Enhanced skin retention and permeation of a novel peptide via structural modification, chemical enhancement, and microneedles.

Hyperpigmentation is a common skin condition with serious psychosocial consequences. Decapeptide-12, a novel peptide, has been found to be safer than hydroquinone in reducing melanin content, with efficacy up to more than 50% upon 16 weeks of twice-daily treatment. However, the peptide suffers from limited transcutaneous penetration due to its hydrophilicity and high molecular weight.

Heterologous expression of mutated HLA-G1 reduces alloreactivity of human dermal fibroblasts.

Aim: To engineer a stable HLA-G molecule and evaluate its immunomodulatory properties in transgenic human dermal fibroblasts (HDFs).

Materials & Methods: A mutated HLA-G1 (mHLA-G1) molecule was generated by modifying the endoplasmic reticulum retrieval motif and 3'-untranslated region miRNA-binding sites of HLA-G1. Immunomodulatory properties of transgenic HDF-mHLA-G1 were evaluated in vitro.

Heterelogous expression of mutated HLA-G decreases immunogenicity of human embryonic stem cells and their epidermal derivatives.

Human embryonic stem cells (hESCs) are capable of extensive self-renewal and expansion and can differentiate into any somatic tissue, making them useful for regenerative medicine applications. Allogeneic transplantation of hESC-derived tissues from results in immunological rejection absent adjunctive immunosuppression. The goal of our study was to generate a universal pluripotent stem cell source by nucleofecting a mutated human leukocyte antigen G (mHLA-G) gene into hESCs using the PiggyBac transposon.

Inhibition of DNA methylation enhances HLA-G expression in human mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are immunosuppressive multipotent cells under investigation for potential therapeutic applications in regenerative medicine and prevention of graft-versus-host disease. Human leukocyte antigen (HLA)-G contributes to the immunomodulatory properties of MSCs. HLA-G expression in MSCs is very low and diminishes during in vitro expansion.

Human embryonic stem cell derived-mesenchymal stem cells: an alternative mesenchymal stem cell source for regenerative medicine therapy.

Aim: To enumerate and characterize mesenchymal stem cells (MSC) derived from human embryonic stem cells (hESC) for clinical application.

Materials & Methods: hESC were differentiated into hESC-MSC and characterized by the expression of surface markers using flow cytometry. hESC-MSC were evaluated with respect to growth kinetics, colony-forming potential, as well as osteogenic and adipogenic differentiation capacity.

Minireview: Peptide analogs and short sequence oligopeptides as modulators of skin pigmentation.

Short sequence amino acids or oligopeptides have recently garnered attention for use as treatments for a myriad of dermatologic disorders due to their ability to effect and modulate various biological processes in the epidermis and dermis, rendering them promising candidates as medical and cosmeceutical therapeutics. Major advantages include their relative ease of synthesis and multitude of modifications that can be applied to enhance potency, affinity, specificity, hydrophilicity or hydrophobicity and cytotoxicity. Given the photoprotective effects of eumelanin on skin, there has been substantial interest in developing agents, particularly α-MSH analogs, that can induce 'sunless tanning' helping reduce risk of melanoma and non-melanoma skin cancer.

Novel pentapeptide activators of mammalian and mushroom tyrosinase.

Melanoma incidence continues to rise due to intentional exposure to ultraviolet radiation (UVR) from sunlight and indoor tanning beds. Eumelanin exhibits photoprotective effects; thus, agents that induce its synthesis offer a means for sunless tanning without UVR damage. Herein, we report the development of two pentapeptides, P9 and P10, capable of enhancing melanin synthesis in B16 melanoma cells by activating mushroom and mouse tyrosinases without any effect on cell viability or proliferation.

Hydroquinone-induced depigmentation: case report and review of the literature.

Melasma is an acquired cutaneous disorder caused by an overproduction of melanin by the enzyme tyrosinase. Melasma remains a therapeutic challenge and no definitive standard therapy exists. Although hydroquinone (HQ) has emerged as the most common treatment, its popularity has recently waned because of concerns about its potential carcinogenicity and manufacturing challenges.

Mutated HLA-G3 localizes to the cell surface but does not inhibit cytotoxicity of natural killer cells.

HLA-G plays an important role in the induction of immune tolerance. Various attempts to produce good manufacturing practice levels of HLA-G as a therapeutic molecule have failed to date partly due to the complicated structure of full-length HLA-G1. Truncated HLA-G3 is simpler and easier to produce than HLA-G1 and contains the expected functional epitope in its only α1 monomorphic domain.

Temporal HLA profiling and immunomodulatory effects of human adult bone marrow- and adipose-derived mesenchymal stem cells.

Aim: To investigate the temporal HLA expression profile and immunomodulatory function of mesenchymal stem cells (MSCs) during in vitro expansion.

Materials & Methods: Adult bone marrow-derived MSCs (BMSCs) and adipose-derived MSCs (AMSCs) were cultured and HLA class I and II mRNA expression were investigated during serial expansion using semiquantitative reverse-transcription PCR. The immunomodulatory properties of MSCs were monitored using peripheral blood mononuclear cell (PBMC) proliferation and cytotoxicity assays.

