Epidermal Lesions Research Articles

Integrated analysis of miRNA-mRNA networks reveals a strong anti-skin cancer signature in vitiligo epidermis.

Expression of microRNAs (miRNAs) is often dysregulated in several cancers, including non-melanoma skin cancer (NMSC). Individuals with vitiligo possess a deregulated miRnome along with a lower risk of developing NMSCs. We used data sets from our previously published studies on vitiligo epidermis to construct functional miRNA-mRNA networks to understand the molecular basis underlying the lower incidence of NMSC observed in individuals with vitiligo. miRTarBase database was used to fetch the experimentally validated targets of differentially expressed miRNAs and two protein-protein interaction (PPI) networks were constructed for the miRNA-mRNA interactions (230 downregulated targets of 5 upregulated miRNAs and 47 upregulated mRNAs targeted by 12 downregulated miRNAs). Pathway enrichment analysis identified RNA biogenesis and transport as well as cell adhesion to be perturbed in vitiligo. Further, oncogenic transcription factors (OTFs) that were upregulated in publicly available squamous cell carcinoma (SCC) or basal cell carcinoma (BCC) microarray data were compared with that of vitiligo to decode skin cancer-specific molecular signatures. We identified three significantly upregulated miRNAs, miR-31-5p, miR-31-3p and miR-194-3p in lesional epidermis that could negatively regulate seven oncogenic transcription factors, FOXC1, AR, SP1, YY1, GLI2, TP53 and RARA, known to be over-expressed in SCC or BCC. Taken together, our study identified a perturbed miRNA-regulated transcriptome, which potentially confers protection to vitiligo skin from an increased incidence of NMSC.

Histological Characteristics of Skin Treated With a Fractionated 1064-nm Nd: YAG Picosecond Laser With Holographic Optics.

Picosecond lasers (PSL) constitute a significant technological advancement and exert rejuvenating effects upon the skin. This study was conducted to investigate changes in the skin upon treatment with the fractionated 1064-nm Nd: YAG PSL through in vivo and ex vivo human histological analysis. In vivo back skin specimens were treated with a fractionated 1064-nm PSL at 1.3, 2.1, and 2.9 mJ fluence for two passes, and 2.9 mJ for 10 passes, and then stained with hematoxylin and eosin (H&E). Ex vivo foreskin specimens after circumcision surgery were treated with a PSL at 1.3, 2.1, and 2.9 mJ fluence for two and 10 passes, followed by H&E staining. Ex vivo skin tissue sections treated with a PSL at 2.9 mJ fluence for 10 passes were also immunostained for Melan-A and CD31. Intraepidermal vacuoles were observed, along with pigment accumulation and inflammatory cell infiltration in the vacuoles at 24 hours after PSL treatment in the in vivo skin specimens. The vacuoles expanded as the fluence increased. Numerous intraepidermal vacuoles were observed, with dermal hemorrhage and inflammatory cell infiltration upon high-fluence, multi-pass PSL treatment in the in vivo skin specimens. PSL treatment yielded both epidermal and dermal vacuoles in ex vivo skin specimens. Melan-A-positive cells were seen in the cystic wall of vacuoles in the epidermal basal layer, whereas CD31-positive cells were detected in the cystic wall of some dermal vacuoles. The fractionated 1064-nm PSL produced epidermal vacuoles and dermal lesions, with histological differences between the in vivo and ex vivo skin specimens. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.

Cutting Edge of the Pathogenesis of Atopic Dermatitis: Sphingomyelin Deacylase, the Enzyme Involved in Its Ceramide Deficiency, Plays a Pivotal Role.

