Skin Histopathology Research Articles

Primary Systemic Amyloidosis Presenting as Skin Vegetations: A Case Report

Introduction: Primary systemic amyloidosis is characterized by clonal plasma cell disorder, and its signs and symptoms are various and complex, damage to the skin and mucous membrane is often more likely to attract attention.Here we reported a case of a 61-year-old male patient who presented with topical mucocutaneous lesion, as well unusual skin vegetations. Case presentation: A 61-year-old man was hospitalized due to repeated burning sensation on his back, multiple ecchymosis, and skin vegetations. Through a series of examinations (mainly including skin histopathology, bone marrow cytology, bone marrow flow cytometry, immunofixation electrophoresis), Primary systemic amyloidosis was diagnosed, but multiple myeloma could not be diagnosed. Subsequently, he received chemotherapy. In the half-year follow-up, there was no significant change in his symptoms and signs. Discussion: In this case, in addition to the typical skin damage of primary amyloidosis, the multiple skin vegetations in the buttocks, abdomen, and arms are particularly noteworthy. According to the histopathology and Immunohistochemistry of the skin vegetation, we infer that the formation mechanism of these skin vegetation is lymphatic obstruction caused by amyloid, which leads to lymphatic dilatation, lymph leakage, and dermal edema. Conclusion: Primary systemic amyloidosis is a rare disease, which is often difficult to diagnose. We should be alert to those atypical skin features so as not to delay diagnosis.

Paracoccidioidomycosis in an Elderly Simulating Cholangiocarcinoma

Paracoccidioidomycosis, the most prevalent deep mycosis in Latin America, is caused by dimorphic species of the genus Paracoccidioides, affects predominantly male rural workers between 30-50 years of age and is an important cause of morbidity and mortality. It can present in two clinical forms: acute/subacute or chronic. In rare cases paracoccidioidomycosis may simulate neoplasia and must be considered as a differential diagnosis of intra-abdominal tumors in endemic areas. We report an exuberant case of subacute paracoccidioidomycosis in an elderly lady, although it is more frequent in the juvenile form. Multiple facial skin lesions were associated with a wasting syndrome and extensive adenopathy including in the hepatic area, causing bile duct dilatation simulating a cholangiocarcinoma. Skin histopathology was diagnostic and antifungal treatment allowed complete resolution of cutaneous and systemic lesions, thus highlighting the merit of the dermatologist, who was fundamental for the conclusive diagnosis and institution of specific therapy, resulting in a favorable outcome.

A frameshift insertion in FA2H causes a recessively inherited form of ichthyosis congenita in Chianina cattle

The aim of this study was to characterize the phenotype and to identify the genetic etiology of a syndromic form of ichthyosis congenita (IC) observed in Italian Chianina cattle and to estimate the prevalence of the deleterious allele in the population. Sporadic occurrence of different forms of ichthyosis including IC have been previously reported in cattle. However, so far, no causative genetic variant has been found for bovine IC. Nine affected cattle presenting congenital xerosis, hyperkeratosis and scaling of the skin as well as urolithiasis and cystitis associated with retarded growth were examined. Skin histopathology revealed a severe, diffuse orthokeratotic hyperkeratosis with mild to moderate epidermal hyperplasia. The pedigree records indicated a monogenic recessive trait. Homozygosity mapping and whole-genome sequencing allowed the identification of a homozygous frameshift 1 bp insertion in the FA2H gene (c.9dupC; p.Ala4ArgfsTer142) located in a 1.92 Mb shared identical-by-descent region on chromosome 18 present in all cases, while the parents were heterozygous as expected for obligate carriers. These findings enable the selection against this sub-lethal allele showing an estimated frequency of ~ 7.5% in Chianina top sires. A sporadic incidence of mild clinical signs in the skin of heterozygous carriers was observed. So far, pathogenic variants affecting the encoded fatty acid 2-hydroxylase catalyzing the synthesis of 2-hydroxysphingolipids have been associated with myelin disorders. In conclusion, this study represents the first report of an FA2H-related autosomal recessive inherited skin disorder in a mammalian species and adds FA2H to the list of candidate genes for ichthyosis in humans and animals. Furthermore, this study provides a DNA-based diagnostic test that enables selection against the identified pathogenic variant in the Chianina cattle population. However, functional studies are needed to better understand the expression of FA2H in IC-affected Chianina cattle.

