Wound healing represents a complex and evolutionarily conserved process across vertebrates, encompassing a series of life-rescuing events. The healing process runs in three main phases: inflammation, proliferation, and maturation/remodelling. While acute inflammation is indispensable for cleansing the wound, removing infection, and eliminating dead tissue characterised by the prevalence of neutrophils, the proliferation phase is characterised by transition into the inflammatory cell profile, shifting towards the prevalence of macrophages. The proliferation phase involves development of granulation tissue, comprising fibroblasts, activated myofibroblasts, and inflammatory and endothelial cells. Communication among these cellular components occurs through intercellular contacts, extracellular matrix secretion, as well as paracrine production of bioactive factors and proteolytic enzymes. The proliferation phase of healing is intricately regulated by inflammation, particularly interleukin-6. Prolonged inflammation results in dysregulations during the granulation tissue formation and may lead to the development of chronic wounds or hypertrophic/keloid scars. Notably, pathological processes such as autoimmune chronic inflammation, organ fibrosis, the tumour microenvironment, and impaired repair following viral infections notably share morphological and functional similarities with granulation tissue. Consequently, wound healing emerges as a prototype for understanding these diverse pathological processes. The prospect of gaining a comprehensive understanding of wound healing holds the potential to furnish fundamental insights into modulation of the intricate dialogue between cancer cells and non-cancer cells within the cancer ecosystem. This knowledge may pave the way for innovative approaches to cancer diagnostics, disease monitoring, and anticancer therapy.

• Keywords
• IL-6, cancer-associated fibroblasts, granulation tissue, myofibroblasts, wound healing,
• MeSH
• Autoimmunity * MeSH
• Wound Healing * immunology   MeSH
• Interleukin-6 * metabolism   immunology   MeSH
• Humans MeSH
• Tumor Microenvironment * immunology   MeSH
• Neoplasms * immunology   metabolism   pathology   MeSH
• Aging * immunology   MeSH
• Inflammation * immunology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Interleukin-6 * MeSH

OBJECTIVES: To compare palatal growth changes in infants with complete unilateral (UCLP) or bilateral (BCLP) cleft lip and palate during the first year of life. MATERIALS AND METHODS: Upper dental arches of 68 neonates with UCLP and BCLP were evaluated using 2D and 3D morphometry based on dental casts obtained in two age categories (T0 before early neonatal cheiloplasty-UCLP 4 ± 3 days, BCLP 6 ± 5 days; T1 before palatoplasty-UCLP 10 ± 2 months, BCLP 12 ± 3 months). RESULTS: Intensive palatal growth was manifested in both directions of the palate. Palatal growth in the anterior direction was not restricted, despite the intercanine (CC´) and anterior (LL´) widths being significantly narrowed in the BCLP group (CC´ p = 0.019, LL´ p = 0.009). The posterior dental arches were significantly enlarged (UCLP p ≤ 0.001; BCLP p ≤ 0.001). The negative effect of cleft severity on palatal length was not confirmed (p = 0.802). Variability of the palate was immense mainly in BCLP infants (T0); however, it decreased in both cleft types, confirming the formative effect of palatal growth leading to alveolar cleft closure (UCLP p ≤ 0.001; BCLP p = 0.006 on the right, 0.005 on the left). CONCLUSIONS: Both analyzed cleft groups (UCLP, BCLP) grew favorably during the first year of life, and the palatal growth was not limited in any direction. CLINICAL RELEVANCE: Geometric morphometry allowed a comprehensive analysis of the palate, which can contribute to the improvement of surgical methods.

