Control Skin Research Articles

Identification of Differentially Methylated CpG Sites in Fibroblasts from Keloid Scars.

As a part of an abnormal healing process of dermal injuries and irritation, keloid scars arise on the skin as benign fibroproliferative tumors. Although the etiology of keloid scarring remains unsettled, considerable recent evidence suggested that keloidogenesis may be driven by epigenetic changes, particularly, DNA methylation. Therefore, genome-wide scanning of methylated cytosine-phosphoguanine (CpG) sites in extracted DNA from 12 keloid scar fibroblasts (KF) and 12 control skin fibroblasts (CF) (six normal skin fibroblasts and six normotrophic fibroblasts) was conducted using the Illumina Human Methylation 450K BeadChip in two replicates for each sample. Comparing KF and CF used a Linear Models for Microarray Data (Limma) model revealed 100,000 differentially methylated (DM) CpG sites, 20,695 of which were found to be hypomethylated and 79,305 were hypermethylated. The top DM CpG sites were associated with TNKS2, FAM45B, LOC723972, GAS7, RHBDD2 and CAMKK1. Subsequently, the most functionally enriched genes with the top 100 DM CpG sites were significantly (p ≤ 0.05) associated with SH2 domain binding, regulation of transcription, DNA-templated, nucleus, positive regulation of protein targeting to mitochondrion, nucleoplasm, Swr1 complex, histone exchange, and cellular response to organic substance. In addition, NLK, CAMKK1, LPAR2, CASP1, and NHS showed to be the most common regulators in the signaling network analysis. Taken together, these findings shed light on the methylation status of keloids that could be implicated in the underlying mechanism of keloid scars formation and remission.

Transcriptomes from German shepherd dogs reveal differences in immune activity between atopic dermatitis affected and control skin

Canine atopic dermatitis (CAD) is an inflammatory and pruritic allergic skin disease with both genetic and environmental risk factors described. We performed mRNA sequencing of non-lesional axillary skin biopsies from nine German shepherd dogs. Obtained RNA sequences were mapped to the dog genome (CanFam3.1) and a high-quality skin transcriptome was generated with 23,510 expressed gene transcripts. Differentially expressed genes (DEGs) were defined by comparing three controls to five treated CAD cases. Using a leave-one-out analysis, we identified seven DEGs: five known to encode proteins with functions related to an activated immune system (CD209, CLEC4G, LOC102156842 (lipopolysaccharide-binding protein-like), LOC480601 (regakine-1-like), LOC479668 (haptoglobin-like)), one (OBP) encoding an odorant-binding protein potentially connected to rhinitis, and the last (LOC607095) encoding a novel long non-coding RNA. Furthermore, high mRNA expression of inflammatory genes was found in axillary skin from an untreated mild CAD case compared with healthy skin. In conclusion, we define genes with different expression patterns in CAD case skin helping us understand post-treatment atopic skin. Further studies in larger sample sets are warranted to confirm and to transfer these results into clinical practice.

062 Hidradenitis suppurativa RNA-seq skin transcriptome overlaps with psoriasis vulgaris and reveals a marked upregulation of multiple targetable cytokines

Hidradenitis Suppurativa (HS) is a chronic inflammatory dermatosis of inguinal, axillary, and submammary skin. Using established consensus definitions, unaffected, perilesional and lesional HS skin samples were collected and RNA-sequencing performed. A mixed-effect model was estimated. Hypotheses were tested under the general framework for linear models in the R limma package. P values from t-tests were adjusted for multiple hypotheses using the Benjamini–Hochberg procedure. Statistical analysis revealed a HS transcriptome of approximately 5000 genes (FCH>1.5; fdr<0.05), with HS samples clustering distinctly away from control skin.

Overview on Keloid Disorder: Phenotypic Spectrum, Connective Tissue Pathology, and Treatment Development

Overview on Keloid Disorder: Phenotypic Spectrum, Connective Tissue Pathology, and Treatment Development

Hyperkeratotic hand eczema: Eczema or not?