Effect of Aeromonas sobria infection on gills and skin histopathology of the Nile tilapia reared under biofloc and clear water systems

Effect of Aeromonas sobria infection on gills and skin histopathology of the Nile tilapia reared under biofloc and clear water systems

Mechanism of improving skin barrier function in a mouse model of atopic dermatitis using Mahuang Lianqiao Chixiaodou decoction and its disassembled formula

To reveal the mechanism of Mahuang Lianqiao Chixiaodou decoction and its disassembled formula for improving the skin barrier function in a mouse model of atopic dermatitis (AD). Sixty specific-pathogen free male BALB/c mice were randomly divided into the control group, model group, whole formula group (WF), exterior-releasing formula group (ERF), interior-clearing formula group (ICF), and positive control group (PC). A mouse model of AD was established using the semi-antigen 2,4-dinitrofluorobenzene induction method. The lesion scores, transepidermal water loss and pH, and skin histopathology of mice in each group were observed. The expressions of filaggrin, loricrin, and involucrin were detected by the streptavidin peroxidase immunohistochemical method and western blotting, and their mRNA expressions were detected by quantitative polymerase chain reaction. Mice in the WF, ERF, ICF, and PC groups showed reduced skin lesion performance, improved histopathology, decreased skin lesion score, transepidermal water loss and pH, and upregulated expressions of proteins including filaggrin, loricrin, and involucrin, and their mRNAs. The most obvious regulatory effect was observed in the WF group, followed by the ICF, ERF, and PC groups, accordingly. Mahuang Lianqiao Chixiaodou decoction and its disassembled formula can improve the skin barrier function in a mouse model of AD by upregulating filaggrin, loricrin, and involucrin, and their mRNA expressions, and the most optimal effect was noted in the WF group, followed by the ICF and ERF groups, which suggests that the effect of clearing heat and resolving dampness in improving the skin barrier function of AD is more obvious and is one of the key treatments for AD.

Dermoscopic Patterns in Relation to the Clinicopathologic Manifestations of Leprosy

Objectives. Leprosy is a chronic granulomatous infection caused by the obligate intracellular organism Mycobacterium leprae. Current diagnostic tests for confirmation and treatment monitoring such as slit skin smear and biopsy are invasive and require time for processing, reading, and interpretation. Dermoscopy is a technique that allows the visualization of structures not readily seen by the naked eye. It can be performed at the point of care, providing a non-invasive link between clinical and histopathologic examination. This study aimed to determine the dermoscopic findings and associated clinicopathologic findings of the different forms of leprosy.
 Methods. A cross-sectional study was conducted. All new and follow-up patients aged 19 years old and above clinically diagnosed with leprosy were invited to participate in the study during the three-month investigation period. Clinical and dermoscopic photographs of representative skin lesions were taken, and a review of slit skin smear and histopathology results was done. Data analysis was performed using Stata SE version 13. The association between dermoscopic findings and the following parameters: anatomic location, Ridley-Jopling classification, WHO classification, treatment duration, and average bacteriologic index were analyzed using Fisher’s exact test. The level of significance was set at 5%.
 Results. A total of 57 lesions were included. Linear vessels (p=0.031), structureless areas (p=0.008), and globules (p=0.002) were found to be significantly associated with the anatomic location. Decreased hair was found to be significantly associated with treatment duration (p=0.038). No significant associations were found between dermoscopic findings and Ridley-Jopling classification, WHO classification, and ABI. Eight biopsies taken at the time of dermoscopy were reviewed, with all sites showing structureless or globular areas corresponding to the presence of granulomas on histopathology (100%). No other notable associations were observed.
 Conclusion. Dermoscopy is a potentially useful tool to aid in the diagnosis and treatment monitoring of leprosy. Limitations of this study include the small sample size, the preponderance of subjects in the lepromatous pole, and assessments by a single trained dermoscopist. A longer study duration including a larger number of newly diagnosed leprosy patients is recommended.

