New Medical Herbalism Formulations as a Targeted Therapeutic Strategies Used in Southern Tunisia to Promote Neo-Epithelium, Angiogenesis, and Collagen Biosynthesis and to Impede Scar Formation Post-Third-Degree Burned Skin.

The aim of the study is to assess the suitability of the herbal formulation for topical application as a skin burn dressing on the in vivo wound-closure of third-degree wound injuries. Rat wound models were used to prove the in vivo skin burn-healing process. Body weight gain, food and water intake, and behavior were investigated daily during treatment period. Cutaneous biopsies of the burned wound surfaces were monitored at days 4, 13, and 28. Formulation markedly (P < .05) increased wound repair rate and collagen production compared to untreated burnt skin. Macroscopic and histological analysis of the wound of formula (F)-treated group showed significant skin contraction rate and rapid wound healing without scar through regeneration of epidermis that were approved in formula mixed with honey (F-hY)- and Drs-treated wound compared with thymol, and the untreated wound tissues that were not covered by denuded epithelial. Furthermore, the wound healing efficacy of F-hY, F, and Drs cream was proved by decreased the amount of malondialdehyde compared to untreated rats. In conclusion, F and F-hY was found to promote cutaneous wound repair. In all case, the formula alone or mixed with honeybees was even better than thymol in the repair of cutaneous wound.

Use of mouse primary epidermal organoids for USA300 infection modeling and drug screening.

Skin infections caused by drug-resistant Staphylococcus aureus occur at high rates nationwide. Mouse primary epidermal organoids (mPEOs) possess stratified histological and morphological characteristics of epidermis and are highly similar to their derived tissue at the transcriptomic and proteomic levels. Herein, the susceptibility of mPEOs to methicillin-resistant S. aureus USA300 infection was investigated. The results show that mPEOs support USA300 colonization and invasion, exhibiting swollen epithelial squamous cells with nuclear necrosis and secreting inflammatory factors such as IL-1ß. Meanwhile mPEOs beneficial to observe the process of USA300 colonization with increasing infection time, and USA300 induces mPEOs to undergo pyroptosis and autophagy. In addition, we performed a drug screen for the mPEO infection model and showed that vancomycin restores cell viability and inhibits bacterial internalization in a concentration-dependent manner. In conclusion, we establish an in vitro skin infection model that contributes to the examination of drug screening strategies and antimicrobial drug mechanisms.

Improving Dermal Delivery of Rose Bengal by Deformable Lipid Nanovesicles for Topical Treatment of Melanoma.

Cutaneous melanoma is one of the most aggressive and metastatic forms of skin cancer. However, current therapeutic options present several limitations, and the annual death rate due to melanoma increases every year. Dermal delivery of nanomedicines can effectively eradicate primary melanoma lesions, avoid the metastatic process, and improve survival. Rose Bengal (RB) is a sono-photosensitizer drug with intrinsic cytotoxicity toward melanoma without external stimuli but the biopharmaceutical profile limits its clinical use. Here, we propose deformable lipid nanovesicles, also known as transfersomes (TF), for the targeted dermal delivery of RB to melanoma lesions to eradicate them in the absence of external stimuli. Considering RB's poor ability to cross the stratum corneum and its photosensitizer nature, transfersomal carriers were selected simultaneously to enhance RB penetration to the deepest skin layers and protect RB from undesired photodegradation. RB-loaded TF dispersion (RB-TF), prepared by a modified reverse-phase evaporation method, were nanosized with a ζ-potential value below -30 mV. The spectrophotometric and fluorimetric analysis revealed that RB efficiently interacted with the lipid phase. The morphological investigations (transmission electron microscopy and small-angle X-ray scattering) proved that RB intercalated within the phospholipid bilayer of TF originating unilamellar and deformable vesicles, in contrast to the rigid multilamellar unloaded ones. Such outcomes agree with the results of the in vitro permeation study, where the lack of a burst RB permeation peak for RB-TF, observed instead for the free drug, suggests that a significant amount of RB interacted with lipid nanovesicles. Also, RB-TF proved to protect RB from undesired photodegradation over 24 h of direct light exposure. The ex vivo epidermis permeation study proved that RB-TF significantly increased RB's amount permeating the epidermis compared to the free drug (78.31 vs 38.31%). Finally, the antiproliferative assays on melanoma cells suggested that RB-TF effectively reduced cell growth compared to free RB at the concentrations tested (25 and 50 µM). RB-TF could potentially increase selectivity toward cancer cells. Considering the outcomes of the characterization and cytotoxicity studies performed on RB-TF, we conclude that RB-TF represents a valid potential alternative tool to fight against primary melanoma lesions via dermal delivery in the absence of light.

