Investigation into the significant role of dermal-epidermal interactions in skin ageing utilising a bioengineered skin construct.

Increased prevalence of skin ageing is a growing concern due to an ageing global population and has both sociological and psychological implications. The use of more clinically predictive in vitro methods for dermatological research is becoming commonplace due to initiatives and the cost of clinical testing. In this study, we utilise a well-defined and characterised bioengineered skin construct as a tool to investigate the cellular and molecular dynamics involved in skin ageing from a dermal perspective.

Suppressed basal mitophagy drives cellular aging phenotypes that can be reversed by a p62-targeting small molecule.

Selective degradation of damaged mitochondria by autophagy (mitophagy) is proposed to play an important role in cellular homeostasis. However, the molecular mechanisms and the requirement of mitochondrial quality control by mitophagy for cellular physiology are poorly understood. Here, we demonstrated that primary human cells maintain highly active basal mitophagy initiated by mitochondrial superoxide signaling.

Transcriptomic analysis of human skin wound healing and rejuvenation following ablative fractional laser treatment.

Ablative fractional laser treatment is considered the gold standard for skin rejuvenation. In order to understand how fractional laser works to rejuvenate skin, we performed microarray profiling on skin biopsies to identify temporal and dose-response changes in gene expression following fractional laser treatment. The backs of 14 women were treated with ablative fractional laser (Fraxel®) and 4 mm punch biopsies were collected from an untreated site and at the treated sites 1, 3, 7, 14, 21 and 28 days after the single treatment.

Combinations of peptides synergistically activate the regenerative capacity of skin cells in vitro.

Objective: To explore synergistic effects related to skin regeneration, peptides with distinct biological mechanisms of action were evaluated in combination with different skin cell lines in the presence or absence of niacinamide (Nam). Furthermore, the synergistic responses of peptide combinations on global gene expression were compared with the changes that occur with fractional laser resurfacing treatment, a gold standard approach for skin rejuvenation, to further define optimal peptide combinations.

Methods: Microarray profiling was used to characterize the biological responses of peptide combinations (+/- Nam) relative to the individual components in epidermal keratinocyte and dermal fibroblast cell lines.

Reductive Stress Selectively Disrupts Collagen Homeostasis and Modifies Growth Factor-independent Signaling Through the MAPK/Akt Pathway in Human Dermal Fibroblasts.

Redox stress is a well-known contributor to aging and diseases in skin. Reductants such as dithiothreitol (DTT) can trigger a stress response by disrupting disulfide bonds. However, the quantitative response of the cellular proteome to reductants has not been explored, particularly in cells such as fibroblasts that produce extracellular matrix proteins.

Incubatory environment of the scalp impacts pre-emergent hair to affect post-emergent hair cuticle integrity.

Objectives: To determine whether the oxidative stress transmitted to newly grown hair from an unhealthy scalp has physical consequences to the cuticular condition and function.

Methods: A uniquely designed 24-week clinical study included 8 weeks of pretreatment with a cosmetic shampoo and 16 weeks of treatment with either a potentiated zinc pyrithione (ZPT) antidandruff shampoo or a placebo cosmetic shampoo. This clinical design allowed the growth and acquisition of hair samples under conditions of varying but known scalp health as a result of treating a dandruff/seborrheic dermatitis (D/SD) population.

Advanced hair damage model from ultra-violet radiation in the presence of copper.

Objective: Damage to hair from UV exposure has been well reported in the literature and is known to be a highly complex process involving initiation via absorption of UV light followed by formation and propagation of reactive oxygen species (ROS). The objective of this work was to understand these mechanisms, explain the role of copper in accelerating the formation of ROS and identify strategies to reduce the hair damage caused by these reactive species.

Methods: The location of copper in hair was measured by Transmission electron microscopy-(TEM) X-ray energy dispersive spectroscopy (XEDS) and levels measured by ICP-OES.

Human hair shaft proteomic profiling: individual differences, site specificity and cuticle analysis.

