the immediate peri-traumatic area with subsequent uptake of EBA in neurons and glia. Ethanol-intoxicated rats showed a greater leakage of EBA as well as a wider area of leaking blood vessels around the stab wound, both in the peri-traumatic and in the early post-traumatic period. Neuronal uptake of EBA was enhanced and observed in a wider area in intoxicated than control rats. The difference in distribution of EBA among neurons and glia between intoxicated and control rats was partly a consequence of the difference in leakage of EBA in the experimental groups. However, part of the increased neuronal uptake of EBA might be explained by an effect of ethanol on nueronal plasmalemma. The results obtained indicated a more pronounced injury to endothelial and neuronal cells after small cerebral stab wounds in ethanol-intoxicated compared to control rats.

Alcoholic Intoxication↗
PubMed1978

Ultrastructural studies on blood-brain barrier dysfunction around cerebral stab wounds, aggravated by acute ethanol intoxication.

Ethanol-intoxicated and non-intoxicated albino rats subjected to cerebral stab wounds were injected with Evans blue-labelled albumin (EBA) and horseradish peroxidase (HRP) 24 hours after the injury. The tracers were injected 30 and 2 minutes before perfusion fixation with glutaraldehyde and then prepared for light microscopy and electron microscopy. There was prominent leakage of peroxidase through chains of pinocytotic vesicles and transendothelial channels from blood, through the endothelial cells, into the brain. There was no difference in the way of peroxidase leakage through the endothelial cells between ethanol-intoxicated and control rats, but the area containing leaking blood vessels was greater in intoxicated rats. Furthermore, the number of trans-endothelial channels, vesicles and caveolae per unit length of capillaries and venules was increased in ethanol-intoxicated rats. Injured neurons with a diffuse distribution of peroxidase in their cytoplasm were observed within a greater area around the stab wound in ethanol-intoxicated than in control rats.

Alcoholic Intoxication↗
PubMed1979

Biologic determinants of tumor growth in healing wounds.

The morphologic characteristics of a scar may render it an "immunologically privileged site" providing fertile ground for tumor occurrence and growth. We sought to extend this concept and to determine the effect of different stages of wound healing on tumor occurrence. Syngeneic strain-2 guinea pigs and a methylcholanthrene-induced liposarcoma (MCA-2) were used. Incisional flank wounds were created at appropriate intervals such that at the time of tumor inoculation each group of animals had a sequentially aged wound which was a) acute, b) three weeks old, c) nine weeks old, d) 11 weeks old, e) created one week after tumor injection, or f) no wound. Wounds which were three, nine, or 11 weeks old consistently caused a significant increase in tumor growth rate following inoculation of a single cell tumor suspension (<.001). The delayed wounds, or those created following after tumor injection, and the acute wounds did not promote increased tumor growth. This study demonstrates that the ability of a wound to amplify or retard tumor growth may vary with its age. As a postulate we suggest that the relative paucity of lymphatic regeneration within scar tissue may render it an "immunologically privileged site" such that early recognition and destruction of tumor cells within the scar may be delayed long enough for the tumor to grow to a "critical size." Subsequent to this regardless of the host's immunocompetence the tumor can no longer be destroyed by an immune mechanism. The general lack of progressive growth of tumor cells placed in acute wounds suggests that they were not protected from immunocompetent cells and were destroyed by the ongoing inflammatory response to injury. Therefore, different biologic characteristics of a surgical scar are important in potentiating or retarding tumor growth. Variations in such factors may account for the local recurrence of cancer in operative wounds.

Animals↗
PubMed1978

[Diagnosis and therapy of acute penetrating myocardial injury (author's transl)].

Clinical signs of an acute penetrating wound of the heart not always are clear. Because of hemorrhage and reduced cardiac output during heart tamponade venous pressure not necessarily must be increased. If by pericardiocentesis an aspiration of blood is possible, diagnosis of a penetrating heart wound is of high probability; otherwise there is no diagnostic value of a negative pericardiocentesis. Only in a case of a very small cardiac wound pericardial drainage can be used as a sole therapeutic proceeding; clinical observation is mandatory and an emergency operation at all time must be possible. In most cases immediately thoracotomy with suture of the cardiac wound should be performed. Attention is necessary because of an injury of a coronary artery. Following this principle prognosis is good if the patient is reaching clinical treatment alive. Lethal outcome in 2 of our 12 reported cases in one of them is caused by refusing immediate surgical intervention by the patient himself, in the other by development of ischemic cardiac necrosis involving a papillary muscle after suturing a cardiac wound.

Acute Disease↗
PubMed1979

Acute effect of open joint wounds on articular cartilage and synovium in rabbits.

Open joint wounds were made in immature and mature rabbit knees by surgical arthrotomy. The wounds of the right knees were packed open for 5 days and the left knee wounds were closed primarily. The biochemical studies were selected to determine the effect of our treatment regimen on changes in the metabolism of articular cartilage and synovium. Neither closed nor open treatment produced significant changes in enzyme activities measured in the articular cartilage as compared to the controls in either immature or mature rabbits. Most of the synovial enzymes were elevated in the injured joints. There were, however, no significant differences in enzyme activity between the joints treated by either open or closed methods. Our findings suggest that short-term open treatment wounds does not cause matrix degradation in the cartilage nor affect the synovium more than simple arthrotomy.