BackgroundHyperkeratotic hand eczema (HHE) is a typical clinical hand eczema subtype with a largely unknown pathophysiology.ObjectiveTo investigate histopathology, expression of keratins (K), epidermal barrier proteins, and adhesion molecules in HHE.MethodsPalmar skin biopsies (lesional and perilesional) were obtained from seven HHE patients and two healthy controls. Moreover, 135 candidate genes associated with palmoplantar keratoderma were screened for mutations.ResultsImmunofluorescence staining showed a significant reduction of K9 and K14 in lesional skin. Upregulation was found for K5, K6, K16, and K17 in lesional skin compared with perilesional and healthy palmar skin. Further, upregulation of involucrin and alternating loricrin staining, both in an extracellular staining pattern, was found. Filaggrin expression was similar in lesional, perilesional, and control skin. No monogenetic mutations were found.ConclusionCurrently, the phenotype of HHE is included in the hand eczema classification system; however, it can be argued whether this is justified. The evident expression of filaggrin and involucrin in lesional skin does not support a pathogenesis of atopic eczema. The upregulation of K6, K16, and K17 and reduction of K9 and K14 might contribute to the underlying pathogenesis. Unfortunately, comparison with hand eczema studies is not possible yet, because similar protein expression studies are lacking.

Vanin-1 Gene Expression in Acne Vulgaris and its Correlation with Disease Severity

Background: Acne vulgaris is the most prevalent chronic disease worldwide, occurs during adolescence. The pathogenesis is multifactorial with different grades of severity and the human vanin gene family especially vanin-1 might play a role in pathogenesis of acne. Aim: explore the role of Vanin-1 in acne vulgaris and its correlation with disease severity, duration, weight and residency. Patient and method: 42 acne patients and 42 age and sex matched healthy controls were enrolled. Skin biopsies were taken from the patient and normal skin of controls. Vanin-1 gene expression was estimated by real time PCR. Results: Expression of Vanin-1 gene in acne patients was significantly higher than healthy controls (p-value<0.001), also, there are positive correlation between VNN1 gene expression and patients weight and acne duration (P<0.001), also VNN1 gene expression is significantly higher among urban as compared with rural patients. Conclusion: VNN-1 gene expression is significantly higher in acne patients than healthy controls indicating thatVanin-1 gene involved in pathogenesis of acne vulgaris. In dermatological diseases; Vanin-1 might be a new promising target for therapeutic intervention in acne vulgaris.

Immunogenicity and protective efficacy of Yersinia ruckeri lipopolysaccharide (LPS), encapsulated by alginate-chitosan micro/nanoparticles in rainbow trout (Oncorhyncus mykiss)

Considering the many advantages of oral vaccines in aquaculture, several studies have been conducted in this area recently. In this study, immunization and protective power of the oral vaccine of Yersinia ruckeri encapsulated with Alginate-Chitosan micro/nanoparticles were evaluated in rainbow trout. For this purpose, 720 juvenile rainbow trout (9 ± 1.8 g) were divided into 8 groups in three replications (30 fish each) as follows: Groups A, B and C, were immunized with Yersinia ruckeri lipopolysaccharide (LPS), LPS+Formalin Killed Cells (FKC) and FKC alone, groups D, E, and F were immunized with encapsulated LPS, LPS+FKC and FKC, respectively. The G and H groups considered as encapsulated and non-encapsulated control, respectively. Micro/nanoencapsulation with alginate-chitosan was performed by internal emulsification method and vaccination were conductrd in the first and third weeks via oral route. Sampling was performed on days 0, 30, and 60 of experiment. Anti Y. ruckeri antibody titer in serum, intestine and skin mucus were measured via ELISA method. Non-specific immune response including: serum lysozyme, complement, bactericidal and respiratory burst activity, serum protein and globulin level, as well as white blood cell count were compared among the groups. The expression of IgT gene in the intestine and TCR gene in the anterior kidney were also investigated. At the end of the study, the fish were challenged with Y. ruckeri through immerssion and intraperitoneal routs and the relative survival rate was evaluated. Result showed that the antibody level in serum, skin and intestine was significantly higher in group E and F than control groups (P < 0.05), meanwhile serum, skin and intestine antibody level in all vaccinated groups were significantly (P < 0.01) higher in day 30 and 60 compare to zero day. Non-specific immunity factors including: serum lysozyme, complement, and respiratory burst activity as well as WBC, protein and Globulin level were significantly higher in E and F groups not only in day 30 but also in day 60 of experiment (P < 0.05). Cumulative mortality following injection and bath challenge were significantly (P = 0.004) lower (35%–45%) in groups E and F compare to control group (80%). The IgT and TCR gene expression in groups D, E and F were significantly higher (P < 0.05) than control group. Highest upregulation of IgT and TCR gene expression in vaccinated groups were seen at day 30 and 60 respectively which were significantly (P < 0.001) higher than day zero. Generally, it can be concluded that nano/micronanoencapsulation of Y. ruckeri FKC+LPS with chitosan-alginate, not only increases protective efficacy of oral vaccine, but improves specific and non-specific immune responses in rainbow trout.