Formulation Development, Statistical Optimization, In Vitro and In Vivo Evaluation of Etoricoxib-Loaded Eucalyptus Oil-Based Nanoemulgel for Topical Delivery

Pain is a common distress in chronic inflammatory diseases, and etoricoxib (ETB) is frequently used in its management. It possesses fewer adverse effects when compared with other non-steroidal anti-inflammatory drugs (NSAIDs). In the present study, ETB-loaded nanoemulsion (ETB-NE) was formulated and optimized. Eucalyptus oil, Tween 20, and PEG 200 were chosen as the oil, surfactant, and co-surfactant, respectively. The formulation was optimized using the Box–Behnken design. The optimized ETB-NE contained oil, Smix, and water in concentrations of 11.5, 38, and 50% respectively. It had droplet size, polydispersity index, and zeta potential values of 179.6 ± 4.21 nm, 0.373 ± 0.02, and −10.9 ± 1.01 mV, respectively. The optimized ETB-NE sample passed the thermodynamic stability and dispersibility tests. Transmission electron microscopy confirmed the spherical morphology of the NE droplets. The ETB-NE showed a biphasic drug release pattern and released 85.3 ± 1.8% of ETB at 12 h. The ETB-NE was formulated into nanoemulsion gel (NEG) by using 1% carbopol 934. ETB-NEG was characterized for pH, viscosity, drug content, and percentage entrapment efficiency. During in vitro permeation studies, the apparent permeability coefficient value was 0.072 cm−2 h−1 for ETB-NEG, while it was only 0.047 cm−2 h−1 for the ETB gel. The skin histopathology study results confirmed that the ETB-NEG formulation was non-irritant and safe for topical use. The maximum possible analgesia observed for ETB-NEG was significantly high (p < 0.05) with a value of 47.09% after 60 min. Similarly, a formalin-induced acute inflammatory pain study in rats also demonstrated higher analgesia for the ETB-NEG, with % inhibition values of 37.37 ± 5.9 and 51.95 ± 4.4 in the acute and late phases, respectively. Further, ETB-NEG showed 78.4 ± 3.5% inhibition at 8 h in the in vivo anti-inflammatory testing by rat paw edema method. The ETB-NEG was found to enhance the in vivo analgesic and anti-inflammatory effects of ETB. The study results could stimulate further studies in this area for establishing a clinically successful NEG formulation of ETB.

27586 Beyond digital pathology: A portable microscope for painless, real-time examination of skin histopathology without biopsy

The Covid-19 pandemic has spurred growing interest in digital pathology solutions. Despite recent advances, these technologies remain wholly dependent on glass slides and by extension, biopsies. This dependence means current technologies can neither curb the number of biopsies nor enable earlier detection for the over 5 million skin cancers treated in the United States every year. We report the creation of a truly slide-free microscope for free hand cellular imaging of living skin without cuts or stains.

Evaluation of High-Efficiency Image Coding algorithm for dermatology images in teledermatology.

Currently, teledermatology assumes a progressively greater role in the modern healthcare system, especially in consultation, diagnosis, or examining lesions and skin cancers. One of the major challenges facing teledermatology systems is determining the optimal image compression method to efficiently reduce the space needed for electronic storage and data transmission. To the objective and subjective assessment of HEIC compression method on dermatological color images and benchmarking the performance of High-Efficiency Image Coding (HEIC) with different algorithms to a feasibility study of the method for teledermatology. Twenty-five clinical and five skin histopathology images were taken in department of dermatology, Imam Reza Hospital, Mashhad, Iran. For each image, a set of 24 compressed images with different compression rates, which is composed of eight JPEG, eight JPEG2000, and eight HEIC images, has been prepared. Compressed and original images were shown simultaneously to three dermatologists and one dermatopathologist with different experiences. Each dermatologist scored quality and suitability of compressed images for diagnostic, as well as educational/scientific purposes. An objective evaluation was performed by calculating the mean "distance" of pixel colors and peak signal-to-noise ratio (PSNR). All compression rates for HEIC were objectively better than JPEG and JPEG2000, particularly at PSNR. Moreover, mean "color distance" per pixel for compressed images using HEIC was lower than others. The subjective image quality assessment also confirms the results of objective evaluation. In both educational and clinical diagnostic applications, HEIC compressed images have the highest score. In consideration of objective and subjective evaluation, the HEIC algorithm represents an optimal performance in dermatology images compression compared with JPEG and JPEG2000.