Acetylgalactosamine↗
PubMed1979

Influence of Alvogyl on the healing of extraction wound in man.

Eight volunteer patients free of any systamic disease underwent extraction of two teeth on the same day. One extraction socket was packed with Alvogyl, the other served as a control wound. Biopsies for histological assessment were taken from both sockets 1 and 2 weeks after extraction. Histological study revealed the normal sequence of wound healing in the sockets allowed to heal spontaneously. On the other hand, the signs of retarded wound healing (acute inflammatory infiltrate, persistent granulation tissue, failure to form connective tissue scar and frequent foreign bodies/foreign body giant cells) were encountered in the sockets packed with Alvogyl. On the basis of these preliminary results, it seems warranted to state that the systematic use of Alvogyl as a preventive and curative treatment for postextraction alveolar infections cannot be advocated.

Adult↗
PubMed2024

Accelerating diabetic wound healing by ROS-scavenging lipid nanoparticle-mRNA formulation.

Current treatment options for diabetic wounds face challenges due to low efficacy, as well as potential side effects and the necessity for repetitive treatments. To address these issues, we report a formulation utilizing trisulfide-derived lipid nanoparticle (TS LNP)-mRNA therapy to accelerate diabetic wound healing by repairing and reprogramming the microenvironment of the wounds. A library of reactive oxygen species (ROS)-responsive TS LNPs was designed and developed to encapsulate interleukin-4 (IL4) mRNA. TS2-IL4 LNP-mRNA effectively scavenges excess ROS at the wound site and induces the expression of IL4 in macrophages, promoting the polarization from the proinflammatory M1 to the anti-inflammatory M2 phenotype at the wound site. In a diabetic wound model of db/db mice, treatment with this formulation significantly accelerates wound healing by enhancing the formation of an intact epidermis, angiogenesis, and myofibroblasts. Overall, this TS LNP-mRNA platform not only provides a safe, effective, and convenient therapeutic strategy for diabetic wound healing but also holds great potential for clinical translation in both acute and chronic wound care.

Wound Healing↗
PubMed1978

Age-related susceptibility to Pseudomonas aeruginosa ocular infections in mice.

The susceptibility of newborn and infant mice to eye infection by Pseudomonas aeruginosa was studied in 5-, 10-, 15- to 16-, and 21-day-old mice. In the first of three age-related susceptibility experiments, inoculation of P. aeruginosa under the unopened eyelids of infant (5- and 10-day-old) mice in the absence of prior corneal wounding resulted in acute infection and rapid death of many of the animals. However, endophthalmitis was observed in about 30% of bacteremic animals that survived to age 14 to 15 days. In the second experiment, 15- to 16-day-old mice whose eyes were open received P. aeruginosa topically onto either wounded or unwounded corneas. At least 50% of the mice that received both corneal wounding and the bacteria exhibited keratitis, endophthalmitis, and subsequent phthisis bulbi. None of the infected mice died of bacteremia. In addition, mice infected in the absence of corneal wounding did not exhibit any eye damage. In the third experiment, the wounded-cornea responses of 21-day-old mice to P. aeruginosa were more variable. Thirty seven percent of the mice exhibited an intermediate response of decreased eye size and cataracts which was not observed in 15- to 16-day-old mice, 32% recovered spontaneously, and 29% exhibited complete shrinkage of the infected eyes. The variability of the latter responses may reflect a transitional maturation period of natural immunity to the organism in some of the animals, since all 4- to 6-week-old adult mice respond routinely to ocular wounding and similar infections with the organism by undergoing a spontaneous resolvable keratitis (3 to 4 weeks).

Aging↗
PubMed1979

Value of cultures in patients with acute cellulitis.

A retrospective review of blood and wound cultures obtained from adult patients admitted for acute cellulitis revealed positive culture rates of 0.77% of 86% respectively. Organisms from wound cultures were predominantly Staphylococcus aureus and Streptococcus pyogenes. The majority of our patients were otherwise healthy. Our study suggests that blood cultures are not necessary in acute cellulitis in adults without serious underlying diseases.

Adolescent↗
PubMed1979

The effect of uraemia upon wound healing: an experimental study.

Acute uraemia was induced in rats by performing a 70 per cent nephrectomy. Uraemia was shown to delay the healing of intestinal anastomoses and abdominal wounds in rats as judged by bursting strength tests. Cellular proliferation was depressed at wound edges but there was no reduction in the total amount of hydroxyproline present in the wounds. Fibroblast growth in tissue culture was affected by the addition both of uraemic plasma and of urea solution to the culture medium. The possible causes of these effects are discussed.

Abdominal Muscles↗
PubMed1978

Surgical treatment of osteomyelitis in the metacarpal and metatarsal bones of the horse.

The case histories of four horses with osteomyelitis involving the metacarpal and metatarsal bones are reviewed and the surgical treatments discussed. The horses recovered after curettage of all infected tissue and post operative drainage. The role of antibiotics in treatment is considered and reference is made to the acute treatment of deep wounds to avoid osteomyelitis.

Animals↗