Atopic dermatitis (AD) is characterized clinically by severe dry skin and functionally by both a cutaneous barrier disruption and an impaired water-holding capacity in the stratum corneum (SC) even in the nonlesional skin. The combination of the disrupted barrier and water-holding functions in nonlesional skin is closely linked to the disease severity of AD, which suggests that the barrier abnormality as well as the water deficiency are elicited as a result of the induced dermatitis and subsequently trigger the recurrence of dermatitis. These functional abnormalities of the SC are mainly attributable to significantly decreased levels of total ceramides and the altered ceramide profile in the SC. Clinical studies using a synthetic pseudo-ceramide (pCer) that can function as a natural ceramide have indicated the superior clinical efficacy of pCer and, more importantly, have shown that the ceramide deficiency rather than changes in the ceramide profile in the SC of AD patients plays a central role in the pathogenesis of AD. Clinical studies of infants with AD have shown that the barrier disruption due to the ceramide deficiency is not inherent and is essentially dependent on postinflammatory events in those infants. Consistently, the recovery of trans-epidermal water loss after tape-stripping occurs at a significantly slower rate only at 1 day post-tape-stripping in AD skin compared with healthy control (HC) skin. This resembles the recovery pattern observed in Niemann–Pick disease, which is caused by an acid sphingomyelinase (aSMase) deficiency. Further, comparison of ceramide levels in the SC between before and after tape-stripping revealed that whereas ceramide levels in HC skin are significantly upregulated at 4 days post-tape-stripping, their ceramide levels remain substantially unchanged at 4 days post-tape-stripping. Taken together, the sum of these findings strongly suggests that an impaired homeostasis of a ceramide-generating process may be associated with these abnormalities. We have discovered a novel enzyme, sphingomyelin (SM) deacylase, which cleaves the N-acyl linkage of SM and glucosylceramide (GCer). The activity of SM deacylase is significantly increased in AD lesional epidermis as well as in the involved and uninvolved SC of AD skin, but not in the skin of patients with contact dermatitis or chronic eczema, compared with HC skin. SM deacylase competes with aSMase and β-glucocerebrosidase (BGCase) to hydrolyze their common substrates, SM and GCer, to yield their lysoforms sphingosylphosphorylcholine (SPC) and glucosylsphingosine (GSP), respectively, instead of ceramide. Consistently, those reaction products (SPC and GSP) accumulate to a greater extent in the involved and uninvolved SC of AD skin compared with chronic eczema or contact dermatitis skin as well as HC skin. Successive chromatographies were used to purify SM deacylase to homogeneity with a single band of ≈43 kDa and with an enrichment of >14,000-fold. Analysis of a protein spot with SM deacylase activity separated by 2D-SDS-PAGE using MALDI-TOF MS/MS allowed its amino acid sequence to be determined and to identify it as the β-subunit of acid ceramidase (aCDase), an enzyme consisting of α- and β-subunits linked by amino-bonds and a single S-S bond. Western blotting of samples treated with 2-mercaptoethanol revealed that whereas recombinant human aCDase was recognized by antibodies to the α-subunit at ≈56 and ≈13 kDa and the β-subunit at ≈43 kDa, the purified SM deacylase was detectable only by the antibody to the β-subunit at ≈43 kDa. Breaking the S-S bond of recombinant human aCDase with dithiothreitol elicited the activity of SM deacylase with an apparent size of ≈40 kDa upon gel chromatography in contrast to aCDase activity with an apparent size of ≈50 kDa in untreated recombinant human aCDase. These results provide new insights into the essential role of SM deacylase as the β-subunit aCDase that causes the ceramide deficiency in AD skin.

Squamous Cell Carcinoma in a Group of Solomon Island Leaf Frogs (Ceratobatrachus guentheri)

Between 2015 and 2016, 16 adult Solomon Island leaf frogs (Ceratobatrachus guentheri) were evaluated at a zoological institution for proliferative epidermal lesions on the head, and occasionally the dorsum and limbs. In most cases, the lesions were severe enough that they could not be surgically resected. Five frogs were diagnosed histologically with proliferative epidermal lesions consistent with squamous cell carcinoma. Polymerase chain reaction for herpesvirus, papillomavirus, and chytridiomycosis yielded negative results. Transmission electron microscopy and virus isolation of two masses did not identify a virus. Although no specific etiology could be identified, based on the clinical presentation, the number of animals affected, and the negative test results for viral agents, an environmental, husbandry, or genetic component were considered as possible etiologies.

Role of CYR61 in psoriatic lesional and perilesional skin: A clinical and immunohistochemical study.

