Reduced cell cohesiveness of outgrowths from eccrine sweat glands delays wound closure in elderly skin

Human skin heals more slowly in aged vs. young adults, but the mechanism for this delay is unclear. In humans, eccrine sweat glands (ESGs) and hair follicles underlying wounds generate cohesive keratinocyte outgrowths that expand to form the new epidermis. Here, we compared the re‐epithelialization of partial‐thickness wounds created on the forearm of healthy young (< 40 yo) and aged (> 70 yo) adults. Our results confirm that the outgrowth of cells from ESGs is a major feature of repair in young skin. Strikingly, in aged skin, although ESG density is unaltered, less than 50% of the ESGs generate epithelial outgrowths during repair (vs. 100% in young). Surprisingly, aging does not alter the wound‐induced proliferation response in hair follicles or ESGs. Instead, there is an overall reduced cohesiveness of keratinocytes in aged skin. Reduced cell–cell cohesiveness was most obvious in ESG‐derived outgrowths that, when present, were surrounded by unconnected cells in the scab overlaying aged wounds. Reduced cell–cell contact persisted during the repair process, with increased intercellular spacing and reduced number of desmosomes. Together, reduced outgrowths of ESG (i) reduce the initial number of cells participating in epidermal repair, (ii) delay wound closure, and (iii) lead to a thinner repaired epidermis in aged vs. young skin. Failure to form cohesive ESG outgrowths may reflect impaired interactions of keratinocytes with the damaged ECM in aged skin. Our findings provide a framework to better understand the mediators of delayed re‐epithelialization in aging and further support the importance of ESGs for the repair of human wounds.     

Solid lipid nanoparticles for transdermal delivery of avanafil: optimization,formulation, in-vitro and ex-vivo studies

Context: Avanafil (AVA) is used in the treatment of erectile dysfunction, but is reported for its poor aqueous solubility. Solid lipid nanoparticles (SLNs) are lipid carriers that can greatly enhance drug solubility and bioavailability.

Objective: This work was aimed to formulate and optimize AVA SLNs with subsequent loading into hydrogel films for AVA transdermal delivery.

Materials and methods: AVA SLNs were prepared utilizing homogenization followed by ultra-sonication technique. The prepared SLNs were characterized for particle size, charge, surface morphology and drug content. The optimized SLNs formulation was incorporated into transdermal films prepared using HPMC and chitosan. Hydrogel films were evaluated for ex-vivo rat skin permeation using automated Franz diffusion cells. The permeation parameters and the release mechanism were evaluated. The transdermal permeation of the prepared AVA SLNs through the skin layers was studied using confocal laser scanning microscope.

Results: Lipid concentration and % of oil in lipid had a pronounced effect on particle size while, entrapment efficiency was significantly affected by lipid concentration and % of cholesterol. The optimized AVA SLNs showed particle size and entrapment efficiency of 86?nm and 85.01%, respectively. TEM images revealed spherecity of the particles. High permeation parameters were observed from HPMC films loaded with AVA SLNs. The release data were in favor of Higuchi diffusion model. The prepared AVA SLNs were able to penetrate deeper in skin layers.

Conclusion: HPMC transdermal film-loaded AVA SLNs is an effective and alternative to per-oral drug administration.     

Conditioning pain stimulation does not affect itch induced by intra-epidermal histamine pricks but aggravates neurogenic inflammation in healthy volunteers

This study investigated whether itch induced by intra-epidermal histamine is subjected to modulation by a standardized conditioned pain modulation (CPM) paradigm in 24 healthy volunteers. CPM was induced by computer-controlled cuff pressure algometry and histamine was introduced to the volar forearm by skin prick test punctures. Moreover, neurogenic inflammation and wheal reactions induced by histamine and autonomic nervous system responses (heart rate variability and skin conductance) were monitored. CPM did not modulate the intensity of histamine-induced itch suggesting that pruriceptive signaling is not inhibited by pain-recruited endogenous modulation, however, CPM was found to aggravate histamine-induced neurogenic inflammation, likely facilitated by efferent sympathetic fibers.     

皮肤组织模型中吸收和散射系数对单线态氧发光特性的影响

构建由脂肪乳剂和墨水组成的皮肤组织模型,定量研究皮肤组织模型的吸收系数μa和散射系数μs对光敏化单线态氧(singlet oxygen,~1O_2)发光特性的影响。利用~1O_2发光检测系统测量含光敏剂四硫磺基酞菁氯化铝的皮肤组织模型分别在中心波长为1 230,1 270和1 310 nm处的时间分辨发光光谱,对扣除背景信号后的时间分辨~1O_2发光光谱进行积分和拟合,获得~1O_2发光积分强度以及激发三重态寿命τ_T和~1O_2寿命τ_D。结果表明在皮肤组织模型中,~1O_2发光积分强度随着μ_a和μ_s的增大而减小,μ_a对τ_T和τ_D没有影响。τ_T随着μs的增加而增加,τ_D随μ_s的增加先骤降而后缓慢上升。当μ_a1.5 mm~(-1)和μ_s32 cm~(-1)时,~1O_2发光积分强度和τ_T、τ_D均趋于稳定,其中τ_T和τ_D分别为3.4±0.6μs和3.3±0.7μs。     

