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Pigmentation evolved in ancestral humans to protect against toxic, ultraviolet B irradiation, but the question remains: "what is being protected?" Because humans with dark pigmentation display a suite of superior epidermal functions in comparison with their more lightly pigmented counterparts, we hypothesized and provided evidence that dark pigmentation evolved in Africa to support cutaneous function. Because our prior clinical studies also showed that a restoration of a competent barrier dampens cutaneous inflammation, we hypothesized that resistance to inflammation could have provided pigmented hominins with yet another, important evolutionary benefit. We addressed this issue here in two closely related strains of hairless mice, endowed with either moderate (Skh2/J) or absent (Skh1) pigmentation. In these models, we showed that (a) pigmented mice display a markedly reduced propensity to develop inflammation after challenges with either a topical irritant or allergen in comparison with their nonpigmented counterparts; (b) visible and histologic evidence of inflammation was paralleled by reduced levels of pro-inflammatory cytokines (i.e., IL-1α and INFα); (c) because depigmentation of Skh2/J mouse skin enhanced both visible inflammation and pro-inflammatory cytokine levels after comparable pro-inflammatory challenges, the reduced propensity to develop inflammation was directly linked to the presence of pigmentation; and (d) furthermore, in accordance with our prior work showing that pigment production endows benefits by reducing the surface pH of skin, acidification of albino (Skh1) mouse skin also protected against inflammation, and equalized cytokine levels to those found in pigmented skin. In summary, pigmentation yields a reduced propensity to develop inflammation, consistent with our hypothesis that dark pigmentation evolved in ancestral humans to provide a suite of barrier-linked benefits that now include resistance to inflammation.

The primary function of the skin is to form a mechanical, permeability, antimicrobial, and ultraviolet radiation barrier, which is essential for maintaining physiological homeostasis. Our previous studies demonstrated that cutaneous pigmentation could promote skin barrier function in addition to providing anti‐ultraviolet irradiation defense. The present study aimed to develop a new regimen that enhances skin barrier function by regulating skin pigmentation using low‐concentration imiquimod. Results showed that topical application of low‐concentration imiquimod effectively induced skin hyperpigmentation in the dorsal skin and external ear of mice without inducing inflammatory cell infiltration. An in vitro study also revealed that low‐concentration imiquimod did not induce any cytotoxic effects on melanoma cells but triggered excessive melanin synthesis. In coculture systems, low‐concentration imiquimod was noted to increase tyrosinase activity in a broader cellular context, revealing the potential role of neighboring cells in melanin production. The next‐generation sequencing result indicated that PKCη and Dnm3 might regulate melanin synthesis and release during imiquimod treatment. Overall, our study presents new insights into the regulation of melanin production by low‐concentration imiquimod, both in a mice model and cultured cells. Furthermore, our study highlights the potential benefits of imiquimod in promoting melanin synthesis without causing skin disruptions or inducing inflammation, validating its potential to serve as a method for enhancing skin barrier functions by regulating the epidermal melanization reaction. [ABSTRACT FROM AUTHOR]

Acute psychological stress (PS) mobilizes metabolic responses that are of immediate benefit to the host, but the current medical paradigm holds that PS exacerbates systemic and cutaneous inflammatory disorders. Although the adverse consequences of PS are usually attributed to neuroimmune mechanisms, PS also stimulates an increase in endogenous glucocorticoids (GCs) that compromises permeability barrier homeostasis, stratum corneum cohesion, wound healing, and epidermal innate immunity in normal skin. Yet, if such PS-induced increases in GC were uniformly harmful, natural selection should have eliminated this component of the stress response. Hence, we hypothesized here instead that stress-induced elevations in endogenous GC could benefit, rather than aggravate, cutaneous function and reduce inflammation in three immunologically diverse mouse models of inflammatory diseases. Indeed, superimposed exogenous (motion-restricted) stress reduced, rather than aggravated inflammation and improved epidermal function in all three models, even normalizing serum IgE levels in the atopic dermatitis model. Elevations in endogenous GC accounted for these apparent benefits, because coadministration of mifepristone prevented stress-induced disease amelioration. Thus, exogenous stress can benefit rather than aggravate cutaneous inflammatory dermatoses through the anti-inflammatory activity of increased endogenous GC.