Histological Evidence of Wound Healing Improvement in Rats Treated with Oral Administration of Hydroalcoholic Extract of Vitis labrusca.

Plant extracts rich in phenolic compounds have been demonstrated to accelerate wound healing, but their use by oral route has been poorly studied. The leaves of Vitis labrusca are rich in phenolic acids and flavonoids. The goal of this study was to assess the healing properties of the oral administration of hydroalcoholic extract of V. labrusca leaves (HEVL) in a murine model. HEVL was obtained by Soxhlet and dynamic maceration, and their yield and phenolic acids and flavonoid contents were determined. For the wound healing assay, 8 mm wounds were performed on the back of 48 Wistar rats, assigned into four groups (n = 12): CTR (distilled water), HEVL100, HEVL200, and HEVL300 (HEVL at 100, 200, and 300 mg/kg, respectively). On days 7 and 14, wound closure rates were assessed, and the healing wounds were subjected to histological analysis. Soxhlet-obtained extract was selected for the wound healing assay because it provided a higher yield and phenolic acid and flavonoid contents. HEVL significantly reduced leukocytosis in the peripheral blood (p < 0.05), accelerated wound closure (p < 0.05), and improved collagenization (p < 0.05) on day 7, as well as enhanced the epidermal tissue thickness (p < 0.001) and elastic fiber deposition on day 14 (p < 0.01). Furthermore, HEVL promoted an increase in the histological grading of wound healing on both days 7 and 14 (p < 0.01). The doses of 200 and 300 mg/kg provided better results than 100 mg/Kg. Our data provide histological evidence that the oral administration of HEVL improves wound healing in rodents. Therefore, the extract can be a potential oral medicine for healing purposes.

Evaluation of Polymeric Matrix Loaded with Melatonin for Wound Dressing.

The development of scaffolds mimicking the extracellular matrix containing bioactive substances has great potential in tissue engineering and wound healing applications. This study investigates melatonin-a methoxyindole present in almost all biological systems. Melatonin is a bioregulator in terms of its potential clinical importance for future therapies of cutaneous diseases. Mammalian skin is not only a prominent melatonin target, but also produces and rapidly metabolizes the multifunctional methoxyindole to biologically active metabolites. In our methodology, chitosan/collagen (CTS/Coll)-contained biomaterials are blended with melatonin at different doses to fabricate biomimetic hybrid scaffolds. We use rat tail tendon- and Salmo salar fish skin-derived collagens to assess biophysical and cellular properties by (i) Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR), (ii) thermogravimetric analysis (TG), (iii) scanning electron microscope (SEM), and (iv) proliferation ratio of cutaneous cells in vitro. Our results indicate that melatonin itself does not negatively affect biophysical properties of melatonin-immobilized hybrid scaffolds, but it induces a pronounced elevation of cell viability within human epidermal keratinocytes (NHEK), dermal fibroblasts (NHDF), and reference melanoma cells. These results demonstrate that this indoleamine accelerates re-epithelialization. This delivery is a promising technique for additional explorations in future dermatotherapy and protective skin medicine.

Toxicological and anti-tumor effects of a linden extract (Tilia platyphyllos Scop.) in a HPV16-transgenic mouse model.