Skin remodeling and wound healing in the Gottingen minipig following exposure to sulfur mustard

Sulfur mustard (SM), a dermal vesicant that has been used in chemical warfare, causes inflammation, edema and epidermal erosions depending on the dose and time following exposure. Herein, a minipig model was used to characterize wound healing following dermal exposure to SM. Saturated SM vapor caps were placed on the dorsal flanks of 3-month-old male Gottingen minipigs for 30 min. After 48 h the control and SM wounded sites were debrided daily for 7 days with wet to wet saline gauze soaks. Animals were then euthanized, and full thickness skin biopsies prepared for histology and immunohistochemistry. Control skin contained a well differentiated epidermis with a prominent stratum corneum. A well-developed eschar covered the skin of SM treated animals, however, the epidermis beneath the eschar displayed significant wound healing with a hyperplastic epidermis. Stratum corneum shedding and a multilayered basal epithelium consisting of cuboidal and columnar cells were also evident in the neoepidermis. Nuclear expression of proliferating cell nuclear antigen (PCNA) was contiguous in cells along the basal epidermal layer of control and SM exposed skin; SM caused a significant increase in PCNA expression in basal and suprabasal cells. SM exposure was also associated with marked changes in expression of markers of wound healing including increases in keratin 10, keratin 17 and loricrin and decreases in E-cadherin. Trichrome staining of control skin showed a well-developed collagen network with no delineation between the papillary and reticular dermis. Conversely, a major delineation was observed in SM-exposed skin including a web-like papillary dermis composed of filamentous extracellular matrix, and compact collagen fibrils in the lower reticular dermis. Although the dermis below the wound site was disrupted, there was substantive epidermal regeneration following SM-induced injury. Further studies analyzing the wound healing process in minipig skin will be important to provide a model to evaluate potential vesicant countermeasures.

Methylated DNA marker panel for metastatic melanoma: Discovery and tissue validation.

e22024 Background: Disease surveillance in high risk melanoma patients using PET/CT is recommended every 6 months, an algorithm that is extremely expensive and often difficult to access. Biomarkers capable of detecting recurrence and low volume metastasis have application in tools to improve the cost effectiveness of surveillance. Towards this long term goal, our aim was to discover melanoma-specific methylated DNA markers (MDMs). Methods: Candidate MDMs were identified by reduced representation bisulfite sequencing of selected age- and sex-balanced snap frozen metastatic melanoma, benign control skin and white blood cells. Sequences were filtered for highest methylation difference, lowest control methylation background ( &lt; 1%), and highest discrimination by variance inflated logistic regression. Using formalin-fixed tissues, the top 32 MDMs were further evaluated in metastatic melanoma from 35 patients, primary melanoma from 26 patients, and 73 control samples (47 benign precursor lesions or normal skin, and 26 healthy buffy coat samples to assess for background DNA in circulation). Candidate markers were blindly assayed by quantitative methylation specific PCR. After normalization by within sample ACTB level, random forest modeling with cross-validation identified marker combinations with greatest predictive accuracy. Results: On receiver operator characteristics analyses of individual marker candidates, areas under the curve (AUCs) ranged from 0.43 to 0.97. Median AUC was 0.835. At 100% specificity, a cross-validated panel of five MDMs (see Table), yielded a sensitivity of 33/35 cases (94.3%; 95% CI, 86.6-100%) for metastatic melanoma and 22/26 cases (84.6%; 95% CI, 70.7-98.5%) for primary melanoma. Furthermore, none of the 5 markers were detected in normal buffy coat samples. Conclusions: A panel of five novel MDMs assayed on tissue and undetectable in normal buffy coat achieves very high discrimination between melanoma and benign control tissues. This panel can be assessed in blood or other bodily fluids for application in melanoma surveillance. [Table: see text]