Psoriasis is considered as an immune-mediated disorder with significant epidermal hyperplasia and inflammation. Cysteine-rich angiogenic inducer 61 (CYR61), known as CCN family member 1 (CCN1), plays an important role in cell proliferation and neovascularization which may trigger psoriasis development. This study aimed to assess the immunostaining of CYR61 in psoriatic skin (lesional and perilesional) compared to control skin. This is a case-control study. The Psoriasis Area and Severity Index (PASI) was used to evaluate disease severity. A punch biopsy was taken from psoriatic skin lesions (30), perilesional (30) skin, and matched site of controls (20). The pathological and immunostaining assessments of CYR61 were conducted. There was a significant gradual progressive overexpression of CYR61 in keratinocytes from control skin to perilesional and lesional psoriatic skin (P=.00). Moreover, lesional psoriatic skin showed overexpression of CYR61 in inflammatory cells in the dermis than controls. CYR61 expression (lesional epidermis) revealed a significant positive correlation with the PASI score (r=.63; P=.00). There was a significant relationship between intensity and H-core of CYR61 in the lesional psoriatic epidermis with joint affection. CYR61 may trigger epidermal hyperplasia and potentiate inflammatory infiltration in psoriasis vulgaris patients, and therapies targeting CYR61 may be effective in the management of psoriasis vulgaris.

Suppression of IL-17A-induced CCL20 production by cytokine inducible SH2-containing protein 1 in epidermal keratinocytes

BackgroundLesions of atopic dermatitis have fewer Th17 cells than those of psoriasis, resulting in frequent skin infections. Expression of CCL20, a chemokine that is important for recruiting Th17 cells, is suppressed in the lesions of atopic dermatitis. We previously reported that IL-4 induces the expression of cytokine-inducible SH2-containing protein 1 (CIS1), a member of the CIS/SOCS family, in epidermal keratinocytes. ObjectiveTo investigate whether CIS1 influences CCL20 production in epidermal keratinocytes. MethodsExpression of CIS1 was examined in atopic dermatitis skin and in cultured keratinocytes. The effects of overexpression of CIS1 on CCL20 production by IL-17A, and on signaling pathways inhibited by CIS1, were assessed in vitro. ResultsExpression of CIS1 was enhanced in the basal layer of the lesional epidermis of skin with atopic dermatitis. When CIS1 was expressed in keratinocytes using adenoviral vectors, IL-17A-induced CCL20 expression, but not HBD2 or S100A7 expression, was significantly suppressed. TNF-α/IL-1-induced CCL20 production was not altered by CIS1. Overexpression of CIS1 attenuated IL-17A-induced ERK phosphorylation. ERK phosphorylation was mediated by the Act1 and Src family kinase pathways. CIS1 overexpression suppressed Src phosphorylation. Among the Src family kinases, the Yes kinase may have an important role because knockdown of Yes in epidermal keratinocytes resulted in suppression of ERK phosphorylation and CCL20 mRNA expression by IL-17A. ConclusionCIS1 induced by Th2 cytokines has the ability to change the response of epidermal keratinocytes to IL-17A by suppression of Src family kinases.

Palmoplantar Keratoderma: Rare Case Report

Palmoplantar keratodermas(PPK) are group of cornification disorders characterized by epidermal hyperkeratotic lesions involving the palms and soles. A 50years old healthy male, presented with history of multiple punctate hyperkeratotic papules since last 5 years.

The long noncoding RNA MALAT1 suppresses miR-211 to confer protection from ultraviolet-mediated DNA damage in vitiligo epidermis by upregulating sirtuin 1.

The absence of melanocytes poses a challenge for long-term tissue homeostasis in vitiligo. Surprisingly, while individuals with Fitzpatrick phototypes I-II (low melanin content) have a higher incidence of melanoma and nonmelanoma skin cancer, people with vitiligo are at a decreased risk for the same. To understand the molecular mechanisms that protect vitiligo skin from ultraviolet (UV)-induced DNA damage by (i) characterizing differentially expressed microRNAs in lesional vs. nonlesional epidermis and (ii) identifying their upstream regulators and downstream gene targets. Genome-wide microRNA profiling of nonlesional and lesional epidermis was performed on five individuals with stable nonsegmental vitiligo using next-generation RNA sequencing. The relevance of the upstream regulator and downstream target gene of the most differentially expressed microRNA was studied. Our study found sirtuin1 (SIRT1), an NAD-dependent deacetylase, to be a direct target of miR-211 - the most significantly downregulated microRNA in lesional epidermis. Inhibition of SIRT1 with EX-527 downregulated keratin 10 and involucrin, suggesting that SIRT1 promotes keratinocyte differentiation. Overexpression of miR-211 mimic led to a significant increase in γ-H2AX positivity and cyclobutane pyrimidine dimer (CPD) formation, hallmarks of UVB-mediated DNA damage. These effects could be ameliorated by the addition of resveratrol, a SIRT1 activator. Furthermore, a long noncoding RNA, MALAT1, was identified as a negative upstream regulator of miR-211. Overexpression of MALAT1 resulted in increased expression of SIRT1 and a concomitant removal of UVB-induced CPDs in primary keratinocytes. These findings establish a novel MALAT1-miR-211-SIRT1 signalling axis that potentially confers protection to the 'amelanotic' keratinocytes in vitiligo.