Tilia platyphyllos Scop. is a popular broad-leaved tree, native to Central and Southern Europe. Hydroethanolic extracts rich in phenolic compounds obtained from T. platyphyllos Scop. have shown in vitro antioxidant, anti-inflammatory and antitumor properties. The aim of this work was to evaluate the therapeutic properties of a hydroethanolic extract obtained from T. platyphyllos in HPV16-transgenic mice. The animals were divided into eight groups according to their sex and phenotype. Four groups of female: HPV+ exposed to linden (HPV linden; n = 6), HPV+ (HPV water; n = 4), HPV- exposed to linden (WT linden; n = 5) and HPV- (WT water; n = 4) and four groups of male: HPV+ exposed to linden (HPV linden; n = 5), HPV+ (HPV water; n = 5), HPV- exposed to linden (WT linden; n = 5) and HPV- (WT water; n = 7). The linden (Tilia platyphyllos Scop.) extract was orally administered at a dose of 4.5 mg/10 mL per animal (dissolved in water) and changed daily for 33 days. The hydroethanolic extract of T. platyphyllos consisted of protocatechuic acid and (-)-epicatechin as the most abundant phenolic acid and flavonoid, respectively, and was found to be stable during the studied period. In two male groups a significant positive weight gain was observed but without association with the linden extract. Histological, biochemical, and oxidative stress analyses for the evaluation of kidney and liver damage support the hypothesis that the linden extract is safe and well-tolerated under the present experimental conditions. Skin histopathology does not demonstrate the chemopreventive effect of the linden extract against HPV16-induced lesions. The linden extract has revealed a favourable toxicological profile; however, additional studies are required to determine the chemopreventive potential of the linden extract.

Herpes Simplex Virus type 1 infects Langerhans cells and the novel epidermal dendritic cell, Epi-cDC2s, via different entry pathways.

Skin mononuclear phagocytes (MNPs) provide the first interactions of invading viruses with the immune system. In addition to Langerhans cells (LCs), we recently described a second epidermal MNP population, Epi-cDC2s, in human anogenital epidermis that is closely related to dermal conventional dendritic cells type 2 (cDC2) and can be preferentially infected by HIV. Here we show that in epidermal explants topically infected with herpes simplex virus (HSV-1), both LCs and Epi-cDC2s interact with HSV-1 particles and infected keratinocytes. Isolated Epi-cDC2s support higher levels of infection than LCs in vitro, inhibited by acyclovir, but both MNP subtypes express similar levels of the HSV entry receptors nectin-1 and HVEM, and show similar levels of initial uptake. Using inhibitors of endosomal acidification, actin and cholesterol, we found that HSV-1 utilises different entry pathways in each cell type. HSV-1 predominantly infects LCs, and monocyte-derived MNPs, via a pH-dependent pathway. In contrast, Epi-cDC2s are mainly infected via a pH-independent pathway which may contribute to the enhanced infection of Epi-cDC2s. Both cells underwent apoptosis suggesting that Epi-cDC2s may follow the same dermal migration and uptake by dermal MNPs that we have previously shown for LCs. Thus, we hypothesize that the uptake of HSV and infection of Epi-cDC2s will stimulate immune responses via a different pathway to LCs, which in future may help guide HSV vaccine development and adjuvant targeting.

Anti-inflammatory Effect of Red Macroalgae Bulung Sangu (Gracilaria sp.) Extract in UVB-Irradiated Mice.