Humans with darkly pigmented skin display superior permeability barrier function in comparison with humans with lightly pigmented skin. The reduced pH of the stratum corneum (SC) of darkly pigmented skin could account for enhanced function, because acidifying lightly pigmented human SC resets barrier function to darkly pigmented levels. In SKH1 (nonpigmented) versus SKH2/J (pigmented) hairless mice, we evaluated how a pigment-dependent reduction in pH could influence epidermal barrier function. Permeability barrier homeostasis is enhanced in SKH2/J versus SKH1 mice, correlating with a reduced pH in the lower SC that colocalizes with the extrusion of melanin granules. Darkly pigmented human epidermis also shows substantial melanin extrusion in the outer epidermis. Both acute barrier disruption and topical basic pH challenges accelerate reacidification of SKH2/J (but not SKH1) SC, while inducing melanin extrusion. SKH2/J mice also display enhanced expression of the SC acidifying enzyme, secretory phospholipase A2f (sPLA2f). Enhanced barrier function of SKH2/J mice could be attributed to enhanced activity of two acidic pH-dependent, ceramide-generating enzymes, β-glucocerebrosidase and acidic sphingomyelinase, leading to accelerated maturation of SC lamellar bilayers. Finally, organotypic cultures of darkly pigmented human keratinocytes display enhanced barrier function in comparison with lightly pigmented cultures. Together, these results suggest that the superior barrier function of pigmented epidermis can be largely attributed to the pH-lowering impact of melanin persistence/extrusion and enhanced sPLA2f expression.

The beneficial effects of certain herbal medicines on cutaneous function have been appreciated for centuries. Among these agents, chrysanthemum extract, apigenin, has been used for skin care, particularly in China, for millennia. However, the underlying mechanisms by which apigenin benefits the skin are not known. In this study, we first determined whether topical apigenin positively influences permeability barrier homoeostasis, and then the basis thereof. Hairless mice were treated topically with either 0.1% apigenin or vehicle alone twice daily for 9 days. At the end of the treatments, permeability barrier function was assessed with either an electrolytic water analyzer or a Tewameter. Our results show that topical apigenin significantly enhanced permeability barrier homoeostasis after tape stripping, although basal permeability barrier function remained unchanged. Improved barrier function correlated with enhanced filaggrin expression and lamellar body production, which was paralleled by elevated mRNA levels for the epidermal ABCA12. The mRNA levels for key lipid synthetic enzymes also were upregulated by apigenin. Finally, both cathelicidin-related peptide and mouse beta-defensin 3 immunostaining were increased by apigenin. We conclude that topical apigenin improves epidermal permeability barrier function by stimulating epidermal differentiation, lipid synthesis and secretion, as well as cutaneous antimicrobial peptide production. Apigenin could be useful for the prevention and treatment of skin disorders characterized by permeability barrier dysfunction, associated with reduced filaggrin levels and impaired antimicrobial defenses, such as atopic dermatitis.

Corneocyte desquamation has been ascribed to the following: 1) proteolytic degradation of corneodesmosomes (CDs); 2) disorganization of extracellular lamellar bilayers; and/or 3) "swell-shrinkage-slough" from hydration/dehydration. To address the cellular basis for normal exfoliation, we compared changes in lamellar bilayer architecture and CD structure in D-Squame strips from the first versus fifth stripping ("outer" vs. "mid"-stratum corneum (SC), respectively) from nine normal adult forearms. Strippings were either processed for standard electron microscopy (EM) or for ruthenium-, or osmium-tetroxide vapor fixation, followed by immediate epoxy embedment, an artifact-free protocol, which, to our knowledge, is previously unreported. CDs are largely intact in the mid-SC, but replaced by electron-dense (hydrophilic) clefts (lacunae) that expand laterally, splitting lamellar arrays in the outer SC. Some undegraded desmoglein 1/desmocollin 1 redistribute uniformly into corneocyte envelopes (CEs) in the outer SC (shown by proteomics, Z-stack confocal imaging, and immunoEM). CEs then thicken, likely facilitating exfoliation by increasing corneocyte rigidity. In vapor-fixed images, hydration only altered the volume of the extracellular compartment, expanding lacunae, further separating membrane arrays. During dehydration, air replaced water, maintaining the expanded extracellular compartment. Hydration also provoked degradation of membranes by activating contiguous acidic ceramidase activity. Together, these studies identify several parallel mechanisms that orchestrate exfoliation from the surface of normal human skin.

Plant oils have been utilized for a variety of purposes throughout history, with their integration into foods, cosmetics, and pharmaceutical products. They are now being increasingly recognized for their effects on both skin diseases and the restoration of cutaneous homeostasis. This article briefly reviews the available data on biological influences of topical skin applications of some plant oils (olive oil, olive pomace oil, sunflower seed oil, coconut oil, safflower seed oil, argan oil, soybean oil, peanut oil, sesame oil, avocado oil, borage oil, jojoba oil, oat oil, pomegranate seed oil, almond oil, bitter apricot oil, rose hip oil, German chamomile oil, and shea butter). Thus, it focuses on the therapeutic benefits of these plant oils according to their anti-inflammatory and antioxidant effects on the skin, promotion of wound healing and repair of skin barrier. [ABSTRACT FROM AUTHOR]