Rainbow trout Oncorhynchus mykiss skin responses to salmon louse Lepeophtheirus salmonis: From copepodid to adult stage

The marine crustacean Lepeophtheirus salmonis (salmon louse) is a common ectoparasite of wild and farmed salmonids. The parasite has a complex ontogeny comprising eight instars. The planktonic copepodid stage settles on host skin and pass through five instars to reach the adult stage. The present study comprises an experimental infestation of Oncorhynchus mykiss (rainbow trout) with salmon lice and describes histopathology and host immune responses in skin beneath the louse at multiple time points encompassing all louse developmental stages. Each fish was exposed to 80 infective copepodids, a mean no. of 32 parasites reached the preadult I stage whereas a mean no. of 11 parasites reached the adult stage. A progression in the severity of cutaneous lesions was observed, and levels of immune gene transcripts at the attachment site revealed a dynamic response, initially related to innate immunity. Later, immune cells accumulated in the dermis concomitant with a moderate decrease in levels of transcripts characteristic of both innate and adaptive immune responses. The present study also demonstrates that the cutaneous immune response was mainly induced at lice affected sites, while non-affected skin resembled the skin of untreated control. This indicates that the skin cannot be regarded as a uniform organ and requires careful sampling at all salmon louse stages.

Cutaneous Breast Cancer Metastases Successfully Treated Using an Oxygen Flow Assisted Topical Administration of Methotrexate (OFAMTX).

IntroductionCutaneous metastases of breast cancer remain a therapeutic challenge. Oxygen flow-assisted topical administration of methotrexate 5% (OFAMTX, 5% methotrexate in a carrier solution) has recently been proven to be an efficacious alternative treatment for extramammary Paget’s disease, which is considered to be an in situ mammary adenocarcinoma of the epidermis.Case ReportA 51-year-old patient with triple negative breast cancer presenting with biopsy-proven skin metastases on the chest agreed to a treatment with OFAMTX5%. The treatment duration was 2 weeks and consisted of twice-weekly sessions with OFAMTX5% applied to an area of skin of approximately 40 cm2. Skin biopsies were performed before and 2 months after procedure. The tolerance to the treatment was excellent, and no pain sensations were experienced. Two months post-procedure the treated area presented a post-inflammatory hyperpigmentation. No residual metastatic lesions were detectable on the control skin biopsy. Six months post-procedure the patient is still in clinical remission.DiscussionOFAMTX5% represents an alternative skin-directed, painless, patient-friendly and efficacious adjuvant treatment for superficial metastatic lesions of breast cancer. Larger series are required to evaluate the potential of OFAMTX5% for the treatment of superficial metastatic lesions of breast cancer.

Aberrant ETS-1 signalling impedes the expression of cell adhesion molecules and matrix metalloproteinases in non-segmental vitiligo.

Cell adhesion is a complex process that involves multiple molecules on the cell surface (ie cell adhesion molecules [CAMs]), surrounding cells and extracellular matrix (ECM). Repigmentation in vitiligo is dependent on the ECM remodelling and cellular migration, primarily attributed to the transcriptional activation of matrix metalloproteinases (MMPs). In this study, we aimed to demonstrate the role of ETS-1 signalling in the regulation of MMPs and CAMs. Therefore, we studied the expression of ETS-1, MMPs (MMP-2, MMP-9) and CAMs including E-cadherin, ITGA-1 and ICAM-1 in vitiligo (both active and stable) ex vivo. Further, we compared melanocyte morphology and their adhesion towards collagen IV and laminin between control and vitiligo groups in vitro. Also, we silenced ETS-1 in melanocytes cultured from control skin and observed post-silencing effect on above-mentioned MMPs and CAMs. We perceived absent ETS-1 and significantly reduced CAMs and MMPs in vitiligo compared with normal skin. Scanning electron microscopy (SEM) revealed a translucent material surrounding individual melanocytes in stable vitiligo and controls, whereas active vitiligo melanocytes demonstrated loss of this extracellular substance. Adhesion assays revealed significantly decreased binding of cultured melanocytes to collagen IV and laminin V plates in both stable and active vitiligo. Importantly, ETS-1 silencing resulted in significantly reduced expression of CAMs and MMPs. In conclusion, absent ETS-1 expression in both stable and active non-segmental vitiligo seems to impede the expression of CAMs, apart from MMPs, probably leading to progressive depigmentation in active disease and absence of spontaneous repigmentation in stable disease.