BACKGROUND AND OBJECTIVE: Bulung Sangu, like many other macroalgae, is a source of beneficial phytochemical for health. This study was aimed to determine the anti-inflammatory effect of bulung sangu ethanol extract cream. MATERIALS AND METHODS: The compounds of bulung sangu ethanol extract were identified by using gas chromatography. The antioxidant activity of the extract was examined by the DPPH assay. The anti-inflammatory effect was analyzed in vivo against ultraviolet B (UVB) induction through variables of epidermal thickening and epidermal erosion scores. RESULTS: Our results showed that bulung sangu ethanol extract contained 18 compounds, in which, 11 compounds considered active as antioxidant and/or anti-inflammatory. Cream extract in both concentrations showed scavenging for more than 50%, with a concentration of 10% cream extract exhibited higher antioxidant activity compared to 5%. The in vivo assay showed a reduction of epidermal thickness and epidermal erosion in the application of both concentrations. The concentration of 10% cream extract showed higher reduction compared to 5% with results produced resembling normal. CONCLUSION: It can be concluded that bulung sangu displayed a potential source for being developed for the health and medicine aspect, especially for various activities supported by antioxidants and anti-inflammatory.

Skin Penetration Enhancement Strategies Used in the Development of Melanoma Topical Treatments.

Malignant melanoma is an aggressive form of skin cancer for which there is currently no reliable therapy and is considered one of the leading health issues in the USA. At present, surgery is the most effective and acceptable treatment; however, surgical excision can be impractical in certain circumstances. Topical skin delivery of drugs using topical formulations is a potential alternative approach which can have many advantages aside from being a non-invasive delivery route. Nevertheless, the presence of the stratum corneum (SC) limits the penetration of drugs through the skin, lowering their treatment efficacy and raising concerns among physicians and patients as to their effectiveness. Currently, research groups are trying to circumvent the SC barrier by using skin penetration enhancement (SPE) strategies. The SPE strategies investigated include chemical skin penetration enhancers (CPEs), physical skin penetration enhancers (PPEs), nanocarrier systems, and a combination of SPE strategies (cream). Of these, PPEs and cream are the most advanced approaches in terms of preclinical and clinical studies, respectively.

Protective effects of a comprehensive topical antioxidant against ozone-induced damage in a reconstructed human skin model.

Tropospheric ozone (O3) is a source of oxidative stress. This study examined the ability of a topical antioxidant (WEL-DS) to inhibit O3-mediated damage in a human epidermal skin model. Four groups of tissues (N = 24) were compared: Group 1 (control) were untreated and unexposed; Group 2 were untreated and exposed to O3 (0.4 ppm, 4 h); Group 3 were pretreated with WEL-DS and unexposed; Group 4 were pretreated with WEL-DS and exposed to O3 (0.4 ppm, 4 h). Pretreated tissues were topically treated with 20 uL of WEL-DS and incubated for up to 20 h at 37 °C [humidified, 5% carbon dioxide (CO2)]. After 24 h, tissues were re-treated with WEL-DS and exposed to O3. Tissues were evaluated for Reactive Oxygen Species (ROS), hydrogen peroxide (H2O2), 4-hydroxynonenal (4-HNE) protein adducts, NF-κB p65 response and histology. In O3-exposed groups, WEL-DS significantly inhibited ROS formation vs. untreated tissues (p < 0.05). Pretreatment with WEL-DS inhibited H2O2 production vs. untreated tissues (p < 0.05), and decreased NF-κB p65 transcription factor signal. Oxidative stress induction in O3-exposed tissues was confirmed by increased levels of 4-HNE protein adducts (marker of lipid peroxidation); WEL-DS application reduced this effect. WEL-DS inhibited damage in tissues exposed to O3 with no significant changes in epidermal structure. A comprehensive topical antioxidant significantly diminished O3-induced oxidative damage in a human epidermal skin model.

Anti-Inflammatory, Barrier-Protective, and Antiwrinkle Properties of Agastache rugosa Kuntze in Human Epidermal Keratinocytes.

