Human Beta Defensin-2 mRNA and Proteasome Subunit ß Type 8 mRNA Analysis, Useful in Differentiating Skin Biopsies from Atopic Dermatitis and Psoriasis Vulgaris Patients.

(1): Atopic dermatitis and psoriasis vulgaris are chronic, inflammatory diseases. Clinical presentation usually leads to a proper diagnosis, but sometimes neither clinical examination nor histopathological evaluation can be conclusive. Therefore, we aimed to build up a novel diagnostic tool and check it for accuracy. The main objective of our work was to differentiate between healthy skin (C), atopic dermatitis (AD) and psoriasis vulgaris (PV) biopsies on the base of involucrin (IVL) and human ß-defensin-2 (hBD-2) concentrations and their mRNA, as well as mRNA for TPP2 and PSMB8. (2): ELISA for IVL and hBD-2 proteins and Real-time PCR for the relative expression of mRNA for: IVL (IVL mRNA), hBD-2 (hBD-2 mRNA), PSMB8 (PSMB8 mRNA) and TPP2 (TPP2 mRNA), isolated from skin biopsies taken from AD and PV patients and healthy volunteers were performed. (3): hBD-2 mRNA and PSMB8 mRNA correlated with some parameters of clinical assessment of inflammatory disease severity. hBD-2 mRNA expression, exclusively, was sufficient to distinguish inflammatory skin biopsies from the healthy ones. (4): hBD-2 mRNA and PSMB8 mRNA analysis were the most valuable parameters in differentiating AD and PV biopsies.

N-Acetylcysteine Added to Local Anesthesia Reduces Scar Area and Width in Early Wound Healing-An Animal Model Study.

The aim of the study was to evaluate if a pre-incisional N-acetylcysteine (NAC) treatment altered the process of wound healing in a rat model. The dorsal skin of 24 Sprague-Dawley rats was incised in six locations. Before the incisions were made, skin was injected either with lidocaine and epinephrine (one side) or with these agents supplemented with 0.015%, 0.03%, or 0.045% NAC (contralaterally). Photographic documentation of the wound healing process was made at 11 time points. Rats were sacrificed 3, 7, 14, or 60 days after incision to excise scars for histological analysis. They included: Abramov scale scoring, histomorphometry analysis, and collagen fiber arrangement assessment. Skin pretreated with 0.03% NAC produced the shortest scars at all analyzed time points, though this result was statistically insignificant. At this NAC concentration the scars had smaller areas on the third day and were narrower on the day 4 compared with all the other groups (p < 0.05). On day 7, at the same concentration of NAC, the scars had a higher superficial concentration index (p = 0.03) and larger dermal proliferation area (p = 0.04). NAC addition to pre-incisional anesthetic solution decreased wound size and width at an early stage of scar formation at all concentrations; however, with optimal results at 0.03% concentration.

Single Dose of N-Acetylcysteine in Local Anesthesia Increases Expression of HIF1α, MAPK1, TGFß1 and Growth Factors in Rat Wound Healing.

In this study, we aimed to investigate the influence of N-acetylcysteine (NAC) on the gene expression profile, neoangiogenesis, neutrophils and macrophages in a rat model of incisional wounds. Before creating wounds on the backs of 24 Sprague-Dawley rats, intradermal injections were made. Lidocaine-epinephrin solutions were supplemented with 0.015%, 0.03% or 0.045% solutions of NAC, or nothing (control group). Scars were harvested on the 3rd, 7th, 14th and 60th day post-surgery. We performed immunohistochemical staining in order to visualize macrophages (anti-CD68), neutrophils (anti-MPO) and newly formed blood vessels (anti-CD31). Additionally, RT-qPCR was used to measure the relative expression of 88 genes involved in the wound healing process. On the 14th day, the number of cells stained with anti-CD68 and anti-CD31 antibodies was significantly larger in the tissues treated with 0.03% NAC compared with the control. Among the selected genes, 52 were upregulated and six were downregulated at different time points. Interestingly, NAC exerted a significant effect on the expression of 45 genes 60 days after its administration. In summation, a 0.03% NAC addition to the pre-incisional anesthetic solution improves neovasculature and increases the macrophages' concentration at the wound site on the 14th day, as well as altering the expression of numerous genes that are responsible for the regenerative processes.

[Novel therapies in the treatment of atopic dermatitis]. / Nowoczesne terapie w leczeniu atopowego zapalenia skóry.