Successful Regulatory T Cell-Based Therapy Relies on Inhibition of T Cell Effector Function and Enrichment of FOXP3+ Cells in a Humanized Mouse Model of Skin Inflammation.

Background Recent clinical trials using regulatory T cells (Treg) support the therapeutic potential of Treg-based therapy in transplantation and autoinflammatory diseases. Despite these clinical successes, the effect of Treg on inflamed tissues, as well as their impact on immune effector function in vivo, is poorly understood. Therefore, we here evaluated the effect of human Treg injection on cutaneous inflammatory processes in vivo using a humanized mouse model of human skin inflammation (huPBL-SCID-huSkin). Methods SCID beige mice were transplanted with human skin followed by intraperitoneal (IP) injection of 20‐40 × 106 allogeneic human PBMCs. This typically results in human skin inflammation as indicated by epidermal thickening (hyperkeratosis) and changes in dermal inflammatory markers such as the antimicrobial peptide hBD2 and epidermal barrier cytokeratins K10 and K16, as well as T cell infiltration in the dermis. Ex vivo-expanded human Treg were infused intraperitoneally. Human cutaneous inflammation and systemic immune responses were analysed by immunohistochemistry and flow cytometry. Results We confirmed that human Treg injection inhibits skin inflammation and the influx of effector T cells. As a novel finding, we demonstrate that human Treg injection led to a reduction of IL-17-secreting cells while promoting a relative increase in immunosuppressive FOXP3+ Treg in the human skin, indicating active immune regulation in controlling the local proinflammatory response. Consistent with the local control (skin), systemically (splenocytes), we observed that Treg injection led to lower frequencies of IFNγ and IL-17A-expressing human T cells, while a trend towards enrichment of FOXP3+ Treg was observed. Conclusion Taken together, we demonstrate that inhibition of skin inflammation by Treg infusion, next to a reduction of infiltrating effector T cells, is mediated by restoring both the local and systemic balance between cytokine-producing effector T cells and immunoregulatory T cells. This work furthers our understanding of Treg-based immunotherapy.

Ethanol-Based Disinfectants Containing Urea May Reduce Soap Sensitivity.

The use of disinfectants is crucial to preventing the spread of nosocomial infections in health care workers. As many as 25 applications of hand disinfectants is a realistic default value during a working day. However, alcohol-based hand disinfectants may weaken skin barrier function and induce dryness and eczema, which decrease their acceptance. To evaluate the effect of ethanol-containing disinfectants with 5% urea on skin barrier function and on sensitivity to an irritant soap (sodium lauryl sulfate [SLS]). Twenty healthy volunteers treated one of their forearms twice daily for 17 days with an ethanol-containing gel with 5% urea. Two types of gels with urea were tested. Treatment was randomized to left or right forearm, and the contralateral forearm served as untreated control. Transepidermal water loss, skin capacitance (dryness), and sensitivity to SLS were evaluated. Twice-daily application of the urea-containing ethanol gels lowered transepidermal water loss, prevented dryness, and reduced sensitivity to SLS compared with the untreated control skin. Improved barrier function using this ethanol gel with urea may have relevance in daily disinfectant procedures.

Evaluation of the optical and biomechanical properties of bioengineered human skin generated with fibrin-agarose biomaterials.

