Traumatic Brain Injury Induces Early Barrier Protective Responses in Incisional Skin Wounds Accelerating Cutaneous Wound Healing.

Though Traumatic Brain Injury (TBI) and skin trauma often occur together, it is unresolved whether TBI changes the healing of skin wounds. We here explored whether TBI impacts the sequence of events during skin wound healing. Incisional skin wounds from mice subjected to TBI were assessed employing unbiased transcriptome analysis and immunostaining.

FluMag-SELEX derived specific individual aptamers can fluorescently label the ageing immanent protein-crosslinker glucosepane in diabetic mouse tissues.

Nowadays, aptamers have transitioned into valuable antibody alternatives. We present the first anti-glucosepane aptamer targeting a key glycation product linked to aging and diabetes. Glu3, with high specificity and affinity, enabled the first-ever direct, fluorescence-based histological staining of glucosepane in murine tissue, distinguishing diabetic samples from wild-type samples without secondary reagents.

Imbalanced redox dynamics induce fibroblast senescence leading to impaired stem cell pools and skin aging.

Skin function depends on a meticulously regulated dynamic interaction of distinct skin compartments such as the epidermis and dermis. Adaptive responses at the molecular and cellular level are essential for these interactions - and if dysregulated - drive skin aging and other pathologies. After defining the role of redox homeodynamics in physiology and aging pathology, we focus on the redox distress-dependent aging of dermal fibroblasts including their progenitors.

The skin of the naked mole-rat and its resilience against aging and cancer.

The naked mole-rat (NMR) Heterocephalus glaber (from the Greek/latin words ἕτερος, heteros = divergent, κεφαλή, kephalē = head and glabra = hairless) was first described by Rüppell (Fig. 1) and belongs to the Hystricognath (from the Greek words ὕστριξ, hystrix = porcupine and γνάθος, gnathos = jaw) as a suborder of rodents. NMR are characterized by the highest longevity among rodents and reveal a profound cancer resistance.

The weakness of senescent dermal fibroblasts.

Skin is the largest human organ with easily noticeable biophysical manifestations of aging. As human tissues age, there is chronological accumulation of biophysical changes due to internal and environmental factors. Skin aging leads to decreased elasticity and the loss of dermal matrix integrity via degradation.

Persistent JunB activation in fibroblasts disrupts stem cell niche interactions enforcing skin aging.

Fibroblasts residing in the connective tissues constitute the stem cell niche, particularly in organs such as skin. Although the effect of fibroblasts on stem cell niches and organ aging is an emerging concept, the underlying mechanisms are largely unresolved. We report a mechanism of redox-dependent activation of transcription factor JunB, which, through concomitant upregulation of p16 and repression of insulin growth factor-1 (IGF-1), initiates the installment of fibroblast senescence.

Transduction Enhancers Enable Efficient Human Adenovirus Type 5-Mediated Gene Transfer into Human Multipotent Mesenchymal Stromal Cells.

Human multipotent mesenchymal stromal cells (hMSCs) are currently developed as cell therapeutics for different applications, including regenerative medicine, immune modulation, and cancer treatment. The biological properties of hMSCs can be further modulated by genetic engineering. Viral vectors based on human adenovirus type 5 (HAdV-5) belong to the most frequently used vector types for genetic modification of human cells in vitro and in vivo.

Natural SIRT1 modifiers as promising therapeutic agents for improving diabetic wound healing.

Background: The occurrence of chronic wounds, account for significant suffering of diabetic people, together with increasing healthcare burden. The chronic wounds associated with diabetes do not undergo the normal healing process rather stagnate into chronic proinflammatory phase as well as declined fibroblast function and impaired cell migration.

Hypothesis: SIRT1, which is the most studied isoform of the sirtuin family in mammals, has now emerged as a crucial target for improving diabetic wound healing.

TLR4-dependent shaping of the wound site by MSCs accelerates wound healing.

We here address the question whether the unique capacity of mesenchymal stem cells to re-establish tissue homeostasis depends on their potential to sense pathogen-associated molecular pattern and, in consequence, mount an adaptive response in the interest of tissue repair. After injection of MSCs primed with the bacterial wall component LPS into murine wounds, an unexpected acceleration of healing occurs, clearly exceeding that of non-primed MSCs. This correlates with a fundamental reprogramming of the transcriptome in LPS-treated MSCs as deduced from RNAseq analysis and its validation.

MSCs rescue impaired wound healing in a murine LAD1 model by adaptive responses to low TGF-β1 levels.

Mutations in the CD18 gene encoding the common β-chain of β2 integrins result in impaired wound healing in humans and mice suffering from leukocyte adhesion deficiency syndrome type 1 (LAD1). Transplantation of adipose tissue-derived mesenchymal stem cells (MSCs) restores normal healing of CD18 wounds by restoring the decreased TGF-β1 concentrations. TGF-β1 released from MSCs leads to enhanced myofibroblast differentiation, wound contraction, and vessel formation.

Iron and iron-dependent reactive oxygen species in the regulation of macrophages and fibroblasts in non-healing chronic wounds.