Atopic dermatitis is a chronic, inflammatory disease characterized by eczematous lesions in typical locations. It is caused by the complex interplay between genetic predisposition, environmental factors and altered skin barrier. A more precise understanding of the pathogenesis of atopic dermatitis revealed novel therapeutic options. Dupilumab, which long-term effectiveness and safety have been proven, is the first biologic available for atopic dermatitis. Other monoclonal antibodies such as nemolizumab, tralokinumab, lebrikizumab and fezakinumab demonstrated statistically significant clinical improvements in phase 2 and 3 trials. Further investigations are needed to evaluate their longterm efficacy. JAK inhibitors such as abrocitinib, baricitinib and upadacitinib showed promising effects in improvement of skin lesions and itch reduction. Beneficial immunomodulatory effect of JAK inhibitors dissipate relatively quickly with cessation of the drug, because as opposed to monoclonal antibodies, they have short half-lives. Thus, during SARS-CoV-2 infection it might be safer to use JAK inhibitors in case of necessity of a rapid immune response. There is a need to differentiate subtypes of atopic dermatitis, based on clinical symptoms and inflammatory mediators to choose an optimal therapeutic option for each patient.

Anti-Interleukin-31 Receptor A Antibody for Atopic Dermatitis.

BACKGROUND: Interleukin-31 may play a role in the pathobiologic mechanism of atopic dermatitis and pruritus. We wanted to assess the efficacy and safety of nemolizumab (CIM331), a humanized antibody against interleukin-31 receptor A, in the treatment of atopic dermatitis. METHODS: In this phase 2, randomized, double-blind, placebo-controlled, 12-week trial, we assigned adults with moderate-to-severe atopic dermatitis that was inadequately controlled by topical treatments to receive subcutaneous nemolizumab (at a dose of 0.1 mg, 0.5 mg, or 2.0 mg per kilogram of body weight) or placebo every 4 weeks or an exploratory dose of 2.0 mg of nemolizumab per kilogram every 8 weeks. The primary end point was the percentage improvement from baseline in the score on the pruritus visual-analogue scale (on which a negative change indicates improvement) at week 12. Secondary end points included changes in the score on the Eczema Area and Severity Index (EASI, on which a negative change indicates improvement), and body-surface area of atopic dermatitis. RESULTS: Of 264 patients who underwent randomization, 216 (82%) completed the study. At week 12, among the patients who received nemolizumab every 4 weeks, changes on the pruritus visual-analogue scale were -43.7% in the 0.1-mg group, -59.8% in the 0.5-mg group, and -63.1% in the 2.0-mg group, versus -20.9% in the placebo group (P<0.01 for all comparisons). Changes on the EASI were -23.0%, -42.3%, and -40.9%, respectively, in the nemolizumab groups, versus -26.6% in the placebo group. Respective changes in body-surface area affected by atopic dermatitis were -7.5%, -20.0%, and -19.4% with nemolizumab, versus -15.7% with placebo. Among the patients receiving nemolizumab every 4 weeks, treatment discontinuations occurred in 9 of 53 patients (17%) in the 0.1-mg group, in 9 of 54 (17%) in the 0.5-mg group, and in 7 of 52 (13%) in the 2.0-mg group, versus in 9 of 53 (17%) in the placebo group. CONCLUSIONS: In this phase 2 trial, nemolizumab at all monthly doses significantly improved pruritus in patients with moderate-to-severe atopic dermatitis, which showed the efficacy of targeting interleukin-31 receptor A. The limited size and length of the trial preclude conclusions regarding adverse events. (Funded by Chugai Pharmaceutical; XCIMA ClinicalTrials.gov number, NCT01986933 .).

Nemolizumab in patients with moderate-to-severe atopic dermatitis: Randomized, phase II, long-term extension study.