Insidental olarak saptanan dermatofibrosarkom protuberans tedavisi: Tek merkez 5 yıllık deneyimlerimiz

Aim: Dermatofibrosarcoma protuberans (DFSP) is a rare skin tumor. The diagnosis is challenging because it is usually hard to differ DFSP from other skin lesions. Distant metastasis is rare, but local recurrence is common.The aim of this study is to review the treatment algorithms in DFSPs that are detected incidentally and to increase awareness about this rare tumor.
 Material and Methods: 17 patients who underwent excision of epidermal lesions which were considered to be benign and were diagnosed with DFSP, at departmant of general surgery between 2012 and 2017, were analyzed.
 Result: A total of 17 patients were analyzed retrospectively. No recurrence was detected in any of ourpatients.
 Conclusion: Awareness of this rare entity is important for diagnosis and management of the disease.

MiR-155 Contributes to Normal Keratinocyte Differentiation and Is Upregulated in the Epidermis of Psoriatic Skin Lesions.

The role of microRNAs (miRNAs) during keratinocyte (KC) differentiation and in skin diseases with epidermal phenotypes has attracted strong interest over the past few years. However, combined mRNA and miRNA expression analyses to elucidate the intricate mRNA–miRNA networks of KCs at different stages of differentiation have not been performed yet. In the present study, we investigated the dynamics of miRNA and mRNA expression during KC differentiation in vitro and in normal and psoriatic epidermis. While we identified comparable numbers of up- and downregulated mRNAs (49% and 51%, respectively), miRNAs were predominantly upregulated (76% vs 24%) during KC differentiation. Further bioinformatics analyses suggested an important inhibitory role for miR-155 in KC differentiation, as it was repressed during KC differentiation in normal skin but strongly upregulated in the epidermis of psoriatic skin lesions. Mimicking the inflammatory milieu of psoriatic skin in vitro, we could show that the pro-inflammatory cytokines IL17, IL1β and INFγ synergistically upregulated miR-155 expression in KCs. Forced over-expression of miR-155 in human in vitro skin models specifically reduced the expression of loricrin (LOR) in KCs, indicating that miR-155 interferes with the establishment of a normal epidermal barrier. Together, our data indicate that downregulation of miR-155 during KC differentiation is a crucial step for epidermal barrier formation. Furthermore, its strong upregulation in psoriatic lesions suggests a contributing role of miR-155 in the altered keratinocyte differentiation observed in psoriasis. Therefore, miR-155 represents as a potential target for treating psoriatic skin lesions.

Role of 11\u03b2-hydroxysteroid dehydrogenase type 1 in the development of atopic dermatitis

Glucocorticoids (GCs) are potent anti-inflammatory drugs, the secretion of which is mediated and controlled by the hypothalamic–pituitary–adrenal axis. However, they are also secreted de novo by peripheral tissues for local use. Several tissues express 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), including the skin. The inactive GC cortisone is converted by 11β-HSD1 to active GC cortisol, which is responsible for delayed wound healing during a systemic excess of GC. However, the role of 11β-HSD1 in inflammation is unclear. We assessed whether 11β-HSD1 affects the development of atopic dermatitis (AD) in vitro and in vivo. The expression of 11β-HSD1 in the epidermis of AD lesions was higher than that in the epidermis of healthy controls. Knockdown of 11β-HSD1 in human epidermal keratinocytes increased the production of thymic stromal lymphopoietin. In an oxazolone-induced mouse model of AD, localized inhibition of 11β-HSD1 aggravated the development of AD and increased serum cytokine levels associated with AD. Mice with whole-body knockout (KO) of 11β-HSD1 developed significantly worse AD upon induction by oxazolone. We propose that 11β-HSD1 is a major factor affecting AD pathophysiology via suppression of atopic inflammation due to the modulation of active GC in the skin.