.Significance: Recent generation of bioengineered human skin allowed the efficient treatment of patients with severe skin defects. However, the optical and biomechanical properties of these models are not known.Aim: Three models of bioengineered human skin based on fibrin-agarose biomaterials (acellular, dermal skin substitutes, and complete dermoepidermal skin substitutes) were generated and analyzed.Approach: Optical and biomechanical properties of these artificial human skin substitutes were investigated using the inverse adding-doubling method and tensile tests, respectively.Results: The analysis of the optical properties revealed that the model that most resembled the optical behavior of the native human skin in terms of absorption and scattering properties was the dermoepidermal human skin substitutes after 7 to 14 days in culture. The time-course evaluation of the biomechanical parameters showed that the dermoepidermal substitutes displayed significant higher values than acellular and dermal skin substitutes for all parameters analyzed and did not differ from the control skin for traction deformation, stress, and strain at fracture break.Conclusions: We demonstrate the crucial role of the cells from a physical point of view, confirming that a bioengineered dermoepidermal human skin substitute based on fibrin-agarose biomaterials is able to fulfill the minimal requirements for skin transplants for future clinical use at early stages of in vitro development.

Establishment of a Novel Mouse Model for Soft Tissue Expansion

BackgroundDespite its increasing use, not much is known about tissue expansion, and its complication rates are significantly high. Thus, there is an urgent need to establish a stable animal model to overcome the limitations and complications of tissue expansion. Although the mouse model has shown several advantages in the in-depth studies, an appropriate mouse expansion model has rarely been reported, likely because of its loose skin. Materials and methodsA micro expander was designed and implanted under the scalp of a mouse (expanded group); sterilized saline was regularly injected into the expander. In sham-operated mice (control group), a silicone sheet was implanted under the scalp. Skin samples were collected 5 wk after surgery. Histologic changes including epidermal and dermal thickness and collagen fiber arrangement were analyzed. In addition, vascular density and cell proliferation ratio were determined. An ultrastructural analysis was also performed. ResultsWith the application of the expansion device, the skin became tight and showed area enlargement. The epidermal thickness of the expanded skin increased significantly (P < 0.01), whereas the thickness of the dermis decreased significantly (P < 0.05) as compared with the control skin. Masson staining demonstrated that collagen bundles were arranged more compactly in the expanded skin (P < 0.05) than in the controls. Furthermore, more proliferating cells (P < 0.05) and blood vessels (P < 0.01) were observed. Transmission electron microscopy showed that the fibers of expanded skin were stretched and broken into bundles of various diameters, with abundant active fibroblasts. ConclusionsA reliable mouse model of scalp skin expansion was successfully established, which may be a promising tool for in-depth studies on skin soft tissue expansion.

Cytoplasmic Increase in Hsp70 Protein: A Potential New Biomarker of Early Infiltration of Cutaneous Squamous Cell Carcinoma Arising from Actinic Keratosis.

Background: Cutaneous squamous skin cell carcinoma (SCC) is the second most frequent type of non-melanoma skin cancer and is the second leading cause of death by skin cancer in Caucasian populations. However, at present it is difficult to predict patients with poor SCC prognosis. Objective: To identify proteins with expression levels that could predict SCC infiltration in SCC arising from actinic keratosis (SCC-AK). Methods: A total of 20 biopsies from 20 different patients were studied; 10 were SCC-AK samples and 10 were taken from normal skin. Early infiltrated SCC-AK samples were selected based on histological examination, and to determine the expression of proteins, fresh skin samples were processed by two-dimensional electrophoresis. Results: The expression levels of three proteins, namely alpha hemoglobin and heat shock proteins 27 and 70 (Hsp27 and Hsp70, respectively) were significantly increased in SCC-AK samples with respect to normal control skin. However, only the expression level of Hsp70 protein positively correlated with the level of SCC-AK dermis infiltration. Immunohistological examination suggested that increased expression of Hsp70 proteins seemed to mainly occur in the cytoplasm of keratinocytes. The increased cytoplasmic Hsp70 expression in SCC-AK was confirmed by Western blot experiments. Conclusion: Cytoplasmic expression of Hsp70 could be a potential biomarker of early infiltration of SCC arising from AK.