Male sterility has been widely used in hybrid seed production in Brassica, but not in B. rapa ssp. chinensis , and genetic models of male sterility for this subspecies are unclear. We discovered a spontaneous mutant in B. rapa ssp. chinensis A series of progeny tests indicated that male sterility in B. rapa ssp. chinensis follows a three-allele model with BrMs a , BrMs b , and BrMs c The male sterility locus has been mapped to chromosome A07 in BC 1 and F 2 populations through genotyping by sequencing. Fine mapping in a total of 1,590 F 2 plants narrowed the male sterility gene BrMs to a 400 kb region, with two SNP markers only 0.3 cM from the gene. Comparative gene mapping shows that the Ms gene in B. rapa ssp. pekinensis is different from the BrMs gene of B. rapa ssp. chinensis , despite that both genes are located on chromosome A07. Interestingly, the DNA sequence orthologous to a male sterile gene in Brassica napus , BnRf , is within 400 kb of the BrMs locus. The BnRf orthologs of B. rapa ssp. chinensis were sequenced, and one KASP marker (BrMs_indel) was developed for genotyping based on a 14 bp indel at intron 4. Cosegregation of male sterility and BrMs_indel genotypes in the F 2 population indicated that BnRf from B. napus and BrMs from B. rapa are likely to be orthologs. The BrMs_indel marker developed in this study will be useful in marker-assisted selection for the male sterility trait., (Copyright © 2020 Lin et al.)

The neutral lipids existing in the intercellular spaces of the stratum corneum (SC) provide a permeability barrier to prevent water loss. Nile red is the most sensitive lipid stain for tissue sections. However, due to the extremely flattened morphology of corneocytes and the resolution limits of the light microscope, Nile red staining is seldom used as a fluorescent probe for the lipid-rich SC. In this study, we modified the traditional method for visualization of intracellular lipid by adding 4% potassium hydroxide after Nile red staining. This modified method not only allowed visualization of lipids existing in the intercellular membrane regions and the lateral junctions of the adjoining corneocytes, but also clearly demonstrated small lipid droplets within pathological corneocytes. These features were not observed with the traditional staining method. Thus, this modified Nile red staining method greatly improved the resolution of the SC lipids under light microscopy and should be useful for studying lipid depositions in both normal and pathological SC.

Widespread bullous fixed drug eruption (FDE) is the most severe form of FDE and may be mistaken clinically for Stevens-Johnson syndrome or toxic epidermal necrolysis (SJS/TEN). We report two cases of generalized bullous drug eruption with extensive epidermal necrosis and detachment mimicking SJS/TEN overlap and TEN, respectively. The first patient, a 78-year-old man, developed SJS/TEN-like eruption with widespread dusky red patches and denuded areas shortly after taking multiple nonsteroidal antiinflammatory drugs (NSAIDs). Histopathology showed vacuolar interface dermatitis with numerous necrotic keratinocytes and a superficial and deep perivascular infiltrate containing lymphocytes, eosinophils, neutrophils and melanophages. These findings are consistent with FDE. The second patient, a 61-year-old woman, had three episodes of near-total body epidermal detachment shortly after taking NSAIDs. TEN was diagnosed clinically in all three episodes without pathologic confirmation. FDE was suspected due to lack of involvement of two mucosal sites and uneventful recovery. These cases highlight the importance of considering severe bullous FDE in the differential diagnosis of SJS and TEN, and the necessity of skin biopsy in such cases.

Growing evidence shows alopecia areata (AA) to be a T cell-mediated organ-specific autoimmune disease. This study aimed to evaluate the efficacy of high-dose steroid pulse therapy in Taiwanese patients with severe widespread AA exceeding 40% of the scalp. A total of 17 Taiwanese patients with severe AA lasting less than 2 years were treated once monthly at the outpatient clinic for six sessions. Children younger than 12 years of age received oral prednisolone (5 mg/kg) in three divided doses, while for adults, 500 mg methylprednisolone was infused intravenously over 2 hours. Patients with multifocal AA exhibited the most favorable response, with more than 75% hair regrowth (9/11). Relapse occurred in two patients at 4 and 8 months after the last treatment, respectively. One patient with ophiatic AA showed a transient response, but subsequently lost hair even upon continuation of therapy. Two patients of four with alopecia totalis had full hair regrowth but one lost hair again 6 months later. In the only patient with alopecia universalis, less than 10% hair regrowth occurred. No major side effects were observed. In summary, 11 of 17 patients (64.7%) had more than 75% hair regrowth after steroid pulse therapy. Our results indicated that steroid pulse therapy, given at 5-10 mg/kg once monthly for an average of 6 months, is effective and well tolerated in Taiwanese patients with severe multifocal AA lasting less than 2 years.