Evidence concerning the accusation that melanoma is overdiagnosed

Melanoma is one of the most commonly diagnosed malignancies in the United States and is responsible for the majority of deaths from skin cancer. Since the 1970s, the incidence of melanoma has risen appreciably while melanoma-specific mortality has remained stable. This has raised a debate about potential overdiagnosis of melanoma. Herein, we review temporal trends in melanoma incidence and mortality and explore factors that may contribute to observed trends, including an aging population in the United States, ultraviolet exposure, increased numbers of biopsies by dermatologists and physician extenders, skin cancer screenings, histopathology criteria, and historic underdiagnosis. Additionally, we discuss melanoma overdiagnosis and the extent to which it may contribute to current trends. The literature was reviewed. Several factors may contribute to an increased incidence of melanoma, including an aging population, ultraviolet exposure, increased skin biopsies, skin cancer screenings, histopathologic criteria, historic underdiagnosis, and current overdiagnosis. Further studies are required to determine exactly which tumors are being overdiagnosed, and how to improve patient outcomes with adjustment to physician's practice. The rise in the incidence of melanoma observed since the 1970s is likely multifactorial.

Safety and Gadolinium Distribution of the New High-Relaxivity Gadolinium Chelate Gadopiclenol in a Rat Model of Severe Renal Failure.

The aim of this study was to investigate the toxicological profile of gadopiclenol, a new high-relaxivity macrocyclic gadolinium-based contrast agent (GBCA), in renally impaired rats, in comparison with 2 other macrocyclic GBCAs, gadoterate meglumine and gadobutrol, and 1 linear and nonionic GBCA, gadodiamide. Renal failure was induced by adding 0.75% wt/wt adenine to the diet for 3 weeks. During the second week of adenine-enriched diet, the animals (n = 8/group × 5 groups) received 5 consecutive intravenous injections of GBCA at 2.5 mmol/kg per injection, resulting in a cumulative dose of 12.5 mmol/kg or saline followed by a 3-week treatment-free period after the last injection. The total (elemental) gadolinium (Gd) concentration in different tissues (brain, cerebellum, femoral epiphysis, liver, skin, heart, kidney, spleen, plasma, urine, and feces) was measured by inductively coupled plasma mass spectrometry. Transmission electron microscopy (and electron energy loss spectroscopy analysis of metallic deposits) was used to investigate the presence and localization of Gd deposits in the skin. Relaxometry was used to evaluate the presence of dissociated Gd in the skin, liver, and bone. Skin histopathology was performed to investigate the presence of nephrogenic systemic fibrosis-like lesions. Gadodiamide administrations were associated with high morbidity-mortality but also with macroscopic and microscopic skin lesions in renally impaired rats. No such effects were observed with gadopiclenol, gadoterate, or gadobutrol. Overall, elemental Gd concentrations were significantly higher in gadodiamide-treated rats than in rats treated with the other GBCAs for all tissues except the liver (where no significant difference was found with gadopiclenol) and the kidney and the heart (where statistically similar Gd concentrations were observed for all GBCAs). No plasma biochemical abnormalities were observed with gadopiclenol or the control GBCAs. Histopathology revealed a normal skin structure in the rats treated with gadopiclenol, gadoterate, and gadobutrol, contrary to those treated with gadodiamide. No evidence of Gd deposits on collagen fibers and inclusions in fibroblasts was found with gadopiclenol and its macrocyclic controls, unlike with gadodiamide. Animals of all test groups had Gd-positive lysosomal inclusions in the dermal macrophages. However, the textures differed for the different products (speckled texture for gadodiamide and rough-textured appearance for the 2 tested macrocyclic GBCAs). No evidence of biochemical toxicity or pathological abnormalities of the skin was observed, and similar to other macrocyclic GBCAs, gadoterate and gadobutrol, tissue retention of Gd was found to be low (except in the liver) in renally impaired rats treated with the new high-relaxivity GBCA gadopiclenol.