Sign and pseudo-sign of Leser-Trélat: case reports and a review of the literature.

Background: Leser-Trélat is distinguished by a rare paraneoplastic sign that is characterized by the sudden eruption of multiple seborrheic keratoses (SKs), associated with underlying internal malignancies. Similar non-malignancy-associated SK eruptions are referred to as the "pseudo-sign of Leser-Trélat" (PLT).

Objective: Two cases of rapid SK eruptions, one the sign of Leser-Trélat (SLT) and one PLT, are presented, and the literature on SLT and PLT is reviewed.

Minimally invasive bipolar fractional radiofrequency treatment upregulates anti-senescence pathways.

Background: The sirtuin gene family has been implicated in various anti-senescence pathways. Its connection, if any, with the skin wound healing response has yet to be elucidated.

Objective: The goal of our study was to better understand the effects of FRF treatment on the sirtuin anti-senescence pathway in skin.

The expression and functional activity of membrane-bound human leukocyte antigen-G1 are influenced by the 3'-untranslated region.

Human Leukocyte Antigen (HLA)-G is an immunosuppressive molecule acting on both the innate and adaptive immune system. A 14 bp insertion/deletion polymorphism (rs66554220) in the 3'-untranslated region (3'UTR) of the HLA-G gene has been associated with a number of diseases, pregnancy complications, and graft rejection after organ transplantation. We have investigated the effect of HLA-G polymorphism in the 3'UTR on the processing and stability of the membrane-bound HLA-G1 (mHLA-G1) isoform, as well as its functional significance.

Isolation and cultivation of human scalp interfollicular epidermal stem cells.

Skin regeneration is intricately controlled by epidermal stem cells. In human skin, the long-lived, slow-cycling, and highly proliferative stem cells are located in the basal layer of the interfollicular epidermis (IFE). The ability to isolate and culture human IFE stem cells (IFESCs) offers fascinating therapeutic potential for skin diseases as well as epithelial tissue engineering.

Prospective multicenter clinical trial of a minimally invasive temperature-controlled bipolar fractional radiofrequency system for rhytid and laxity treatment.

Background: A minimally invasive fractional bipolar radiofrequency (FRF) was developed.

Objective: To evaluate safety and efficacy of FRF in reducing face and neck rhytides and laxity.

Materials And Methods: This prospective, open-label, multicenter clinical trial enrolled 100 subjects with mild to severe facial and neck rhytides and laxity at seven centers in a per-protocol analysis.

β2-Microglobulin-free HLA-G activates natural killer cells by increasing cytotoxicity and proinflammatory cytokine production.

Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class-I molecule and plays a role in tissue specific immunoregulation. Many studies have addressed functional aspects of β2-microglobulin (β2m)-associated HLA-G1. β2m-free HLA-G has been found in human placental cytotrophoblasts and pancreatic β cells although its function remains unclear.

Microdermabrasion: molecular mechanisms unraveled, part 1.

Microdermabrasion (MDA) remains a common in-office procedure for many dermatologic practices.The procedure offers minimal downtime with a low incidence of side effects, making it a relatively desirable option for skin rejuvenation. Investigators have identified many of the molecular mechanisms behind this technology in an attempt to optimize clinical results.

Microdermabrasion: molecular mechanisms unraveled, part 2.

Microdermabrasion (MDA) remains a common in-office procedure for many dermatologic practices. The procedure offers minimal downtime with a low incidence of side effects, making it a relatively desirable option for skin rejuvenation. Investigators have identified many of the molecular mechanisms behind this technology in an attempt to optimize clinical results.

Reassessment of HLA-G isoform specificity of MEM-G/9 and 4H84 monoclonal antibodies.

Human leukocyte antigen (HLA)-G is a non-classical HLA class I molecule thought to play a key role in maternal-fetal tolerance. Although initial studies suggested that HLA-G expression is restricted to extravillous cytotrophoblasts, expression was subsequently reported in a wide variety of other human tissues and tumor cells. However, consensus as to the validity of these collective findings has proven difficult because the antibodies used to define the temporal and spatial expression patterns of HLA-G remain incompletely characterized.

Full-length HLA-G1 and truncated HLA-G3 differentially increase HLA-E surface localization.

Human leukocyte antigen (HLA)-E plays a role in immune tolerance induction and its transport to the cell surface is limited and dependent on the availability of HLA class I signal peptide. The role of HLA-G in regulating HLA-E surface localization remains controversial. The aim of our study was to clarify whether full-length and truncated HLA-G isoforms regulate HLA-E surface localization.

Bioactive oligopeptides in dermatology: Part I.

Short sequence amino acids or oligopeptides represent a relatively new and promising area of dermatology. Oligopeptides are defined as peptide sequences ranging from 2 to 20 amino acids. This class of proteins includes potent biologically active compounds, which can modulate various cellular and molecular processes.

Bioactive oligopeptides in dermatology: Part II.

Peptides are central to the regulation and modulation of the chemical reactions and biological responses that occur in nature. Many physiological processes are affected by the interactions of these peptides, including cell proliferation and migration, inflammation, melanogenesis, angiogenesis and innate immunity. Thus, biologically active peptides offer a great potential medically and therapeutically.