BACKGROUND: Nemolizumab, an anti-IL-31 receptor A mAb, improved pruritus, dermatitis, and sleep in adults with moderate-to-severe atopic dermatitis that was inadequately controlled by topical treatments in a phase II, 12-week, randomized, double-blind, placebo-controlled study (part A; NCT01986933). OBJECTIVE: We sought to assess the long-term efficacy and safety of nemolizumab injected subcutaneously every 4 weeks (Q4W) or every 8 weeks (Q8W) in a 52-week, double-blind extension (part B). METHODS: During part B, patients continued the previous nemolizumab dose (0.1, 0.5, or 2.0 mg/kg Q4W or 2.0 mg/kg Q8W). Part B end points included percentage improvement from baseline in pruritus visual analog scale and dermatitis scores (including the Eczema Area and Severity Index). RESULTS: Overall, 216 of 264 patients completed part A, and 191 entered part B; 131 completed part B. In 153 patients randomized to nemolizumab in part A, improvement from baseline in pruritus visual analog scale score was maintained/increased from weeks 12 to 64, with greatest improvement in the 0.5-mg/kg Q4W group (percentage change from baseline at week 64: -73.0, -89.6, -74.7, and -79.1 in the 0.1-, 0.5-, and 2.0-mg/kg Q4W and 2.0-mg/kg Q8W groups, respectively). Improvement from baseline in dermatitis scores was also maintained/increased to week 64 (percentage change in Eczema Area and Severity Index score: -68.5, -75.8, -78.9, and -69.3 in the 0.1-, 0.5-, and 2.0-mg/kg Q4W and 2.0-mg/kg Q8W groups, respectively). Over 64 weeks, 83% to 89% had 1 or more adverse events, with no new safety concerns identified. CONCLUSION: Nemolizumab for up to 64 weeks was efficacious and overall well tolerated in patients with moderate-to-severe atopic dermatitis inadequately controlled by topical therapy.

[Diet in pathogenesis of acne vulgaris]. / Rola diety w patogenezie tradzika pospolitego.

Acne vulgaris is one of the most common dermatologic condition especially among adolescents. Acne is related to excess sebum production by sebaceous glands, inflammation both within and adjacent to the comedones, hyperproliferation of Propionibacterium acnes. Some of investigations show association between acne and diet. Milk increases the level of IGF-1 leading to the synthesis of androgen-mediated increases sebum production. Chocolate predispose to hyperglycemia and insulinemia which aggravate of acne vulgaris. High levels of omega-6 fatty acids have been associated with increase of acne in contrast to omega-3 fatty acids, which decrease inflammation. Food have huge impact on development and severity of acne and may exert beneficial effect in the treatment of this disorder.

[Atopic dermatitis - risk factors and treatment]. / Atopowe zapalenie skóry ­ czynniki ryzyka i leczenie.

Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by severe itching and eczematic skin lesions. In Poland from 1.5 to 2.5 million people suffer from AD. The pathophysiologic complexity and the wide spectrum of clinical phenotypes cause diagnostic and therapeutic problems and this is the basis for the division of the disease into subtypes. Heterogeneity of the disease is also confirmed in the study of the genotype of the disease. In relation with AZS more than 1000 loci in chromosomes were demonstrated. The roles of certain genes and the pathophysiology of lesions caused by their polymorphism were described. Wide spectrums of AD risk factors are: cigarette smoking, alcohol consumption during pregnancy, obesity and high and low birth weight. The quality of life in patients with AD is impaired, the disease disrupts family and professional relationships. Biological medical products are an example of an individual approach to the treatment of AD. It seems, individual approach to disease and treatment can be a successive solution to the problem.

Osteocyte Lacunae Density in Dentine-Induced Ectopic Bone.

The frequency of osteocytic lacunae, expressed as mean lacunae number per 1000 µm2 of measured bone, evaluated 65 days post intramuscular implantation of demineralized incisors is higher (1.10 ± 0.19) than in femoral (orthotopic) bone (0.91 ± 0.16). The surface of evaluated bones was measured by means of the "weight of bone picture". These results provide new data on the biology of ectopic bone.

[Influence of exogenous and endogenous factors on the course of psoriasis]. / Wplyw czynników endo- i egzogennych na przebieg luszczycy.

Psoriasis is a chronic, inflammatory disease, which symptoms appear mainly within the skin. Genetic and environmental factors are known to play a key role in etiopathogenesis of psoriasis. Therapy directed against psoriasis includes the topical and the systemic treatment. The immunotherapy (biologicals) is known to be relatively less harmful, due to action strictly against proinflammatory molecules, responsible in part for the progression of psoriasis. Because of substantial role of environmental factors in the etiopathogenesis of psoriasis, it is possible to get a clinical improvement of psoriatic lesions by modification of patients dietary habits and their lifestyle. Reduction of the calorific value of meals, the bodyweight reduction, the diet rich in unsaturated fats and antioxidants, likewise, abstinence and the reduction of stress level in everyday life, are known to have a positive effect on the course of psoriasis. It is stated that psoriatic patients are suffering from many other diseases e.g. cardiovascular, respiratory and hormonal diseases, whose treatment might exacerbate psoriasis. Thus, patients with psoriasis following the appropriate recommendations can greatly reduce disease progression.