Chronic wounds pose a stern challenge to health care systems with growing incidence especially in the aged population. In the presence of increased iron concentrations, recruitment of monocytes from the circulation and activation towards ROS and RNS releasing M1 macrophages together with the persistence of senescent fibroblasts at the wound site are significantly enhanced. This unrestrained activation of pro-inflammatory macrophages and senescent fibroblasts has increasingly been acknowledged as main driver causing non-healing wounds.

JunB defines functional and structural integrity of the epidermo-pilosebaceous unit in the skin.

Transcription factors ensure skin homeostasis via tight regulation of distinct resident stem cells. Here we report that JunB, a member of the AP-1 transcription factor family, regulates epidermal stem cells and sebaceous glands through balancing proliferation and differentiation of progenitors and by suppressing lineage infidelity. JunB deficiency in basal progenitors results in a dermatitis-like syndrome resembling seborrheic dermatitis harboring structurally and functionally impaired sebaceous glands with a globally altered lipid profile.

Author Correction: A Novel S100A8/A9 Induced Fingerprint of Mesenchymal Stem Cells associated with Enhanced Wound Healing.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

A Novel S100A8/A9 Induced Fingerprint of Mesenchymal Stem Cells associated with Enhanced Wound Healing.

We here investigated whether the unique capacity of mesenchymal stem cells (MSCs) to re-establish tissue homeostasis depends on their potential to sense danger associated molecular pattern (DAMP) and to mount an adaptive response in the interest of tissue repair. Unexpectedly, after injection of MSCs which had been pretreated with the calcium-binding DAMP protein S100A8/A9 into murine full-thickness wounds, we observed a significant acceleration of healing even exceeding that of non-treated MSCs. This correlates with a fundamental reprogramming of the transcriptome in S100A8/A9 treated MSCs as deduced from RNA-seq analysis and its validation.

A model of the onset of the senescence associated secretory phenotype after DNA damage induced senescence.

Cells and tissues are exposed to stress from numerous sources. Senescence is a protective mechanism that prevents malignant tissue changes and constitutes a fundamental mechanism of aging. It can be accompanied by a senescence associated secretory phenotype (SASP) that causes chronic inflammation.

Ribosomal transcription is regulated by PGC-1alpha and disturbed in Huntington's disease.

PGC-1α is a versatile inducer of mitochondrial biogenesis and responsive to the changing energy demands of the cell. As mitochondrial ATP production requires proteins that derive from translation products of cytosolic ribosomes, we asked whether PGC-1α directly takes part in ribosomal biogenesis. Here, we show that a fraction of cellular PGC-1α localizes to the nucleolus, the site of ribosomal transcription by RNA polymerase I.

Alpha-Ketoglutarate Curbs Differentiation and Induces Cell Death in Mesenchymal Stromal Precursors with Mitochondrial Dysfunction.

Increased concentrations of reactive oxygen species (ROS) originating from dysfunctional mitochondria contribute to diverse aging-related degenerative disorders. But so far little is known about the impact of distinct ROS on metabolism and fate of stromal precursor cells. Here, we demonstrate that an increase in superoxide anion radicals due to superoxide dismutase 2 (Sod2) deficiency in stromal precursor cells suppress osteogenic and adipogenic differentiation through fundamental changes in the global metabolite landscape.

Modelling safety of gantry crane operations using Petri nets.

Being a powerful tool in modelling industrial and service operations, Petri net (PN) has been extremely used in different domains, but its application in safety study is limited. In this study, we model the gantry crane operations used for industrial activities using generalized stochastic PNs. The complete cycle of operations of the gantry crane is split into three parts namely inspection and loading, movement of load, and unloading of load.

Superoxide anion radicals induce IGF-1 resistance through concomitant activation of PTP1B and PTEN.

The evolutionarily conserved IGF-1 signalling pathway is associated with longevity, metabolism, tissue homeostasis, and cancer progression. Its regulation relies on the delicate balance between activating kinases and suppressing phosphatases and is still not very well understood. We report here that IGF-1 signalling in vitro and in a murine ageing model in vivo is suppressed in response to accumulation of superoxide anions (O2∙-) in mitochondria, either by chemical inhibition of complex I or by genetic silencing of O2∙--dismutating mitochondrial Sod2.

The role of manganese superoxide dismutase in skin aging.

The free radical theory of aging postulates that the production of mitochondrial reactive oxygen species is the major determinant of aging and lifespan. The skin represents an excellent and accessible model organ to study aging that is characterized by atrophy, wrinkle formation, reduced tensile strength and impaired wound healing. Oxidative stress as a consequence of an imbalance in prooxidants and antioxidants with increased ROS concentrations has been demonstrated in the aged skin in vitro and in vivo, suggesting the important role of the antioxidant balance.

Accelerated aging phenotype in mice with conditional deficiency for mitochondrial superoxide dismutase in the connective tissue.

The free radical theory of aging postulates that the production of mitochondrial reactive oxygen species is the major determinant of aging and lifespan. Its role in aging of the connective tissue has not yet been established, even though the incidence of aging-related disorders in connective tissue-rich organs is high, causing major disability in the elderly. We have now addressed this question experimentally by creating mice with conditional deficiency of the mitochondrial manganese superoxide dismutase in fibroblasts and other mesenchyme-derived cells of connective tissues in all organs.