Mating games squid play: reproductive behaviour and sexual skin displays in Caribbean reef squid Sepioteuthis sepioidea

Observation of the sexual interactions of Sepioteuthis sepioidea squid during the short reproductive stage of their lives showed a scramble competition system, with both male and female polygyny. Mature females were faithful to a specific location in the daytime, whereas males moved from group to group and formed short-term consortships with females. Males defended females from other males, particularly with an agonistic Zebra display. Male–female pairs exchanged Saddle-Stripe displays, after which males might display an on–off Flicker. There was considerable female choice. Only if a female responded to this display with a parallel Rocking action would she pair and would the male deposit spermatophores at the base of her arms, and only 50% of the time did females move the spermatophores internally to where sperm might be released and stored in the oviducal gland for later fertilization of eggs. This long-term set of interactions and solitary deposition of hidden egg strings contrasts with the attraction of both sexes to a common ‘egg mop’ laid by many females which was a site of competition in other loliginid squid. Since Sepioteuthis is a primitive genus within the family Loliginidae, it may represent a generalist reproductive strategy that evolved into a specialized localization one.     

Differential Expression of microRNAs and their Regulatory Networks in Skin Tissue of Liaoning Cashmere Goat during Hair Follicle Cycles

MicroRNAs (miRNAs) are endogenous small noncoding RNA molecules that negatively regulate gene expression. Herein, we investigated a selective number of miRNAs for their expression in skin tissue of Liaoning Cashmere goat during hair follicle cycles, and their intracellular regulatory networks were constructed based on bioinformatics analysis. The relative expression of six miRNAs (mir-103-3p, -15b-5p, 17-5p, -200b, -25-3p, and -30c-5p) at anagen phase is significantly higher than that at catagen and/or telogen phases. In comparison to anagen, the relative expression of seven miRNAs (mir-148a-3p, -199a-3p, -199a-5p, -24-3p, -30a-5p, -30e-5p, and -29a-3p) was revealed to be significantly up-regulated at catagen and/or telogen stages. The network analyses of miRNAs indicated those miRNAs investigated might be directly or indirectly involved in several signaling pathways through their target genes. These results provided a foundation for further insight into the roles of these miRNAs in skin tissue of Liaoning Cashmere goat during hair follicle cycles.     

Immunohistochemical localization of irisin in skin,eye, and thyroid and pineal glands of the crested porcupine (Hystrix cristata)

Irisin was first identified in muscle cells. We detected irisin immunoreactivity in various organs of the crested porcupine (Hystrix cristata). In the epidermis, irisin immunoreactivity was localized mainly in stratum basale, stratum spinosum and stratum granulosum layers; immunoreactivity was not observed in the stratum corneum. In the dermis, irisin was found in the external and internal root sheath, cortex and medulla of hair follicles, and in sebaceous glands. Irisin immunoreactivity was found in the neural retina and skeletal muscle fibers associated with the eye. The pineal and thyroid glands also exhibited irisin immunoreactivity.     

Pistacia lentiscus fruit oil reduces oxidative stress in human skin explants caused by hydrogen peroxide

We investigated the efficacy of Pistacia lentiscus fruit oil (PLFO) for protecting human skin from damage due to oxidative stress. PLFO contains natural antioxidants including polyphenols, sterols and tocopherols. We compared the antioxidant potential of PLFO with extra virgin olive oil (EVOO). Explants of healthy adult human skin were grown in culture with either PLFO or EVOO before adding hydrogen peroxide (H₂O₂). We also used cultured skin explants to investigate the effects of PLFO on lipid oxidation and depletion of endogenous antioxidant defense enzymes including glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) one day after 2 h exposure to H₂O₂. We found that PLFO scavenged radicals and protected skin against oxidative injury. PLFO exhibited greater antioxidant and free radical scavenging activity than EVOO. Skin explants treated with PLFO inhibited H₂O₂ induced MDA formation by inhibition of lipid oxidation. In addition, the oil inhibited H₂O₂ induced depletion of antioxidant defense enzymes including GPx, SOD and CAT. We found that treatment with PLFO repaired skin damage owing to its antioxidant properties.     

A curated gene list for expanding the horizons of pigmentation biology

Over the past century, studies of human pigmentary disorders along with mouse and zebrafish models have shed light on the many cellular functions associated with visible pigment phenotypes. This has led to numerous genes annotated with the ontology term “pigmentation” in independent human, mouse, and zebrafish databases. Comparisons among these datasets revealed that each is individually incomplete in documenting all genes involved in integument‐based pigmentation phenotypes. Additionally, each database contained inherent species‐specific biases in data annotation, and the term “pigmentation” did not solely reflect integument pigmentation phenotypes. This review presents a comprehensive, cross‐species list of 650 genes involved in pigmentation phenotypes that was compiled with extensive manual curation of genes annotated in OMIM, MGI, ZFIN, and GO. The resulting cross‐species list of genes both intrinsic and extrinsic to integument pigment cells provides a valuable tool that can be used to expand our knowledge of complex, pigmentation‐associated pathways.