Translational research : the journal of laboratory and clinical medicine
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There is significant interest in understanding the cellular mechanisms responsible for expedited healing response in various oral tissues and how they are impacted by systemic diseases. Depending upon the types of oral tissue, wound healing may occur by predominantly re-eptihelialization, by re-epithelialization with substantial new connective tissue formation, or by a a combination of both plus new bone formation. As a result, the cells involved differ and are impacted by systemic diaseses in various ways. ⋯ In particular, diabetes inhibits the expression of mitogenic growth factors whereas that of pro-inflammatory cytokines is elevated through epigenetic mechanisms. Moreover, hyperglycemia and oxidative stress induced by diabetes prevents the expansion of mesengenic cells that are involved in both soft and hard tissue oral wounds. A better understanding of how diabetes influences the healing processes is crucial for the prevention and treatment of diabetes-associated oral complications.
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Review
Immune responses to injury and their links to eye disease: Immune responses to wounding in the eye.
The eye is regarded as an immune privileged site. Since the presence of a vasculature would impair vision, the vasculature of the eye is located outside of the central light path. As a result, many regions of the eye evolved mechanisms to deliver immune cells to sites of dysgenesis, injury, or in response to the many age-related pathologies. ⋯ The response to traumatic or pathological injury is distinct in different regions of the eye. Age-related diseases impact both the anterior and posterior segment and lead to reduced quality of life and blindness. Here we focus attention on the role that inflammation and fibrosis play in the progression of age-related pathologies of the cornea and the lens as well as in glaucoma, the formation of epiretinal membranes, and in proliferative vitreoretinopathy.
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Following injury, the oral mucosa undergoes complex sequences of biological healing processes to restore homeostasis. While general similarities exist, there are marked differences in the genomics and kinetics of wound healing between the oral cavity and cutaneous epithelium. The lack of successful therapy for oral mucosal wounds has influenced clinicians to explore alternative treatments and potential autotherapies to enhance intraoral healing. ⋯ Studies were evaluated by injury models, therapy interventions, and outcome measures. The success of therapeutic approaches was assessed, and research outcomes were compared based on current hallmarks of oral wound healing. By leveraging therapeutic advancements, particularly within in cell-based biomaterials and immunoregulation, there is great potential for translational therapy in oral tissue regeneration.
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Hypertrophic scars are the most common post-burn complications characterized by fibroblast proliferation and excessive extracellular matrix deposition. The intermediate-conductance Ca2+-activated K+ channel (KCa3.1) mediates fibroblast activation, resulting in several fibrotic diseases; however, this channel's role in the formation of post-burn hypertrophic skin scars remains unknown. Herein, we investigated the role of KCa3.1 and the therapeutic potential of TRAM-34, a selective inhibitor of KCa3.1, in hypertrophic skin scar formation following burn injury. ⋯ Anti-scarring molecular, histological, and visual effects of TRAM-34 were confirmed in murine burn models. Altered subcellular expression of KCa3.1 is a novel mechanism underlying the cellular response to burn injury. Our results suggest that selective inhibition of KCa3.1 by TRAM-34 has therapeutic potential against post-burn hypertrophic scar formation.
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The concept of gap junctions and their role in intercellular communication has been known for around 50 years. Considerable progress has been made in understanding the fundamental biology of connexins in mediating gap junction intercellular communication (GJIC) and their role in various cellular processes including pathological conditions. However, this understanding has not led to development of advanced therapeutics utilizing GJIC. ⋯ AsODN, antisense oligodeoxynucleotides; BMPs, bone morphogenetic proteins; BMSCs, bone marrow stem cells; BG, bioglass; Cx, Connexin; CxRE, connexin-responsive elements; CoCr NPs, cobalt-chromium nanoparticles; cGAMP, cyclic guanosine monophosphate-adenosine monophosphate; cAMP, cyclic adenosine monophosphate; ERK1/2, extracellular signal-regulated kinase 1/2; EMT, epithelial-mesenchymal transition; EPA, eicosapentaenoic acids; FGFR1, fibroblast growth factor receptor 1; FRAP, fluorescence recovery after photobleaching; 5-FU, 5-fluorouracil; GJ, gap junction; GJIC, gap junctional intercellular communication; HGPRTase, hypoxanthine phosphoribosyltransferase; HSV-TK, herpes virus thymidine kinase; HSA, human serum albumin; HA, hyaluronic acid; HDAC, histone deacetylase; IRI, ischemia reperfusion injury; IL-6, interleukin-6; IL-8, interleukin-8; IONPs, iron-oxide nanoparticles; JNK, c-Jun N-terminal kinase; LAMP, local activation of molecular fluorescent probe; MSCs, mesenchymal stem cells; MMP, matrix metalloproteinase; MI, myocardial infarction; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor kappa B; NO, nitric oxide; PKC, protein kinase C; QDs, quantum dots; ROI, region of interest; RGO, reduced graphene oxide; siRNA, small interfering RNA; TGF-β1, transforming growth factor-β1; TNF-α, tumor necrosis factor-α; UCN, upconversion nanoparticles; VEGF, vascular endothelial growth factor. In this review, we discuss briefly the role of connexins and gap junctions in various physiological and pathological processes, with special emphasis on cancer. We further discuss the application of nanotechnology and tissue engineering in developing treatments for various connexin based disorders.