[The importance of lactoferrin in bone regeneration]. / Znaczenie laktoferryny w regeneracji kosci.

Lactoferrin is an iron-binding protein secreted by mammary gland, thus present in milk and in colostrum, which are a cheap and easy to obtain sources of this protein. Lactoferrin is also present in specific granules of neutrophils. Lactoferrin is a multifunctional agent involved, among others in the immune response and in the regulation of bone metabolism. Lactoferrin actives of osteoblast proliferation and bone matrix secretion, and inhibits apoptosis of osteoblast and osteoclastogenesis. Lactoferrin administered to rodents accelerates bone healing and prevents bone loss induced by ovariectomy. Therefore the use of lactoferrin or milk whey in osteoporosis treatment and prevention is postulated.

Dupilumab in Adults With Moderate to Severe Atopic Dermatitis: A 5-Year Open-Label Extension Study.

Importance: Moderate to severe atopic dermatitis (AD) is a chronic inflammatory skin disease that often requires continuous long-term systemic management. Long-term safety and efficacy data for treatment options are critically important. Objective: To assess the safety and efficacy of dupilumab treatment for up to 5 years in adults with moderate to severe AD. Design, Setting, and Participants: The 5-year LIBERTY AD open-label extension study was conducted from September 2013 to June 2022 at 550 sites in 28 countries. The study enrolled adult patients with moderate to severe AD who had participated in previous dupilumab clinical trials. Data were analyzed from August 2022 to February 2023. Exposures: At enrollment, patients initiated a regimen of subcutaneous dupilumab, 200 mg, weekly (400-mg loading dose). The regimen was amended in June 2014 to dupilumab, 300 mg, weekly (600-mg loading dose) based on a dose-ranging study and again in November 2019 to dupilumab, 300 mg, every 2 weeks to align with the regulatory regimen approvals. Main Outcomes and Measures: The primary end points were the incidence and rate of treatment-emergent adverse events (TEAEs). Key secondary end points included incidence and rate of serious TEAEs and adverse events of special interest, proportion of patients achieving an Investigator's Global Assessment (IGA) score of 0 or 1 (clear or almost clear), and proportion of patients with 75% or more improvement in the Eczema Area and Severity Index (EASI) from the parent study baseline. Results: A total of 2677 patients were enrolled and treated in the open-label extension study; 1611 (60.2%) were male, and the mean (SD) age was 39.2 (13.4) years. A total of 334 patients (12.5%) completed treatment up to week 260. The most common reasons for withdrawal were due to regulatory approval of dupilumab in compliance with the study protocol (810 of 1380 [58.7%]), patient withdrawal (248 of 1380 [18.0%]), and adverse events (116 of 1380 [8.4%]). Exposure-adjusted rates of TEAEs were generally stable or declined throughout the study. Common TEAEs (incidence of 5% or greater) included nasopharyngitis, worsening AD, upper respiratory tract infection, conjunctivitis, conjunctivitis allergic, headache, oral herpes, and injection-site reaction. At week 260, 220 of 326 patients (67.5%) achieved an IGA score of 0 or 1 and 288 of 324 (88.9%) achieved 75% or greater improvement in the EASI. The mean (SD) EASI score was 16.39 (14.60) at baseline and 2.75 (5.62) at end of study. Conclusions and Relevance: In this study, there was sustained safety and efficacy of continuous long-term dupilumab treatment for adults with moderate to severe AD.

Fluvastatin influences hair color in C57BL/6 mice.

Our recent in vitro experiments suggest that fluvastatin may influence tyrosinase (key enzyme of melanogenesis) synthesis. The aim of the present study was to verify those findings in experiments, in vitro, in melanoma cell line, and in vivo, in mice. The expression of tyrosinase in B16F10 melanoma cell line, after induction of melanogenesis by UVB irradiation, was examined by Western blot analysis. Afterwards, the effect of fluvastatin on melanin synthesis in hair follicles of C57Bl/6 mice was investigated. The expression of tyrosinase was reduced in the presence of fluvastatin. In mice after anagen induction over the dorsal skin, gel containing fluvastatin in various concentrations was injected subcutaneously, while in part of control groups of mice, gel with placebo was injected. In addition, gel with fluvastatin was injected to four week-old mice (mice in first postnatal anagen) without anagen induction. In extension, injections of gel with fluvastatin or placebo were performed in mice without anagen induction (but after first postnatal anagen). In part of study group of mice (mice after anagen induction and injection of fluvastatin) regrowth of depigmented hair was observed, while in all control groups (mice after injection of placebo), such hair depigmentation over the skin area was not found. In conclusion, this study, for the first time, shows that fluvastatin might affect melanin synthesis in vivo.