ZnO NPs delay the recovery of psoriasis-like skin lesions through promoting nuclear translocation of p-NFκB p65 and cysteine deficiency in keratinocytes

BackgroundThis study aimed to evaluate the safety of applying zinc oxide nanoparticles (ZnO NPs) to pathological skin. The majority of previous studies confirmed the safety of applying ZnO NPs to normal skin. However, we know very little about the risks of using sunscreen, cosmetics and topical drugs containing ZnO NPs for individuals with skin diseases. ResultsZnO NPs passed through gaps between keratinocytes and entered stratum basale of epidermis and dermis in imiquimod-induced psoriasis-like skin lesions. Application of a ZnO NP-containing suspension for 3 connective days delayed the healing of the epidermal barrier; increased the expression levels of inflammatory cytokines; promoted keratinocyte apoptosis and disturbed redox homeostasis. In TNF-α-stimulated HaCaT cells, QNZ and JSH-23 (NFκB inhibitors) blocked ZnO NP-induced inflammation. JSH-23 and NAC (a precursor of cysteine) inhibited ZnO NP-induced nuclear translocation of p-NFκB p65, cysteine deficiency and apoptosis. Additionally, ZnO NPs decreased CD98 level in main pathway and failed to activate transsulfuration pathway in cysteine biosynthesis. ConclusionsZnO NPs can enter psoriasis-like skin lesions and promote inflammation and keratinocyte apoptosis through nuclear translocation of p-NFκB p65 and cysteine deficiency. This work reminds the public that ZnO NPs have harmful effects on the recovery of inflammatory skin diseases.

Mobilization of Melanocytes During NB-UVB Treatment of Vitiligo

Abstract Vitiligo, a common skin depigmentation disorder, is the result of complex interactions of genetic, immunological, environmental, and biochemical events. Treatments for vitiligo include drugs, phototherapy, surgical transplantation, and so on. Among them, the efficacy of narrow band-ultraviolet B has been confirmed. By inducing keratinocyte-derived factors and signalings, narrow band-ultraviolet B can trigger and/or promote the mobilization of melanocytes which migrate to lesional epidermis ultimately, leads to the repigmentation of white patches. The mobilization of melanocytes includes stages of activation, migration, proliferation, and differentiation. Elucidating processes that enable the specific mobilization of melanocytes and the signaling pathways and factors involved, will help the development of new drugs and methods for the treatment of vitiligo.

Toxic Epidermal Necrolysis-Like Lesions as Cutaneous Manifestation of Acute Methotrexate Toxicity.

Toxic Epidermal Necrolysis-Like Lesions as Cutaneous Manifestation of Acute Methotrexate Toxicity.

FUT8 Remodeling of EGFR Regulates Epidermal Keratinocyte Proliferation during Psoriasis Development

α-(1,6)-fucosyltransferase 8 (FUT8) is implicated in the pathogenesis of several malignancies, but its role in psoriasis is poorly understood. In this study, we show that FUT8 remodeling of EGFR plays a critical role in the development of psoriasis phenotypes. Notably, elevated FUT8 expression was associated with disease severity in the lesional epidermis of a patient with psoriasis. FUT8 gain of function promoted HaCaT cell proliferation, whereas short hairpin FUT8 reduced cell proliferation and induced a longer S phase with downregulation of cyclin A1 expression. Furthermore, cell proliferation, which is controlled by the activation of EGFR, was shown to be regulated by FUT8 core fucosylation of EGFR. Short hairpin FUT8 significantly reduced EGFR/protein kinase B signaling and slowed EGF‒EGFR complex trafficking to the perinuclear region. Moreover, short hairpin FUT8 reduced ligand-induced EGFR dimerization. Overactivated EGFR was observed in the lesional epidermis of both human patient and psoriasis-like mouse model, whereas conditional knockout of FUT8 in an IL-23 psoriasis-like mouse model ameliorated disease phenotypes and reduced EGFR activation in the epidermis. These findings implied that elevated FUT8 expression in the lesional epidermis is implicated in the development of psoriasis phenotypes, being required for EGFR overactivation and leading to keratinocyte hyperproliferation.

Effects of the Association between Photobiomodulation and Hyaluronic Acid Linked Gold Nanoparticles in Wound Healing.

