Influence of Infection on Partially Ischemic Excisional Skin Wounds.

Background: Skin wounds, whether medically or incidentally induced, are always at a risk of becoming infected, but the infection risks are greater when the wounds are recovering under ischemic, poorly perfused conditions. which frequently infects cutaneous and soft tissue, can infect to a greater extent when wounds are poorly perfused. Bad as this may be, both MSSA and MRSA strains of can cause severe infections, with MRSA being considered more aggressive.

Cosmetic implant placement in the female breast yields an altered local and systemic immune response: evidence for breast cancer immunosurveillance.

Background: Women with cosmetic implants have lower rates of future breast cancer than the general population. We hypothesized the implant foreign body response could induce a local protective anti-cancer immunosurveillance. We expanded on our previous finding which showed women with breast implants have elevated antibody responses to certain breast cancer proteins.

Skin fibrosis is accompanied by increased expression of secreted frizzled-related protein-2.

Dermal fibrosis is a consequence of damage to skin and is accompanied by dysfunction and cosmetic disfigurement. Improved understanding of the pathological factors driving skin fibrosis is critical to development of therapeutic modalities. Here, we describe that the Wnt signalling antagonist SFRP2 is upregulated in organotypic keratinocyte cultures upon experimental reduced hydration, a model that simulates the aberrant epidermal barrier state characteristic of several skin pathologies, including those that manifest in development of fibrosis.

Differential Anti-Fibrotic and Remodeling Responses of Human Dermal Fibroblasts to sp., Artemisinin, and Its Derivatives.

Fibrosis is a ubiquitous pathology, and prior studies have indicated that various artemisinin (ART) derivatives (including artesunate (AS), artemether (AM), and dihydroartemisinin (DHA)) can reduce fibrosis in vitro and in vivo. The medicinal plant L. is the natural source of ART and is widely used, especially in underdeveloped countries, to treat a variety of diseases including malaria.

Anti-fibrotic effects of statin drugs: A review of evidence and mechanisms.

Fibrosis is a pathological repair process common among organs, that responds to tissue damage by replacement with non-functional connective tissue. Despite the widespread prevalence of tissue fibrosis, manifesting in numerous disease states across myriad organs, therapeutic modalities to prevent or alleviate fibrosis are severely lacking in quantity and efficacy. Alongside development of new drugs, repurposing of existing drugs may be a complementary strategy to elect anti-fibrotic compounds for pharmacologic treatment of tissue fibrosis.

Comment on "Scar-Degrading Endothelial Cells as a Treatment for Advanced Liver Fibrosis".

Cellular therapies show promise for treatment of fibrosis. A recent article presents a strategy and proof-of-concept for delivering stimulated cells to degrade hepatic collagen in vivo. A discussion is presented surrounding the strengths of this approach and the potential to generalize this strategy of optimizing cell sources and activation stimuli to treat other types of fibrosis.

Prediction and Demonstration of Retinoic Acid Receptor Agonist Ch55 as an Antifibrotic Agent in the Dermis.

The prevalence of fibrotic diseases and the lack of pharmacologic modalities to effectively treat them impart particular importance to the discovery of novel antifibrotic therapies. The repurposing of drugs with existing mechanisms of action and/or clinical data is a promising approach for the treatment of fibrotic diseases. One paradigm that pervades all fibrotic diseases is the pathological myofibroblast, a collagen-secreting, contractile mesenchymal cell that is responsible for the deposition of fibrotic tissue.

Epidermal Potentiation of Dermal Fibrosis: Lessons from Occlusion and Mucosal Healing.

Fibrotic skin conditions, such as hypertrophic and keloid scars, frequently result from injury to the skin and as sequelae to surgical procedures. The development of skin fibrosis may lead to patient discomfort, limitation in range of motion, and cosmetic disfigurement. Despite the frequency of skin fibrosis, treatments that seek to address the root causes of fibrosis are lacking.

Amnion membranes support wound granulation in a delayed murine excisional wound model.