Osteogenic efficiency of demineralized and lyophylized xenogeneic bone and syngeneic dentine implants in mice.

Intramuscular implantation of demineralized and lyophilized rat bone matrix and murine lower incisors into thigh muscles of BALB/c mice results in deposits of bone adjacent to the implants, a phenomenon termed as ectopic osteogenesis. The yield of induced bone does not critically depend on the mass of implanted matrices, and thus on the quantity of bone morphogenetic proteins (BMPs) present in the implants. A positive correlation between bone matrix implant weight and the yield of induced bone was observed only 28 days post grafting, i.e. when endochondreal osteogenesis is completed and bone resorption has not advanced. A more consistent yield of bone induction wasobserved in the case of demineralized tooth implants. It is postulated that chondro/osteoinduction by demineralized, lyophilized matrix implants is not determined by the range of BMPs presumably released in proportion to implant size, but is rather limited by the population of responsive host mesenchymal cells.

[Collagen based dressings in the treatment of wound healing]. / Opatrunki kolagenowe w gojeniu ran.

Collagen is the fundamental protein forming the connective tissues matrix, improves the ability of keratinocytes to migrate to sites that require rebuilding of the damaged epidermis, is one of the component of dressings used to accelerate wound healing. Because of the potential risk of the presence of pathogenic prions in bovine collagen, part of collagen dressings is formed on the basis of porcine collagen. Currently, a least of an immunogenic form of collagen is atelocollagen, which is subjected to enzyme-treated collagen, in which the terminal amino acids are removed from the collagen. It is assumed that in the near future atelocollagen will be used also as a carrier for drugs which support the healing processes.

Sclerostin, an osteocytes-derived bone-forming inhibitor.

Sclerostin is a recently identified glycoprotein expressed and synthesized by osteocytes. It is a powerful inhibitor of osteoblasts proliferation and differentiation. Sclerostin inhibits the Wnt signaling, the main trigger of osteoblasts activity. Osteocytes on response to a mechanical loading decrease the synthesis of sclerostin enabling in osteoblasts the Wnt signaling and promote their bone-forming activity. This explains why mechanical loading induces bone formation. Monoclonal antibodies directed against sclerostin reverses sclerostin induced bone catabolic effect and are promising tool in prevention and treatment of osteoporosis in human.

Adipose mesenchymal stem cells. Their characteristics and potential application in tissue repair.

Mesenchymal stem cells, derived from adipose tissue do not differ substantially from mesenchymal stem cells isolated from bone marrow stroma. They are able to differentiate in differentiating culture medium into various cell type of mesodermal lineage, but also into cells of ectodermal type. Their potency to differentiate toward osteogenic and adipogenic lineage is promising to be a ready source of cells for tissue regeneration.

Novel diagnostic and prognostic factors for the advanced melanoma based on the glycosylation-related changes studied by biophysical profiling methods.

Melanoma is a life-threatening disease due to the early onset of metastasis and frequent resistance to the applied treatment. For now, no single histological, immunohistochemical or serological biomarker was able to provide a precise predictive value for the aggressive behavior in melanoma patients. Thus, the search for quantifying methods allowing a simultaneous diagnosis and prognosis of melanoma patients is highly desirable. By investigating specific molecular interactions with some biosensor-based techniques, one can determine novel prognostic factors for this tumor. In our previous study, we have shown the possibility of a qualitative in vitro distinguishing the commercially available melanoma cells at different progression stages based on the measurements of the lectin Concanavalin A interacting with surface glycans present on cells. Here, we present the results of the quantitative diagnostic and prognostic study of both commercial and patient-derived melanoma cells based on the evaluation of two novel factors: lectin affinity and glycan viscoelastic index obtained from the quartz crystal microbalance with dissipation monitoring (QCM-D) measurements. Two approaches to the QCM-D measurements were applied, the first uses the ability of melanoma cells to grow as a monolayer of cells on the sensor (cell-based sensors), and the second shortens the time of the analysis (suspension cell based-sensors). The results were confirmed by the complementary label-free (atomic force microscopy, AFM; and surface plasmon resonance, SPR) and labeling (lectin-ELISA; and microscale thermophoresis, MST) techniques. This new approach provides additional quantitative diagnosis and a personalized prognosis which can be done simultaneously to the traditional histopathological analysis.