• Keywords
• Bilateral cleft lip and palate, Classic morphometry, Early neonatal cheiloplasty, Geometric morphometry, Unilateral cleft lip and palate, Upper dental arches,
• MeSH
• Infant MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Cleft Palate * surgery   MeSH
• Cleft Lip * surgery   MeSH
• Plastic Surgery Procedures * MeSH
• Dental Arch surgery   MeSH
• Check Tag
• Infant MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Publication type
• Journal Article MeSH

This study tested whether cell cycle inhibitor mitomycin C (MMC) prevents arthrogenic contracture progression during remobilization by inhibiting fibroblast proliferation and fibrosis in the joint capsule. Rat knees were immobilized in a flexed position to generate flexion contracture. After three weeks, the fixation device was removed and rat knees were allowed to freely move for one week. Immediately after and three days after fixator removal, rats received intra-articular injections of MMC or saline. The passive extension range of motion (ROM) was measured before and after myotomy of the knee flexors to distinguish myogenic and arthrogenic contractures. In addition, both cellularity and fibrosis in the posterior joint capsule were assessed histologically. Joint immobilization significantly decreased ROMs both before and after myotomy compared with untreated controls. In saline-injected knees, remobilization increased ROM before myotomy, but further decreased that after myotomy compared with that of knees immediately after three weeks of immobilization. Histological analysis revealed that hypercellularity, mainly due to fibroblast proliferation, and fibrosis characterized by increases in collagen density and joint capsule thickness occurred after remobilization in saline-injected knees. Conversely, MMC injections were able to prevent the remobilization-enhanced reduction of ROM after myotomy by inhibiting both hypercellularity and joint capsule fibrosis. Our results suggest that joint capsule fibrosis accompanied by fibroblast proliferation is a potential cause of arthrogenic contracture progression during remobilization, and that inhibiting fibroblast proliferation may constitute an effective remedy.

• MeSH
• Fibroblasts drug effects   MeSH
• Immobilization adverse effects   MeSH
• Injections, Intra-Articular MeSH
• Joint Capsule drug effects   MeSH
• Contracture drug therapy   etiology   MeSH
• Mitomycin administration & dosage   MeSH
• Rats, Wistar MeSH
• Drug Evaluation, Preclinical MeSH
• Cell Proliferation drug effects   MeSH
• Antibiotics, Antineoplastic administration & dosage   MeSH
• Range of Motion, Articular drug effects   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Mitomycin MeSH
• Antibiotics, Antineoplastic MeSH

Melanoma represents a malignant disease with steadily increasing incidence. UV-irradiation is a recognized key factor in melanoma initiation. Therefore, the efficient prevention of UV tissue damage bears a critical potential for melanoma prevention. In this study, we tested the effect of UV irradiation of normal keratinocytes and their consequent interaction with normal and cancer-associated fibroblasts isolated from melanoma, respectively. Using this model of UV influenced microenvironment, we measured melanoma cell migration in 3-D collagen gels. These interactions were studied using DNA microarray technology, immunofluorescence staining, single cell electrophoresis assay, viability (dead/life) cell detection methods, and migration analysis. We observed that three 10 mJ/cm2 fractions at equal intervals over 72 h applied on keratinocytes lead to a 50% increase (p < 0.05) in in vitro invasion of melanoma cells. The introduction cancer-associated fibroblasts to such model further significantly stimulated melanoma cells in vitro invasiveness to a higher extent than normal fibroblasts. A panel of candidate gene products responsible for facilitation of melanoma cells invasion was defined with emphasis on IL-6, IL-8, and CXCL-1. In conclusion, this study demonstrates a synergistic effect between cancer microenvironment and UV irradiation in melanoma invasiveness under in vitro condition.

• Keywords
• Cancer microenvironment, Cancer-associated fibroblasts, Chemokine, Cytokine, Keratinocytes, Melanoma,
• MeSH
• Fibroblasts cytology   pathology   MeSH
• Immunohistochemistry MeSH
• Neoplasm Invasiveness * MeSH
• Keratinocytes pathology   radiation effects   MeSH
• Coculture Techniques MeSH
• Cells, Cultured MeSH
• Humans MeSH
• Melanoma pathology   MeSH
• Ultraviolet Rays * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