This work aimed to assess the skin-beneficial properties of Agastache rugosa Kuntze, an herbal medication used to treat different types of disorders in traditional folk medicine. The total phenolic compounds and total antiradical, nitrite scavenging, superoxide scavenging, antielastase, and antihyaluronidase activities of a hot water extract of A. rugosa Kuntze leaves (ARE) were spectrophotometrically determined. Intracellular reactive oxygen species (ROS) was fluorometrically quantitated using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). Inducible nitric oxide synthase (iNOS) and filaggrin were evaluated using Western analysis. Real-time quantitative RT-PCR was used to measure filaggrin mRNA. Caspase-14 activity was determined using a fluorogenic substrate. ARE contained the total phenolic content of 38.9 mg gallic acid equivalent/g extract and exhibited 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical, superoxide radical, and nitrite scavenging activities with the SC50 values of 2.9, 1.4, and 1.7 mg/mL, respectively. ARE exerted suppressive activities on nitric oxide (NO) and ROS levels elevated by lipopolysaccharide (LPS) or tumor necrosis factor-α (TNF-α) in HaCaT keratinocytes. It attenuated the LPS-stimulated expression of iNOS. ARE augmented the UV-B-reduced filaggrin expression on both protein and mRNA levels and was capable of upregulating the UV-B-reduced caspase-14 activity. ARE inhibited in vitro elastase and hyaluronidase activities associated with the wrinkling process. ARE, at the concentrations used, did not interfere with the viability of HaCaT keratinocytes. These findings preliminarily imply that the leaves of A. rugosa possess desirable cosmetic potentials, such as anti-inflammatory, barrier protective, and antiwrinkle activities, which infers their skin healing potentials.

Baccharis dracunculifolia (Asteraceae) essential oil displays anti-inflammatory activity in models of skin inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Baccharis dracunculifolia (Asteraceae) is a commonly used plant in traditional medicine known as "alecrim-do-campo". Popularly it has been used as an immunostimulant, antibiotic, anti-inflammatory among other applications. So far, only a few studies have investigated the B. dracunculifolia anti-inflammatory effect and none has investigated the effectiveness of essential oil on skin diseases. AIM OF THE STUDY: The study aimed at evaluating the topical anti-inflammatory activity of B. dracunculifolia essential oil (BdEO) in mice models of acute and chronic skin inflammation. MATERIALS AND METHODS: BdEO was obtained from leaves and it was analyzed with Gas Chromatograph. Topical anti-inflammatory activity of BdEO (0.1, 0.3 and 1.0 mg/ear) was evaluated in Arachidonic Acid or TPA-induced acute and chronic skin inflammation in mice. Parameters such edema, cell migration and keratinocytes proliferation were evaluated. In addition, safety and a possible mechanism of action for BdEO essential oil were also investigated. RESULTS: Our results indicate that mainly terpenoids compounds compose BdEO. In addition, topical treatment with BdEO inhibited inflammatory parameters in both acute and chronic models of skin inflammation. This protective effect was associated with reduced edema formation, smaller cellular influx into the inflamed tissue and reduction of keratinocytes hyperproliferation. Although BdEO appears to exert its anti-inflammatory effect through a corticosteroid pathway, no local or systemic side effects were observed. CONCLUSION: Taken together, the present results showed that the essential oil obtained by hydrodistillation from B. dracunculifolia leaf samples exhibit remarkable topical anti-inflammatory properties. Therefore, our study demonstrated evidence for BdEO topical anti-inflammatory efficacy and safety, suggesting that it could be considered for developing of a new phytotherapeutic formulation as treatment for skin diseases.

Metabolic and pathologic profiles of human LSS deficiency recapitulated in mice.