Dupilumab Provides Acceptable Safety and Sustained Efficacy for up to 4 Years in an Open-Label Study of Adults with Moderate-to-Severe Atopic Dermatitis.

BACKGROUND: Moderate-to-severe atopic dermatitis (AD) often requires long-term management with systemic therapies. OBJECTIVE: Our objective was to report the safety and efficacy of dupilumab treatment up to 4 years in adults with moderate-to-severe AD and efficacy in a subgroup of patients who transitioned from dupilumab once-weekly (qw) to administration every other week (q2w). METHODS: This interim analysis of the open-label extension study (NCT01949311) evaluated dupilumab 300 mg qw or q2w in adults previously enrolled in dupilumab trials for moderate-to-severe AD. Patients switched from qw to q2w following protocol amendment. The primary outcome was safety; efficacy was also assessed. RESULTS: Of 2677 patients enrolled and treated, 352 (13.1%) completed week 204 (end of efficacy assessments) and 202 (7.5%) completed safety follow-up through week 244. Self-reported compliance was 98.1%. Dupilumab's safety profile was consistent with previous reports. Common treatment-emergent adverse events (≥5%) included nasopharyngitis, AD, upper respiratory tract infection, oral herpes, conjunctivitis, injection-site reaction, and headache. At week 204, mean ± standard deviation (SD) Eczema Area and Severity Index was 2.46 ± 3.98, and mean percent change from parent study baseline (PSBL) was -91.07%; mean ± SD Pruritus Numerical Rating Scale score was 2.10 ± 1.83, and mean percent change from PSBL was -68.74%. Efficacy was maintained in patients (n = 226) who transitioned from qw to q2w dosing. Limitations of this study included its open-label design, the lack of control arm, and smaller subsets of patients at later timepoints and receiving the approved q2w regimen. CONCLUSION: These results support dupilumab as continuous long-term treatment for adults with moderate-to-severe AD; efficacy was sustained following transition from qw to q2w dosing. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT01949311.

Atopic dermatitis is a chronic skin disease associated with inflamed skin and intense itching. People with moderate-to-severe atopic dermatitis often need long-term treatment, but many available treatments do not have demonstrated long-term safety data. In multiple clinical trials, dupilumab treatment resulted in significant improvements in signs and symptoms of atopic dermatitis. This study examined the safety and efficacy of up to 4 years of dupilumab treatment in adults with moderate-to-severe atopic dermatitis, and whether dupilumab continued to be effective in patients who switched from receiving treatment each week to treatment every other week. To address these questions, we collected data from adults who received 300 milligrams of dupilumab every week or every other week. In this study, safety findings were consistent with the known dupilumab safety profile. Patients' signs and symptoms were evaluated before and during treatment with evaluation tools including the Eczema Area and Severity Index (EASI), which indicates the extent and severity of disease, and the Pruritus Numerical Rating Scale (NRS), which indicates the intensity of itching. Reductions of 91% in EASI scores and 69% in Pruritus NRS scores showed that the improvement in signs and symptoms persisted for 204 weeks (almost 4 years) of treatment, and these effects were sustained following the switch from weekly treatment to the approved every other week treatment with dupilumab. The safety and efficacy data presented here support the use of dupilumab as a continuous, long-term treatment for up to 4 years for adults with moderate-to-severe atopic dermatitis. Video abstract: What is the long-term safety and efficacy profile of dupilumab in adults with moderate-to-severeatopic dermatitis for up to 4 years? (MP4 102515 KB).

A Novel and Effective Method for Human Primary Skin Melanocytes and Metastatic Melanoma Cell Isolation.

The development of an effective method of melanocyte isolation and culture is necessary for basic and clinical studies concerning skin diseases, including skin pigmentation disorders and melanoma. In this paper, we describe a novel, non-enzymatic and effective method of skin melanocyte and metastatic melanoma cell isolation and culture (along with the spontaneous spheroid creation) from skin or lymph node explants. The method is based on the selective harvesting of melanocytes and melanoma cells emigrating from the cultured explants. Thereby, isolated cells retain their natural phenotypical features, such as expression of tyrosinase and Melan-A as well as melanin production and are not contaminated by keratinocytes and fibroblasts. Such melanocyte and melanoma cell cultures may be very useful for medical and cosmetology studies, including studies of antitumor therapies.