Effects of Methanolic Extract Based-Gel From Saudi Pomegranate Peels With Enhanced Healing Potential on Excision Wounds in Diabetic Rats.

Introduction: Current study was designed to evaluate the wound healing activity of a Saudi pomegranate peel extract on excision wound healing in experimentally induced diabetes in rats. Methodology: Animals were divided into three groups: diabetic excision wound with no treatment, diabetic excision wound with gel alone and diabetic excision wound with Saudi pomegranate peel extract in gel. Animals were monitored for clinical signs, weekly body weight, morbidity and mortality during entire study period. The efficacy parameters evaluated were percent wound contraction, Hydroxyproline content, estimation of Transforming Growth Factor ß1 (TGF-ß1), Vascular Endothelial Growth Factor (VEGF), and Epidermal Growth Factor (EGF) in wound lysates by ELISA, mRNA expression of TGF-ß1, VEGF, and EGF in wound lysates by qPCR, Estimation of nitric oxide (NO) and NO synthase (NOS) in Wound Lysates and histopathology of skin for reepithelization, neovascularization, and inflammation. Results: The Saudi pomegranate peel extract in gel (5.0 g extract per 100 g gel) showed significant wound healing activity when compared to the vehicle control [p < 0.05] following 21 days of treatment. Animals in the control and treatment groups were apparently normal through the study with no significant differences in body weights between groups. Expression of mRNA of TGFβ1, EGF and VEGF in wounds was the highest on day 14 post treatment 4.3, 3.5 and 0.9 fold higher respectively in the treatment group when compared to vehicle control, and on day 21, the values were 0.12, 0.3 and 0.83, respectively. No statistically significant differences were observed in TGF-ß1 levels in wounds on days 4, 7, 14 and 21 post treatment when compared to the vehicle control (p > 0.05). Significantly higher levels of VEGF were observed in treatment group on day 7 and 21 when compared to vehicle control (p < 0.05). Significantly higher levels of EGF were observed in treatment group on day 7 and 21 when compared to vehicle control (p < 0.05). Mean hydroxyproline levels were higher in treatment group on days 4 and 7 when compared to vehicle control. NO levels in treatment group were significantly lower on days 7, 14 and 21 when compared to vehicle control (p < 0.05). NOS activity in treatment group were significantly lower on days 4 and 7 when compared to vehicle control (p < 0.05). Histopathological changes in skin wound in the treatment group were consistent with wound healing when compared to the vehicle group. Conclusion: This study’s findings suggest that topical application of SPPE gel effectively enhanced wound healing in experimentally induced diabetic conditions.

Protection effects of rice protein hydrolysate on UVB-irradiated photodamage in Hartley guinea pigs skin and human skin fibroblasts

Abstract This study examined the ameliorative effects of rice protein hydrolysate (RPH) on UVB irradiation-induced photodamage in Hartley guinea pigs, particularly its influence on antioxidant indicators, moisture content, hydroxyproline (HYP) content and skin histopathology. The molecular mechanisms of RPH characteristic peptides Leu-Leu-Lys (LLK), Leu-Pro-Lys (LPK), and pyroGlu-Lys (pEK) were explored, and the results showed that RPH improved antioxidant capacity, prevented the loss of both water and HYP, and provided effective protection to the skin tissue. LPK and pEK increased the expression of type I collagen by regulating the AP-1/MMP-1 (pEK) and TGF-β/Smad (LPK) signaling pathways, with the LPK exhibiting the most significant effect. These findings indicate that RPH and its characteristic peptides can play vital roles in skin protection and, thus, this study provides a theoretical basis for RPH to become a novel, functional cosmetic ingredient.