De-Oiled Karanja Cake as Potential Bio-Additive for Low Salt Raw Skin Preservation

The most commonly practiced preservation processes for raw hide/skin is by application of common salt (NaCl) due to its wide availability, cost effectiveness and bacteriostatic activity. During the soaking process, the salt present in the skin dissolves in water, thereby generating high total dissolved solids (TDS) levels causing pollution to the environment. Hence, an eco–friendly material without salt or with lower quantities of salt is needed for the preservation of the skin. In this present study Karanja de-oiled cake (Millettia/Pongamia pinnata) extract was studied for its antibacterial activity, minimal inhibitory concentration and minimum bactericidal concentration for preservation. The reverse phase high performance liquid chromatography (RP-HPLC) analysis shows the presence of karanjin (0.2%) and pongamol (0.02%) and these compounds may be responsible for the antibacterial activity against skin deteriorating bacteria. The preservation trials with karanja de-oiled cake 15% along with less salt 15% showed no hair slip, no putrefaction, reduced bacterial load to approximately 35%, compared to control skins at 25º-35ºC for 21 days. The preserved skins on rehydration showed that the soak liquor of experimental skins had a considerable reduction in TDS (about 67%) compared with conventional soak liquor. On processing these skins into leather, the experimental skins were found to possess comparable strength properties (tensile, tear strength) and organoleptic properties as conventional salt-based preserved skins. This study concludes that conventional salt-based preservation of skins can be replaced by an eco-friendly preservation method using karanja de-oiled cake along with less salt.

Smad7 in psoriasis vulgaris patients: A clinical and immunohistochemical study.

Psoriasis is an inflammatory disease that is mostly immune-derived. It causes proliferation of skin cells, forming plaques. Psoriasis etiology is unknown. It might be multifactorial. This work aimed to study Smad7 expression in psoriasis vulgaris patients in comparison with normal skin. Thirty patients with psoriasis vulgaris in comparison with 20 age- and sex-matched seemingly healthy individuals were selected. We used psoriasis area and severity index (PASI) to evaluate psoriasis severity. Skin biopsies were prepared from skin lesions (30), perilesions (30) and control (20) groups for histopathological and immunostaining evaluation of Smad7. Smad7 was progressively upregulated in proliferating keratinocytes from controls (58.18±30.93) to perilesional (106±38.93) and lesional (156.33±62.01) skin (P<.001). Also, dermal inflammatory cells showed upregulation of Smad7 expression from control skin (40±28.28) to skin lesions (137.33±73.86) (P<.010). Smad7 expression showed a positive significant correlation with psoriasis severity (r=.452; P<.012). Smad7 may be involved in increased keratinocyte proliferation as well as skin inflammation in psoriasis vulgaris patients.

Topical application of a commercially available formulation of vitamin C stabilized by vitamin E and ferulic acid reduces tissue viability and protein synthesis in ex vivo human normal skin.

Aqueous formulations of vitamin C stabilized by vitamin E and ferulic acid at low pH effectively protect skin against reactive oxygen species-induced damage. However, the effects of these formulations on human skin have not clearly been described. The aim of this study was to investigate whether topical application of two commercially available formulations of vitamin C alter human skin using an ex vivo model. Human skin explants were topically treated on alternate days with commercially available formulation 1 (15% vitamin C) at 100% (without dilution), 50%, or 10% diluted in saline or formulation 2 (20% vitamin C) at 100% (without dilution), 50%, or 10% diluted in saline. Only saline was applied to control skin explants. Topical formulation 1 at 100%, 50%, or 10%, but not formulation 2 at 100%, 50%, or 10%, reduced the viability of ex vivo human skin compared to the control after 7, 10, and 13days. In addition, compared to the control, ex vivo human skin treated with formulation 1 at 50%, but not formulation 2 at 50%, also decreased mRNA levels of actin and ribosomal protein L10 and gene expression of extracellular matrix components after 10days. Furthermore, after 10days, topical application of formulation 1 at 50%, but not formulation 2 at 50%, decreased the protein expression of proliferating cellular nuclear antigen, lysyl oxidase, β-actin, and glyceraldehyde-3-phosphate dehydrogenase compared to the control. Topical formulation 1, but not formulation 2, may reduce the viability of and protein synthesis in ex vivo human skin. Those effects might be due to action of vehicle of formulation 1 on ex vivo human skin.