Skin lesions, cataracts, and congenital anomalies have been frequently associated with inherited deficiencies in enzymes that synthesize cholesterol. Lanosterol synthase (LSS) converts (S)-2,3-epoxysqualene to lanosterol in the cholesterol biosynthesis pathway. Biallelic mutations in LSS have been reported in families with congenital cataracts and, very recently, have been reported in cases of hypotrichosis. However, it remains to be clarified whether these phenotypes are caused by LSS enzymatic deficiencies in each tissue, and disruption of LSS enzymatic activity in vivo has not yet been validated. We identified two patients with novel biallelic LSS mutations who exhibited congenital hypotrichosis and midline anomalies but did not have cataracts. We showed that the blockade of the LSS enzyme reaction occurred in the patients by measuring the (S)-2,3-epoxysqualene/lanosterol ratio in the forehead sebum, which would be a good biomarker for the diagnosis of LSS deficiency. Epidermis-specific Lss knockout mice showed neonatal lethality due to dehydration, indicating that LSS could be involved in skin barrier integrity. Tamoxifen-induced knockout of Lss in the epidermis caused hypotrichosis in adult mice. Lens-specific Lss knockout mice had cataracts. These results confirmed that LSS deficiency causes hypotrichosis and cataracts due to loss-of-function mutations in LSS in each tissue. These mouse models will lead to the elucidation of the pathophysiological mechanisms associated with disrupted LSS and to the development of therapeutic treatments for LSS deficiency.

Chrysin alleviates imiquimod-induced psoriasis-like skin inflammation and reduces the release of CCL20 and antimicrobial peptides.

Psoriasis is a common non-contagious chronic inflammatory skin lesion, with frequent recurrence. It mainly occurs due to aberrant regulation of the immune system leading to abnormal proliferation of skin cells. However, the pathogenic mechanisms of psoriasis are not fully understood. Although most of the current therapies are mostly efficient, the side effects can result in therapy stop, which makes the effectiveness of treatment strategies limited. Therefore, it is urgent and necessary to develop novel therapeutics. Here, we investigated the efficacy of chrysin, a plant flavonoid, which we previously reported to possess strong antioxidant and anti-inflammatory effects, against psoriasis-like inflammation. Our results revealed that chrysin significantly attenuated imiquimod-induced psoriasis-like skin lesions in mice, and improved imiquimod-induced disruption of skin barrier. Moreover, the TNF-α, IL-17A, and IL-22-induced phosphorylation of MAPK and JAK-STAT pathways, and activation of the NF-κB pathway were also attenuated by chrysin pretreatment of epidermal keratinocytes. Most importantly, chrysin reduced TNF-α-, IL-17A-, and IL-22-induced CCL20 and antimicrobial peptide release from epidermal keratinocytes. Thus, our findings indicate that chrysin may have therapeutic potential against inflammatory skin diseases. Our study provides a basis for further investigating chrysin as a novel pharmacologic agent and contributes to the academic advancement in the field of Chinese herbal medicine.

Histology of ex vivo skin after treatment with fractionated picosecond Nd:YAG laser in high and low-energy settings.

Background: The fractionated picosecond laser produces microscopic lesions in the epidermis and dermis, which are known as laser-induced optical breakdown (LIOB) and intra-dermal laser-induced cavitation (LIC). There have been multiple histological reports on these phenomena, although some have been challenged on the grounds of similarity to artifacts. Asian skins, with a higher melanin content, may react differently to this treatment, and present literature is also lacking in this area.Purpose: To observe and report the histological effect of different energy levels and parameters of the fractional 532 nm/1064 nm picosecond laser on Asian skin ex vivo.Methods: Six skin samples were taken from clinically normal-looking perilesional areas and treated with different energy levels and parameters of the fractional 532 nm/1064 nm picosecond laser. The specimens were then sent to the lab for H&E staining, and the slides were reviewed by a dermatopathologist.Results: Superficial, intra-epidermal LIOBs were seen in skin treating at higher laser energies; deep, intra-dermal LICs were seen in skin treated at lower energies. Lesion sizes and depths were consistent with previously reported values on Caucasian skins, and lesions were spaced in 600-µm intervals or its multiple.Conclusions: The histological findings are consistent with results from other ethnicities, and the spacing of lesions is a strong indication of their validity as LIOBs or LICs.

Prospective, preclinical comparison of the performance between radiofrequency microneedling and microneedling alone in reversing photoaged skin.