Hair from different individuals can be distinguished by physical properties. Although some data exist on other species, examination of the individual molecular differences within the human hair shaft has not been thoroughly investigated. Shotgun proteomic analysis revealed considerable variation in profile among samples from Caucasian, African-American, Kenyan and Korean subjects.

Role of copper in photochemical damage to hair.

Objective: The objective of this work was to identify whether low levels of redox metals such as copper will accelerate damage to hair on exposure to UV irradiation and whether this damage can be prevented.

Methods: The methods used were proteomics to measure the protein damage via protein loss after different periods of exposure and mass spectroscopy methods to identify specific marker peptides that are specifically created by this type of damage.

Results: In this work, we have developed new insights into the mechanism of UV damage using these proteomic methods.

The role of chelants in controlling Cu(II)-induced radical chemistry in oxidative hair colouring products.

The catalytic formation of hydroxyl radicals in oxidative hair colourant systems in the presence of added copper ions was measured and quantified using a colorimetric probe N,N'-(5-nitro-1,3-phenylene)bisglutaramide. Also monitored in the same experiments was the decomposition of hydrogen peroxide. The first set of experiments was performed using aqueous model solutions containing the key oxidant actives in a hair colourant, ammonium hydroxide and hydrogen peroxide at pH 10, with added copper and calcium ions.

The proteomic profile of hair damage.

Background: Monilethrix is a congenital hair shaft disorder with associated fragility. Many of the changes seen in monilethrix hair on light microscopy and scanning electron microscopy are also seen in hair weathering and cosmetic damage to hair.

Objectives: We used monilethrix as a model to investigate the relationship between hair protein structure and hair strength and resistance to cosmetic insult.

Molecular basis of differential B-pentamer stability of Shiga toxins 1 and 2.

Escherichia coli strain O157:H7 is a major cause of food poisoning that can result in severe diarrhea and, in some cases, renal failure. The pathogenesis of E. coli O157:H7 is in large part due to the production of Shiga toxin (Stx), an AB(5) toxin that consists of a ribosomal RNA-cleaving A-subunit surrounded by a pentamer of receptor-binding B subunits.

Shiga toxin subtypes display dramatic differences in potency.

Purified Shiga toxin (Stx) alone is capable of producing systemic complications, including hemolytic-uremic syndrome (HUS), in animal models of disease. Stx includes two major antigenic forms (Stx1 and Stx2), with minor variants of Stx2 (Stx2a to -h). Stx2a is more potent than Stx1.

Comparison of binding platforms yields insights into receptor binding differences between shiga toxins 1 and 2.

Protein-glycan interactions are typically very weak, and avid binding is achieved when proteins express multiple glycan binding sites. Shiga toxin (Stx) uses glycan receptors to enter cells. Stx has five identical binding subunits, each with three nonidentical glycan binding sites.

Characterization of a two-component regulatory system from Acinetobacter baumannii that controls biofilm formation and cellular morphology.

Acinetobacter baumannii forms biofilms on abiotic surfaces, a phenotype that may explain its ability to survive in nosocomial environments and to cause device-related infections in compromised patients. The biofilm proficiency of the 19606 type strain depends on the production of pili, cell-surface appendages assembled via the CsuAB-A-B-C-D-E chaperone-usher secretion system. The screening of a bank of isogenic insertion derivatives led to the identification of a biofilm-deficient derivative in which a transposon insertion disrupted a gene predicted to encode the response regulator of a two-component regulatory system.

Comparative analysis of the abilities of Shiga toxins 1 and 2 to bind to and influence neutrophil apoptosis.

Hemolytic-uremic syndrome (HUS), the life-threatening complication following infection by the intestinal pathogen Escherichia coli O157:H7, is due to the ability of the pathogen to produce toxins in the Shiga toxin (Stx) family. Activated neutrophils are observed in HUS patients, yet it is unclear whether Stx exerts a direct effect on neutrophils or whether the toxin acts indirectly. The effect of Stx1 and Stx2 on human neutrophils was examined.