JAAD Game Changers∗: Diagnosis of deep cutaneous fungal infections: Correlation between skin tissue culture and histopathology

JAAD Game Changers∗: Diagnosis of deep cutaneous fungal infections: Correlation between skin tissue culture and histopathology

Global Disparities in Skin Cancer Services at HIV Treatment Centers across 29 Countries

Global Disparities in Skin Cancer Services at HIV Treatment Centers across 29 Countries

Dermoscopy in Leprosy: A Clinical and Histopathological Correlation Study

Leprosy, an insidious infectious granulomatous disease, is diagnosed traditionally through clinical examination coupled with skin smears and histopathology. It has myriad clinical presentations that pose diagnostic challenges. Lately, dermoscopy has emerged as a rapid, noninvasive diagnostic modality for many dermatoses. We evaluated the dermoscopic findings of various manifestations of leprosy and correlated them with clinical and histopathological features. This prospective, cross-sectional study was conducted in our skin outpatient department for a period of 1 year. Patients newly diagnosed as having leprosy or those undergoing leprosy treatment for less than 6 months were included. The most representative lesion was dermoscopically evaluated and later biopsied. We included 73 patients in the study. Results indicated an obvious correlation between dermoscopic findings and histopathology. We noted orangish yellow and white structureless areas, steadily throughout the spectrum, depicting dermal granuloma. Additionally, we observed focal vascular structures such as branching, linear, and crown vessels that result from the pressure of granuloma pushing the dilated vessels upwards. The relative absence of skin appendages aided in differentiating leprosy from other granulomatous disorders. Novel findings of our study were the detection of a branch-like pattern of clofazimine-induced pigmentation on dermoscopy and orange globules on onychoscopy. Other unique findings included violaceous structureless areas, characteristic large telangiectatic vessels, follicular plugging, star-shaped silvery-white scaling, and white globules in type 1 reaction; white shiny steaks were observed in patients with borderline lepromatous leprosy, and central white dots and keratotic plugs were observed in patients with histoid leprosy. Dermoscopy, as a noninvasive modality, could aid in the quick diagnosis of leprosy and should be used as a handy tool to complement other investigative tools for this disease.

A novel histopathological scoring system to distinguish urticarial vasculitis from chronic spontaneous urticaria.

BackgroundUrticarial vasculitis (UV) is defined by long‐lasting urticarial lesions combined with the histopathologic findings of leukocytoclastic vasculitis. As one of the major unmet needs in UV, diagnostic criteria are rather vague and not standardized. Moreover, there seems to be considerable overlap with chronic spontaneous urticaria (CSU), particularly for the normocomplementemic variant of UV. Therefore, this study aimed to develop a diagnostic scoring system that improves the histopathologic discrimination between UV and CSU.MethodsLesional skin sections of patients with clinical and histopathologic diagnosis of UV (n = 46) and CSU (n = 51) were analyzed (blinded to the diagnosis) for the following pre‐defined criteria: presence of leukocytoclasia, erythrocyte extravasation, fibrin deposits, endothelial cell swelling, ectatic vessels, blurred vessel borders, dermal edema, intravascular neutrophil, and eosinophil numbers and numbers of dermal neutrophils, macrophages and mast cells.ResultsThe greatest differences between UV and CSU samples were observed for leukocytoclasia (present in 76% of UV vs. 3.9% of CSU samples; p < 0.0001), erythrocyte extravasation (present in 41.3% of UV vs. 2.0% of CSU samples; p < 0.0001), and fibrin deposits (present in 27.9% of UV vessels vs. 9.7% of CSU vessels; p < 0.0001). Based on these findings, we developed a diagnostic score, the urticarial vasculitis score (UVS), which correctly assigned 37 of 46 cases of UV and 49 of 51 cases of CSU to the previously established diagnosis.ConclusionOur results suggest that the UVS, a combined quantitative assessment of the three criteria leukocytoclasia, fibrin deposits and extravasated erythrocytes, distinguishes UV from CSU in skin histopathology. The UVS, if validated in larger patient samples, may help to improve the diagnostic approach to UV.