Chronic or delayed healing wounds constitute an ever-increasing burden on healthcare providers and patients alike. Thus, therapeutic modalities that are tailored to particular deficiencies in the delayed wound healing response are of critical importance to improve clinical outcomes. Human amnion-derived viable and devitalized allografts have demonstrated clinical efficacy in promoting the closure of delayed healing wounds, but the mechanisms responsible for this efficacy and the specific wound healing processes modulated by these tissues are not fully understood.

Comparative transcriptomic adaptations of Staphylococcus aureus to the wound environment in non-diabetic and diabetic mice.

Infection is a major source of complications in delayed diabetic wound healing. Increased understanding of differential bacterial responses to diabetic wounds will enable us to better understand chronic wound pathogenesis. Here we create delayed-healing wounds infected with Staphylococcus aureus in non-diabetic and diabetic mice and used RNA-seq to compare bacterial gene expression profiles 3 or 7 days after infection.

Reduced hydration regulates pro-inflammatory cytokines via CD14 in barrier function-impaired skin.

Damage to epidermis results in loss of barrier function and resultant pathological inflammatory signaling, triggering further damage to the skin. Here we investigate transcriptomic datasets generated from varied skin pathologies associated with disrupted epidermis and pinpoint CD14/S100 signaling as a conserved pathway upregulated in dermatopathologies characterized by a compromised epidermal barrier. We show that dermatitic and fibrotic tissues of humans and mouse models, which are associated with compromised epidermal barrier, demonstrate upregulation of CD14 and S100 proteins, damage-associated molecular patterns (DAMPs), in the epidermis.

Simvastatin cream alleviates dermal fibrosis in a rabbit ear hypertrophic scar model.

Background: Hypertrophic scars (HTS) result from injury to the skin and represent a clinical burden with limited treatment options. Previously, we demonstrated that statin drugs could attenuate HTS formation, but convenient topical delivery and retention of these drugs at the wound site remains a challenge.

Aims: Here, we aimed to develop a topical cream formulation that can deliver statin drugs simply and conveniently to reduce scar hypertrophy.

Anti-fibrotic effects of pharmacologic FGF-2: a review of recent literature.

Fibrosis is a process of pathological tissue repair that replaces damaged, formerly functional tissue with a non-functional, collagen-rich scar. Complications of fibrotic pathologies, which can arise in numerous organs and from numerous conditions, result in nearly half of deaths in the developed world. Despite this, therapies that target fibrosis at its mechanistic roots are still notably lacking.

Comparison of Thermal Burn-Induced and Excisional-Induced Scarring in Animal Models: A Review of the Literature.

Scar formation is a natural result of mammalian wound healing. In humans and other mammals, however, deep dermal wounds and thermal injuries often result in formation of hypertrophic scars, leading to substantial morbidity and lending great importance to development of therapeutic modalities for burn scars. Thus, preclinical burn wound models that adequately simulate processes underlying human burn-induced wound healing, particularly those processes leading to chronic inflammation and development of hypertrophic scars, are critical to developing further treatment paradigms for clinical use.

Can Breast Implants Induce Breast Cancer Immunosurveillance? An Analysis of Antibody Response to Breast Cancer Antigen following Implant Placement.

Background: Women with cosmetic breast implants have significantly lower rates of subsequent breast cancer than the general population (relative risk, 0.63; 95 percent CI, 0.56 to 0.

The Na (SCN7A) channel: an atypical regulator of tissue homeostasis and disease.

Within an articulately characterized family of ion channels, the voltage-gated sodium channels, exists a black sheep, SCN7A (Na). Na, in contrast to members of its molecular family, has lost its voltage-gated character and instead rapidly evolved a new function as a concentration-dependent sensor of extracellular sodium ions and subsequent signal transducer. As it deviates fundamentally in function from the rest of its family, and since the bulk of the impressive body of literature elucidating the pathology and biochemistry of voltage-gated sodium channels has been performed in nervous tissue, reports of Na expression and function have been sparse.

Artemisinin and artemisinin derivatives as anti-fibrotic therapeutics.