Healing is the process responsible for restoring the integrity of the body's internal or external structures when they rupture. Photobiomodulation (PBM) stands out as one of the most efficient resources in the treatment of epithelial lesions, as well as hyaluronic acid (HA), which has been emerging as a new molecule for the treatment of dermal and epidermal lesions. The biological application of gold nanoparticles (GNPs) shows promising results. This study aimed to investigate the possible anti-inflammatory and antioxidant effects of the association between PBM and GNPs-linked HA in an epithelial lesion model. Fifty Wistar rats were randomly distributed in the Control Group (CG); (PBM); (PBM + HA); (PBM + GNPs); (PBM + GNPs-HA). The animals were anesthetized, trichotomized, and induced to a surgical incision in the dorsal region. Topical treatment with HA (0.9%) and/or GNPs (30 mg/kg) occurred daily associated with 904 nm laser irradiation, dose of 5 J/cm2, which started 24 h after the lesion and was performed daily until the seventh day. The levels of proinflammatory (IL1 and TNFα), anti-inflammatory (IL10 and IL4) and growth factors (FGF and TGFβ) cytokines and oxidative stress parameters were evaluated, besides histological analysis through inflammatory infiltrate, fibroblasts, new vessels, and collagen production area. Finally, for the analysis of wound size reduction, digital images were performed and subsequently analyzed by the IMAGEJ software. The treated groups showed a decrease in proinflammatory cytokine levels and an increase in anti-inflammatory cytokines. TGFβ and FGF levels also increased in the treated groups, especially in the combination therapy group (PBM + GNPs-HA). Regarding the oxidative stress parameters, MPO, DCF, and Nitrite levels decreased in the treated groups, as well as the oxidative damage (Carbonyl and Thiol groups). In contrast, antioxidant defense increased in the groups with the appropriate therapies proposed compared to the control group. Histological sections were analyzed where the inflammatory infiltrate was lower in the PBM + GNPs-HA group. The number of fibroblasts was higher in the PBM and PBM + HA treated groups, whereas collagen production was higher in all treated groups. Finally, in the analysis of the wound area contraction, the injury group presented a larger area in cm2 compared to the other groups. Taken together, these results allow us to observe that the combination of PBM + GNPs-HA optimized the secretion of anti-inflammatory cytokines, proliferation and cell differentiation growth factors, and made an earlier transition to the chronic phase, contributing to the repair process.

Galectin-8 Is Upregulated in Keratinocytes by IL-17A and Promotes Proliferation by Regulating Mitosis in Psoriasis

Psoriasis is a chronic inflammatory skin disease that develops under the influence of the IL-23/T helper 17 cell axis and is characterized by intense inflammation and prominent epidermal hyperplasia. In this study, we demonstrate that galectin-8, a β-galactoside‒binding lectin, is upregulated in the epidermis of human psoriatic skin lesions as well as in a mouse model of psoriasis induced by intradermal IL-23 injections and in IL-17A‒treated keratinocytes. We show that keratinocyte proliferation is less prominent in galectin-8‒knockout mice after intradermal IL-23 treatment than in wild-type mice. In addition, we show that galectin-8 levels in keratinocytes are positively correlated with the ability of the cells to proliferate and that transitioning from mitosis into G1 phase is delayed in galectin-8‒knockout HaCaT cells after cell-cycle synchronization and release. We demonstrate by immunofluorescence staining and immunoblotting the presence of galectin-8 within the mitotic apparatus. We reveal by coimmunoprecipitation and mass spectrometry analysis that α-tubulin interacts with galectin-8 during mitosis. Finally, we show that in the absence of galectin-8, pericentrin compactness is lessened and mitotic microtubule length is shortened, as demonstrated by immunofluorescence staining. We conclude that galectin-8 is upregulated in psoriasis and contributes to the hyperproliferation of keratinocytes by maintaining centrosome integrity during mitosis through interacting with α-tubulin.

APRIL expression is upregulated in atopic dermatitis skin lesions and at sites of antigen driven allergic skin inflammation in mice

Atopic dermatitis (AD) is the most common inflammatory skin disease. It is characterized by a defective skin barrier and a Th2 dominated skin inflammation. The TNF family member a proliferation-inducing ligand (APRIL) and its receptors transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B cell maturation antigen (BCMA) are expressed by immune cells and epithelial cells including keratinocytes. We demonstrate that APRIL expression is upregulated in the epidermis of skin lesions from patients with AD as well as in mouse skin undergoing allergic inflammation elicited by epicutaneous (EC) sensitization with the antigen ovalbumin. We show that APRIL from OVA sensitized mouse skin causes keratinocytes to upregulate the expression of IL-6, an inflammatory cytokine implicated in AD pathogenesis. These results suggest a role for APRIL in allergic skin inflammation and a potential role for APRIL blockade in treating AD.