The nonsyndromic cleft is one of the most frequent congenital defects in humans. Clinical data demonstrated improved and almost scarless neonatal healing of reparative surgery. Based on our previous results on crosstalk between neonatal fibroblasts and adult keratinocytes, the present study focused on characterization of fibroblasts prepared from cleft lip tissue samples of neonates and older children, and compared them with samples isolated from normal adult skin (face and breast) and scars. Although subtle variances in expression profiles of children and neonates were observed, the two groups differed significantly from adult cells. Compared with adult cells, differences were observed in nestin and smooth muscle actin (SMA) expression at the protein and transcript level. Furthermore, fibroblast to myofibroblast differentiation drives effective wound healing and is largely regulated by the cytokine, transforming growth factor-β1 (TGF-β1). Dysregulation of the TGF-β signalling pathway, including low expression of the TGF-β receptor II, may contribute to reducing scarring in neonates. Fibroblasts of facial origin also exhibited age independent differences from the cells prepared from the breast, reflecting the origin of the facial cells from neural crest-based ectomesenchyme.

• MeSH
• Actins genetics   metabolism   MeSH
• Biomarkers MeSH
• Models, Biological MeSH
• Cell Differentiation MeSH
• Cytokines genetics   metabolism   pharmacology   MeSH
• Child MeSH
• Adult MeSH
• Fibroblasts cytology   drug effects   metabolism   MeSH
• Immunohistochemistry MeSH
• Infant MeSH
• Skin cytology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Nestin genetics   metabolism   MeSH
• Infant, Newborn MeSH
• Child, Preschool MeSH
• Cell Proliferation drug effects   MeSH
• Cleft Lip pathology   surgery   MeSH
• Aged MeSH
• Signal Transduction MeSH
• Gene Expression Profiling MeSH
• Transforming Growth Factor beta genetics   metabolism   MeSH
• Plastic Surgery Procedures MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Infant MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Infant, Newborn MeSH
• Child, Preschool MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Actins MeSH
• Biomarkers MeSH
• Cytokines MeSH
• Nestin MeSH
• Transforming Growth Factor beta MeSH

Clinical evidence suggests that healing is faster and almost scarless at an early neonatal age in comparison with that in adults. In this study, the phenotypes of neonatal and adult dermal fibroblasts and keratinocytes (nestin, smooth muscle actin, keratin types 8, 14 and 19, and fibronectin) were compared. Furthermore, functional assays (proliferation, migration, scratch wound closure) including mutual epithelial‑mesenchymal interactions were also performed to complete the series of experiments. Positivity for nestin and α smooth muscle actin was higher in neonatal fibroblasts (NFs) when compared with their adult counterparts (adult fibroblasts; AFs). Although the proliferation of NFs and AFs was similar, they significantly differed in their migration potential. The keratinocyte experiments revealed small, poorly differentiated cells (positive for keratins 8, 14 and 19) in primary cultures isolated from neonatal tissues. Moreover, the neonatal keratinocytes exhibited significantly faster rates of healing the experimentally induced in vitro defects in comparison with adult cells. Notably, the epithelial/mesenchymal interaction studies showed that NFs in co-culture with adult keratinocytes significantly stimulated the adult epithelial cells to acquire the phenotype of small, non-confluent cells expressing markers of poor differentiation. These results indicate the important differences between neonatal and adult cells that may be associated with improved wound healing during the early neonatal period.

• MeSH
• Actins metabolism   MeSH
• Cell Differentiation MeSH
• Neural Crest cytology   MeSH
• Tissue Donors * MeSH
• Adult MeSH
• Epithelial Cells cytology   metabolism   MeSH
• Phenotype MeSH
• Fibroblasts cytology   metabolism   MeSH
• Fibronectins biosynthesis   MeSH
• Immunohistochemistry MeSH
• Keratinocytes cytology   metabolism   MeSH
• Stem Cells metabolism   MeSH
• Coculture Techniques MeSH
• Humans MeSH
• Mesoderm cytology   MeSH
• Myofibroblasts cytology   MeSH
• Nestin metabolism   MeSH
• Neuronal Plasticity MeSH
• Infant, Newborn MeSH
• Cell Movement MeSH
• Cell Proliferation MeSH
• Gene Expression Profiling MeSH
• Aging physiology   MeSH
• Gene Expression Regulation, Developmental MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• ACTA2 protein, human MeSH Browser
• Actins MeSH
• Fibronectins MeSH
• Nestin MeSH