BACKGROUND: There is a tremendous demand for dermal rejuvenation with minimal invasiveness and patient downtime. AIMS: In this study, we evaluated the performance of nonfractional monopolar radiofrequency for the improvement of photoaged skin texture and wrinkles. METHODS: In total, 32 6-week-old female hairless mice were randomized into four groups of eight mice each: (a) healthy control, (b) UVB-exposed, (c) UVB + microneedling, and (d) UVB + microneedle RF. After applying each treatment modality, skin surface was globally investigated and histologically evaluated senile skin change. Immunohistochemistry was tested with the primary antibody to collagen type I and III. RESULTS: After UVB exposure, the Ra value was significantly increased, leading to clinical development of wrinkles with xerotic scales. Depth and number of wrinkles showed gradual improvement in RF-treated mice. The mean Ra value of the RF-treated group decreased significantly. The RF-treated group showed decreased epidermal thickness, suppression of dermal inflammatory cell infiltration, and increased density of collagen fibers and amount of elastic fibers. CONCLUSIONS: Microneedle RF treatment alleviates photoaged skin texture and wrinkles in this mouse model. To the best of our knowledge, our results provide the first evidence that a nonfractional monopolar microneedle radiofrequency device may contribute to the treatment of UV-damaged skin.

Mechanism of danshensu-induced inhibition of abnormal epidermal proliferation in psoriasis.

Psoriasis is a chronic, inflammatory skin disease with high incidence and high rates of relapse, for which no satisfactory treatments are currently available. Yes-associated protein (YAP) is highly expressed in psoriasis and may regulate the proliferation and apoptosis of keratinocytes. Danshen is a traditional Chinese medicine, commonly used in the treatment of psoriasis. Danshensu is the most abundant water-soluble component of Danshen, but its therapeutic mechanism is still unclear. In this study, MTT was used to detect the effects of different danshensu concentrations (0.125, 0.25, 0.5 mmol/l) on the proliferation of an M5-based psoriasis cell model. The effects of danshensu on cell cycle and apoptosis were detected by flow cytometry. Cyclins and apoptosis-related proteins were evaluated by Western blot. Danshensu (20, 40, 80 mg/kg/day) was administered intraperitoneally to the imiquimod (IMQ) psoriasis mouse model. After 7 days, the expression of YAP in the lesions was detected by immunohistochemistry and Western blot. We found that danshensu reduced the expression of YAP in the M5 psoriasis cell model, inhibited cell proliferation, induced cell cycle arrest in G0/G1 phase, and promoted cell apoptosis. All these effects were partly reverted by YAP overexpression. The skin lesions of IMQ mice were thinned and the scales reduced after intragastric administration of danshensu, which also resulted in dose-dependent inhibition of YAP expression. We concluded that danshensu prevents abnormal epidermis proliferation in psoriasis possibly by modulating YAP expression. Our work can provide a theoretical basis for the clinical application of Danshen in the treatment of psoriasis.

Hyperalphalipoproteinemic scavenger receptor BI knockout mice exhibit a disrupted epidermal lipid barrier.

Scavenger receptor class B type I (SR-BI) mediates the selective uptake of cholesteryl esters (CE) from high-density lipoproteins (HDL). An impaired SR-BI function leads to hyperalphalipoproteinemia with elevated levels of cholesterol transported in the HDL fraction. Accumulation of cholesterol in apolipoprotein B (apoB)-containing lipoproteins has been shown to alter skin lipid composition and barrier function in mice. To investigate whether these hypercholesterolemic effects on the skin also occur in hyperalphalipoproteinemia, we compared skins of wild-type and SR-BI knockout (SR-BI-/-) mice. SR-BI deficiency did not affect the epidermal cholesterol content and induced only minor changes in the ceramide subclasses. The epidermal free fatty acid (FFA) pool was, however, enriched in short and unsaturated chains. Plasma CE levels strongly correlated with epidermal FFA C18:1 content. The increase in epidermal FFA coincided with downregulation of cholesterol and FFA synthesis genes, suggesting a compensatory response to increased flux of plasma cholesterol and FFAs into the skin. Importantly, the SR-BI-/- epidermal lipid barrier showed increased permeability to ethyl-paraminobenzoic acid, indicating an impairment of the barrier function. In conclusion, increased HDL-cholesterol levels in SR-BI-/- mice can alter the epidermal lipid composition and lipid barrier function similarly as observed in hypercholesterolemia due to elevated levels of apoB-containing lipoproteins.