Evaluation of Anaesthetic Protocol for Zebrafish Embryo (Danio rerio): Lignocaine Combined with Diazepam and Ketamine with different doses Temperature Modulation

Zebrafish (Danio rerio) model is economically viable and scientifically significant to identify several human diseases. It has genetic homology to humans (80-85%). Its other advantages are high reproductive success, embryo and larvae transparency and rapid development. Also compared to mammals, the maintenance cost of Zebrafish is lower . Ethyl 3-aminobenzoate methane sulfonate (MS-222) is known as the standard fish Anaesthetic and widely used in Zebrafish, but it can have adverse effects depending on the dose and exposure like aversion, stress induction, epidermal and corneal lesions, respiratory acidosis, hypoxemia, decreased heart rate and death. To reduce such adverse effect new anaesthetic protocol is required. In this experiment, Diazepam is taken as the test drug because of a sedative-hypnotic drug with anticonvulsant properties, similarly Lignocaine as a local Anaesthetics and Ketamine as a rapid acting general Anaesthetic along with for all cases temperature modulation has an important role. During this evaluation, some levels of Anaesthesia are found in fish like normal, Deep and light sedation, Narcosis, Anaesthesia and Medullary collapse (Death). In this observation, we have to closely observe the Spontaneous movement, Muscle tone, Reflex response, and Tactile stimuli and balance respiratory rate, consciousness levels of the fish. Onset of action KETAMINE and DIAZAPAM is almost same but LIGNOCANE is lower by observing heartbeat after treatment we can see that the effect of DIAZAPAM is much lesser in compared with LIGNOCAINE and KETAMINE In comparison with LIGNOCAINE and KETAMINE, LIGNOCAINE is better than KETAMINE. Comparing to the time of shock 40 second of shock with drug is least effective.60 second of shock is most effective in all drug and dose combination. Keywords: Anaesthesia, Zebrafish, Embryo, Lignocaine, Diazepam, Ketamine, Temperature Cite this Article Samrat Bose, GouravSamajdar. Evaluation of Anaesthetic Protocol for Zebrafish Embryo (Daniorerio): Lignocaine Combined with Diazepam and Ketamine with different doses Temperature Modulation. Research & Reviews: A Journal of Drug Formulation, Development and Production . 2020; 7(2): 15–31p.

Uncovering the mechanism of Jueyin granules in the treatment of psoriasis using network pharmacology

Ethnopharmacological relevanceOur clinical practice demonstrated that Jueyin granules (JYG) benefit patients with mild to moderate psoriasis vulgaris without apparent adverse effects. JYG have been shown to inhibit epidermal proliferation in an imiquimod (IMQ)-induced psoriasis-like mouse model, as well as keratinocyte proliferation. Moreover, JYG causes no acute or chronic toxicity in animal models. However, its related molecular mechanism has still not been elucidated. Aim of the studyTo assess the mechanism of JYG against psoriasis. Materials and methodsThis study combined network pharmacology analysis with experiments to investigate the mechanism of JYG against psoriasis. First, the molecular docking technology was used to construct the network of medicinal materials-core active plant ingredients-core targets and identify possible drug targets. Next, high-performance liquid chromatography (HPLC) was used for quality control of JYG. Finally, a mice model of psoriasis was used to further verify the effects of JYG. Results(1) Molecular docking analysis of network pharmacology revealed that the therapeutic effects of JYG on psoriasis might be achieved through Vitamin D Receptor (VDR) effects. (2) The concentrations of chlorogenic acid and paeoniflorin were determined using HPLC to establish quality control of JYG. (3) JYG ameliorated pathological characteristics that included in vivo reductions in erythema, scale, and infiltration scores of back and ear lesions in IMQ-induced psoriasis-like mice. Moreover, a reduced number of PCNA-positive and Ki67-positive cells were observed in the epidermis of JYG-treated lesions. JYG also reduced inflammation (interleukin (IL)-17, IL-23) in the peripheral blood of IMQ-induced psoriasis-like mice. As expected, JYG was found to upregulate VDR expression and downregulate p-STAT3 expression in the IMQ group, which may contribute to its mechanism against psoriasis. ConclusionOverall, this study clarifies the mechanism of JYG against psoriasis and provides evidence to support its clinical use.