Fibrosis is a pathological reparative process that can occur in most organs and is responsible for nearly half of deaths in the developed world. Despite considerable research, few therapies have proven effective and been approved clinically for treatment of fibrosis. Artemisinin compounds are best known as antimalarial therapeutics, but they also demonstrate antiparasitic, antibacterial, anticancer, and anti-fibrotic effects.

A dehydrated, aseptically-processed human amnion/chorion allograft accelerates healing in a delayed murine excisional wound model.

Since chronic, non-healing wounds represent an increasing source of economic and temporal burden for patients who suffer from them and healthcare professionals that treat them, therapeutic modalities that promote closure of delayed and non-healing wounds are of utmost importance. Recent clinical results of allografts derived from amnion and chorion placental layers encourage further investigation of the mechanisms underlying clinical efficacy of these products for treatment of wounds. Here, we utilized a diabetic murine splinted excisional wound model to investigate the effects of a dehydrated human amnion/chorion-derived allograft (dHACA) on delayed wound healing, as well as the effects of dehydrated allograft derived solely from amnion tissue of the same donor.

Application of decellularized human reticular allograft dermal matrix promotes rapid re-epithelialization in a diabetic murine excisional wound model.

Background Aims: The treatment and care of human wounds represent an enormous burden on the medical system and patients alike. Chronic or delayed healing wounds are characterized by the inability to form proper granulation tissue, followed by deficiencies in keratinocyte migration and wound re-epithelialization, leading to increased likelihood of infection and poor wound outcomes. Human reticular acellular dermal matrix (HR-ADM) is one type of tissue graft developed to enhance closure of delayed healing wounds that has demonstrated clinical utility through accelerating closure of lower extremity diabetic ulcers, but the mechanisms underlying this clinical success are not well understood.

Knockout of sodium channel Na delays re-epithelializathion of splinted murine excisional wounds.

Mammalian wound healing is a carefully orchestrated process in which many cellular and molecular effectors respond in concert to perturbed tissue homeostasis in order to close the wound and re-establish the skin barrier. The roles of many of these molecular effectors, however, are not entirely understood. Our lab previously demonstrated that the atypical sodium channel Na (encoded by Scn7a) responds to wound-induced epidermal dehydration, resulting in molecular cascades that drive pro-inflammatory signaling.

Allogeneic Decellularized Muscle Scaffold Is Less Fibrogenic and Inflammatory than Acellular Dermal Matrices in a Rat Model of Skeletal Muscle Regeneration.

Background: Skeletal muscle trauma can produce grave functional deficits, but therapeutic options remain limited. The authors studied whether a decellularized skeletal muscle scaffold would provide benefits in inducing skeletal muscle regeneration over acellular dermal matrices.

Methods: Eighty-two rat muscle defects were surgically created and assigned to no intervention or implantation of AlloDerm, Strattice, decellularized rat muscle, or decellularized rat dermis to 30 or 60 days.

Decellularized Fetal Matrix Suppresses Fibrotic Gene Expression and Promotes Myogenesis in a Rat Model of Volumetric Muscle Loss.

Background: Traumatic muscle loss often results in poor functional restoration. Skeletal muscle injuries cannot be repaired without substantial fibrosis and loss of muscle function. Given its regenerative properties, the authors evaluated outcomes of fetal tissue-derived decellularized matrix for skeletal muscle regeneration.

Liposome-encapsulated statins reduce hypertrophic scarring through topical application.

Hypertrophic scar is an important clinical problem with limited therapeutic options. Aside from their roles as 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, statins have also been demonstrated to decrease scarring by reducing connective tissue growth factor (CTGF) expression. However, poor penetrative ability limits their utility as topical treatments for hypertrophic scar.

Artesunate inhibits myofibroblast formation via induction of apoptosis and antagonism of pro-fibrotic gene expression in human dermal fibroblasts.

The anti-malaria drug artesunate and other chemical analogs of artemisinin have demonstrated cytostatic and cytotoxic effects in bacterial and cancer cells. Artemisinin-derived compounds have also been demonstrated to attenuate fibrosis in preclinical animal models, but the mechanisms by which this inhibition occurs are not well-understood. We investigated the effects of artesunate on the emergence of the myofibroblast, which is causally implicated in pro-fibrotic pathologies.