Evaluation of moisturizing and irritation potential of sacha inchi oil.

OBJECTIVE: The moisturizing and irritation effects of sacha inchi oil were evaluated. STUDY DESIGN: The moisturizing effect on the skin was clinically assessed using a regression study design. Sacha inchi oil or olive oil (benchmark) was applied on the left or right lower leg of the subjects for 14 days followed by application discontinuation for 2 days. The TEWL, skin moisture content and dryness appearance were observed. METHODS: The fatty acid composition and characteristics of cold-pressed sacha inchi seed oil were determined. Skin tissues cultured ex vivo were used to assess primary irritation induced by the oil by examining keratin 1 expression and TNF-α and IL-1α release from the oil-applied tissues. RESULTS: The sacha inchi oil contained 42.3% linolenic acid and 39.5% linoleic acid. This oil's saponification, iodine, acid and peroxide values were 168.58 ± 1.55 mg KOH/g, 203.00 ± 0.04 g I2 /100 g, 1.68 ± 0.03 mg KOH/g, and 1.95 ± 0.26 mEq peroxide/kg, respectively. Compared with nontreated skin tissues, induced secretion of TNF-α and IL-1α and disruption of keratin 1 integrity in the stratum corneum layer were not found in the sacha inchi oil-treated tissues. In a clinical study with 13 volunteers, the improvement in moisture content and skin dryness appearance at the sacha inchi oil-applied site was comparable with that observed at the olive oil-applied site. CONCLUSIONS: The sacha inchi oil was mild to the skin and benefited dry skin.

Two-years of home based functional electrical stimulation recovers epidermis from atrophy and flattening after years of complete Conus-Cauda Syndrome.

To evaluate progression of skin atrophy during 8 years of complete Conus-Cauda Syndrome and its recovery after 2 years of surface Functional Electrical Stimulation a cohort study was organized and implemented.Functional assessments, tissue biopsies, and follow-up were performed at the Wilhelminenspital, Vienna, Austria; skin histology and immunohistochemistry at the University of Padova, Italy on 13 spinal cord injury persons suffering up to 10 years of complete conus/cauda syndrome. Skin biopsies (n. 52) of both legs were analyzed before and after 2 years of home-based Functional Electrical Stimulation delivered by large anatomically shaped surface electrodes placed on the skin of the anterior thigh. Using quantitative histology we analyzed: 1. Epidermis atrophy by thickness and by area; 2. Skin flattening by computing papillae per mm and Interdigitation Index of dermal-epidermal junctions; 3. Presence of Langerhans cells.Linear regression analyses show that epidermal atrophy and flattening worsen with increasing years post- spinal cord injury and that 2 years of skin electrostimulation by large anatomically shaped electrodes reverses skin changes (pre-functional Electrical Stimulation vs post-functional Electrical Stimulation: thickness 39%, P < .0001; area 41%, P < .0001; papillae n/mm 35%, P < 0.0014; Interdigitation index 11%, P < 0.018), producing a significant recovery to almost normal levels of epidermis thickness and of dermal papillae, with minor changes of Langerhans cells, despite 2 additional years of complete Conus-Cauda Syndrome.In complete Conus-Cauda Syndrome patients, the well documented beneficial effects of 2 years of surface h-b Functional Electrical Stimulation on strength, bulk, and muscle fiber size of thigh muscles are extended to skin, suggesting that electrical stimulation by anatomically shaped electrodes fixed to the skin is also clinically relevant to counteract atrophy and flattening of the stimulated skin. Mechanisms, pros and cons are discussed.