Influence of Caralluma adscendens Var. attenuata cold cream on UV-B damaged skin epidermal cells: a novel approach.

The online version contains supplementary material available at 10.1007/s13205-021-02694-y.

Effects of mineral complex material treatment on 2,4- dinitrochlorobenzene-induced atopic dermatitis like-skin lesions in mice model

BackgroundAtopic dermatitis (AD) is a chronic allergic inflammatory skin disease characterized by complex pathogenesis including skin barrier dysfunction, immune-redox disturbances, and pruritus. Prolonged topical treatment with medications such as corticosteroids, calcineurin inhibitors, and T-cell inhibitors may have some potential side-effects. To this end, many researchers have explored numerous alternative therapies using natural products and mineral compounds with antioxidant or immunomodulatory effects to minimize toxicity and adverse-effects. In the current study, we investigated the effects of mineral complex material (MCM) treatment on 2, 4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in SKH-1 hairless mice.MethodsAnimals were divided into four groups; normal control (NC), negative control treated with DNCB only (DNCB only), positive control treated with DNCB and tacrolimus ointment (PC) and experimental group treated with DNCB and MCM patch (MCM). Skin inflammation and lesion severity were investigated through analyses of skin parameters (barrier score and strength, moisture and trans-epidermal water loss level), histopathology, immunoglobulin E, and cytokines. In addition, reactive oxygen species (ROS), nitric oxide (NO), glutathione peroxidase (GPx), and catalase (CAT) levels were measured in both serum and skin lysate.ResultsOur results demonstrates that MCM patch improved the progression of AD-like skin lesions by significantly increasing skin barrier strength and decreasing trans-epidermal water loss. Additionally, dermal administration of MCM patch significantly reduced epidermal thickness, ROS, and NO levels in skin lysate. Furthermore, we found that MCM suppressed the levels of AD-involved (Th1 and Th2) cytokines such as IL-2, IFN-γ, and IL-4 in blood. In addition, the levels of other Th1, and Th2 and inflammatory cytokines such as IL-1β, TNF-α, IL-6, IL-12(p70) and IL-10 were found lowest in the MCM group than in the DNCB only and PC groups. Moreover, we found total serum IgE level significantly increased after DNCB treatment, but decreased in the PC and MCM groups.ConclusionTaken together, our findings suggest that MCM application may have beneficial effects either systemic or regional on DNCB-induced AD lesional skin via regulation of the skin barrier function and immune-redox response.

Early immune responses in skin and lymph node after skin delivery of Toll-like receptor agonists in neonatal and adult pigs

The skin is potentially an important vaccine delivery route facilitated by a high number of resident antigen presenting cells (APCs), which are known to be stimulated by different Toll-like receptor agonists (TLRa). In this study, neonatal and adult pigs were vaccinated in the skin using dissolving microneedle patches to investigate the immuno-stimulatory potential of different TLRa and possible age-dependent differences early after vaccination. These patches contained TLR1/2a (Pam3Cys), TLR7/8a (R848) or TLR9a (CpG ODN) combined with inactivated porcine reproductive and respiratory syndrome virus (PRRSV) or with an oil-in-water stable emulsion. Vaccinated skin and draining lymph nodes were analysed for immune response genes using microfluidic high-throughput qPCR to evaluate the early immune response and activation of APCs. Skin pathology and immunohistochemistry were used to evaluate the local immune responses and APCs in the vaccinated skin, respectively.In both neonatal and adult pigs, skin vaccination with TLR7/8a induced the most prominent early inflammatory and immune cell responses, particularly in the skin. Skin histopathology and immunohistochemistry of APCs showed comparable results for neonatal and adult pigs after vaccination with the different TLRa vaccines. However, in vaccinated neonatal pigs in the skin and draining lymph node more immune response related genes were upregulated compared to adult pigs. We showed that both neonatal and adult skin could be stimulated to develop an immune response, particularly after TLR7/8a vaccination, with age-dependent differences in regulation of immune genes. Therefore, age-dependent differences in local early immune responses should be considered when developing skin vaccines.